YAYINLAR

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.

BACKGROUND/AIM:

Selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) microspheres is also known as radioembolization and delivers high doses of radiation to hepatic tumors with minimum healthy liver exposure. The aim of this study was to present our preliminary experience in the role of liver directed radiotherapy with Y-90 microspheres for the treatment of unresectable hepatic metastases from neuroendocrine tumors (NET).

METHODS:

The results of SIRT in 10 patients (5 males, 5 females; mean age 48.7 years; age range 24-73 years) with metastatic liver disease from NETs during the period from April 2008 through August 2010 were reviewed. All patients had meticulous pre- and post-imaging studies as a part of their work-up procedure, as well as serologic tests of liver function to determine the extent of liver function damage. The patients who were eligible for SIRT had pretreatment visceral angiography to define and occlude non-target arteries.

RESULTS:

The mean +/- SD administered SIR-Spheres activity was 1.49 +/- 0.42 GBq (range 0.72-2.21 GBq) in all the patients. These treatments delivered a dose of 99.73 +/- 66.36 Gy (range 49-420.8 Gy) to the target tumors. The estimated dose to the lungs and normal liver was 4.45 +/- 1.95 Gy (range 2.4-8.5 Gy) and 26.73 +/- 14.19 Gy (range 5-58.9 Gy), respectively. Overall response rate of 90% and patient tolerance was satisfactory for most patients.

CONCLUSION:

From our limited experience, we can conclude that SIRT with Y-90 microspheres is a safe and efficacious treatment option for patients with liver metastasis of NET without any serious side effects.

PURPOSE:

A yolk sac tumor is a rare malignant tumor of germ cell origin. It most commonly arises from the testes and ovaries in young adults, but extragonadal sites of origin are reported in 10% to 15% of the cases. Yolk sac tumors are malignant, tend to recur locally, and may present with widespread metastases at the time of diagnosis. Involvement of the head and neck is uncommon. In this study, we present the case of a 23-year-old man presenting with mandibular and adjacent gingival metastasis of a mediasatinal yolk sac tumor. Thus, the patient has already undergone chemotherapy; no additional treatment was provided. In this case report, clinical and histopathologic features of the oral metastases of a yolk sac tumor were briefly discussed.

Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.

BACKGROUND:

Rapid hematological engraftment at autologous peripheral stem cell transplantation (APSCT) is a significant factor in reduction of early transplant-related complications and costs. For this reason, it is important to determine influences on hematological recovery.

METHODS:

This study was designed to evaluate factors affecting leukocyte and platelet engraftment times after high dose chemotherapy following APSCT. A total of 228 patients (131 males and 97 females) were enrolled.

RESULTS:

There were statistically significant differences between patients with CD34+ cell doses ≥ 2.5 x 10⁶/kg (n=180) and < 2.5 x 10⁶/kg (n=48), regarding leukocyte engraftment at 11 and 12 days, respectively (p<0.02), between G-CSF (n=167) and GM-CSF (n=61) posttransplant regarding median leukocyte engraftment times (p=0.005), and between with (n=75) or without (n=153) history of pretransplant radiotherapy for both leukocyte and platelet engraftment times (p<0.001).

CONCLUSIONS:

For leukocyte engraftment, a history of pretransplant radiotherapy, type of growth factor used and number of CD34+ cells infused, and for platelet engraftment, a history of pretransplant radiotherapy were found to be independent variables on multivariate analysis with the Cox regression method.

OBJECTIVE:

Meningeal carcinomatosis (MC) is a rare presentation of solid tumors, particularly breast cancer, lung cancer, and malignant melanoma. Recently, the incidence of MC has been reported to be increasing. It has a bad prognosis despite aggressive therapy. The usual clinical presentation is multifocal involvement of the neuraxis, with headache and radicular pain being the most common initial symptoms. The most frequent signs are motor deficits, altered mental status, and cranial nerve involvement. The treatment of MC remains controversial and no straightforward guidelines exist in the literature. MC from urinary bladder tumors is rare. In this case report, we present a 52-year-old male patient with meningeal metastasis from a primary urinary bladder carcinoma along with a review of the related literature. Free full text available at www.tumorionline.it

The aim of this study was to evaluate the potential relationship of microvascular growth patterns with survival in invasive breast carcinomas. Thirty-one invasive ductal carcinoma cases, followed up at least for 38 months, constituted our series. All cases had been studied for ER/PR and HER2/neu expression. Clinicopathological and survival data were obtained from the archives. Tissue sections from all cases were stained with CD34 antibody to highlight the microvascular network and to measure microvessel density (MVD). The cases were then classified according to the dominance of one of the five recognizable microvascular patterns. Cox proportional hazard regression model, Fisher’s exact test, and multivariate general linear model (GLM) were used to uncover the effects of the variables, such as nodal status, distant metastasis, angiogenic patterns, and MVD, on survival. There was an association between only one of the microvascular patterns and aggressive clinical course. Increased blood-filled capillaries with some clustering in the tumor might be a predictor of aggressive biological behavior in invasive breast carcinomas. Similar studies investigating larger series are needed before a generalized conclusion can be made.

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.

PURPOSE:

A 29-year-old woman with left pleural effusion and a mass in anterior mediastinum was admitted. Transthoracic needle aspiration from the mass revealed findings consistent with nodular sclerosis variety of Hodgkin’s disease. The patient was in remission after six cycles of ABVD followed by mediastinal radiotherapy. Ten months later CT scan showed three hypodense masses in the right kidney. Ultrasound guided renal biopsy revealed diffuse large B cell lymphoma. Retrospective re-evaluation of the archival specimens of the mediastinal mass was also consistent with diffuse large B cell lymphoma. After induction chemotherapy (four cycles of DHAP) she underwent high dose chemotherapy (BEAM) and autologous peripheral blood stem cell transplantation. She is still in remission for 7 years after transplantation. In conclusion, renal involvement during advanced lymphoma is quite common but isolated renal relapse in NHL is a rare situation. Although renal infiltration generally shows a poor prognosis, long-term survival may be achieved with high dose chemotherapy and autologous peripheral blood stem cell transplantation.

PURPOSE:

OBJECTIVE:

To report an unusual paraneoplastic syndrome, amyotrophic lateral sclerosis, associated with renal cell carcinoma.

CASE PRESENTATION AND INTERVENTION:

A 59-year-old man presented with muscle weakness and fasciculations in the upper extremities. Neurological examination showed that the fasciculations arose spontaneously in the upper limbs. Electrodiagnostic studies revealed an active neurogenic disorder. The patient was diagnosed with a motor neuron disease mimicking amyotrophic lateral sclerosis. Urine analysis revealed microscopic hematuria. Abdominal computerized tomography scans showed a 9.5 x 8 cm renal mass in the lower pole of the right kidney. Curative right radical nephrectomy was performed. Pathologic examination showed a clear cell adenocarcinoma. After nephrectomy, the muscle weakness and fasciculations disappeared spontaneously within 2 months. The patient was disease-free for 58 months after right radical nephrectomy. He complained of muscle weakness and fasciculation at the last follow-up again. Physical examination revealed fasciculation in the upper limbs. Abdominal tomography showed a 22 x 20 mm solid mass in the lower pole of the left kidney. Kidney-saving surgery was performed and the diagnosis of renal cell carcinoma was confirmed pathologically. Following surgery, fasciculations completely disappeared and muscle weakness diminished within 3 months.

CONCLUSION:

This case highlights motor neuron disease as a rare paraneoplastic syndrome in association with renal cell carcinoma and resolution after removal of the tumor.

The outcome of Ewing’s sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing’s sarcoma patients that received long-term treatment protocol. Twenty-five patients (22 males, 3 females) with poor prognostic features were treated according to long-term Ewing’s sarcoma protocol. Central-axis localization, inadequacy or unavailability of surgical resection, older than 15 years of age, are accepted as high-risk factors. The median age of patients was 23 years (range, 18-55). The tumor localization was pelvis (9), femur (1), tibia (1), fibula (1), maxilla (1), clavicle (1), vertebrae (5), metatarse (1), and ribs (5). Neoadjuvant chemotherapy was applied between weeks 0 and 6, local therapy on week 9, and adjuvant maintenance chemotherapy between weeks 11 and 41. All patients received neoadjuvant and adjuvant maintenance chemotherapy. Local therapy consisted of radiotherapy (32%), surgery alone (12%), or surgery and radiotherapy (56%). The median total treatment period was 10 months. The median follow-up was 25 months (range, 7-89). Three-year cumulative OS and DFS rates were 43% (95% CI, 28.5-57.85) and 40% (95% CI 23.63-52.19), respectively. The most common grade III/IV toxicities observed during the treatment protocol were neutropenia (16%) and gastrointestinal toxicities (16%). Our study indicated that long-term multiagent combination chemotherapy may result in better outcome in adult high-risk patients undergoing adequate surgical resection of the tumor and local radiotherapy. Further randomized studies are needed to assess the efficacy of this treatment protocol in patients with adequate surgical margins.

We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

SCT is a curative approach using chemo-, radio- and immunotherapy for malignant and non-malignant hematological disorders. The European Group for Blood and Marrow Transplantation (EBMT) has been collecting yearly data on a survey basis since 1990. The variables within the survey are limited to detailed indications, number of patients, transplant type, stem cell source, type of conditioning regimen and donor type. The transplant rates in certain indications, patterns of stem cell source selection and donor availability and alternative donor use were analyzed in detail. The Turkish transplant registry data within EBMT-European Activity Survey (EBMT-EAS) were delivered by the EBMT Activity Survey Office. We compared the national data with the international EBMT-EAS data pool.

Scleromyxedema is a rare disorder characterized by mucin deposits in the dermis and monoclonal gammopathy. No definitive treatment of this condition has been described to date. We present the case of a 38-year-old male patient with scleromyxedema who underwent double consecutive autologous peripheral stem cell transplantations and received immunoglobulin, thalidomide, and bortezomib. This resulted in considerable clinical and pathologic amelioration of the patient’s condition. However, 3 years after the second transplant, the patient relapsed and manifested the same skin lesions evident at his initial presentation.

OBJECTIVE:

To compare acute renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide (TBI-Cy) and Ifosfamide, Carboplatin, and Etoposide (ICE).

METHODS:

Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-seven patients received ICE regimen with 12 g/m2; 1.2 g/m2; and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI (6 fractions twice daily in 3 consecutive days) and 60 mg/m2/day cyclophosphamide for 2 days.

RESULTS:

Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity (23.4%) in the ICE group while one patient (4.8%) in the TBI-Cy group developed nephrotoxicity (p=0.06). Five out of 11 patients developing nephrotoxicity in ICE group required hemodialysis and subsequently 4 (8.5%) of them died. In contrast, one patient (4.8%) died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm.

CONCLUSION:

This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation.

OBJECTIVE:

To compare acute renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide (TBI-Cy) and Ifosfamide, Carboplatin, and Etoposide (ICE).

METHODS:

Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-seven patients received ICE regimen with 12 g/m2; 1.2 g/m2; and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI (6 fractions twice daily in 3 consecutive days) and 60 mg/m2/day cyclophosphamide for 2 days.

RESULTS:

Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity (23.4%) in the ICE group while one patient (4.8%) in the TBI-Cy group developed nephrotoxicity (p=0.06). Five out of 11 patients developing nephrotoxicity in ICE group required hemodialysis and subsequently 4 (8.5%) of them died. In contrast, one patient (4.8%) died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm.

CONCLUSION:

This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation.

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.

Allogeneic transplantation of hematopoietic cells from an HLA-compatible donor has been used to treat hematologic malignancies. Allogeneic transplantation not only replaces the marrow affected by the disease, but exerts an immune graft-versus-tumor (GVT) effect mediated by donor lymphocytes. The development of nonmyeloablative conditioning regimens before allogeneic transplantation has allowed this therapy to be used in elderly and disabled patients. An allogeneic GVT effect is observed in a proportion of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allogeneic transplantation. In general, the tumor response is associated with the development of acute and chronic graft-versus-host disease. Further improvements will depend on the identification of the antigen targets of GVT, and on reduction of the toxicity of the procedure. Targeted therapies may complement the immune effect of allogeneic transplantation. We present updated results from the literature and data recently placed on file at the European Bone Marrow Transplantation Solid Tumors Working Party.

AIMS AND BACKGROUND:

The role of high-dose chemotherapy in breast cancer has not been fully defined. It has been concluded that new trials should focus on defining potential subgroups that are more likely to benefit from high-dose chemotherapy. We compared survival differences in patients receiving human granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte colony stimulating factor (GM-CSF) after high-dose chemotherapy with stem cell support.

METHODS:

High-risk non-metastatic breast cancer patients (axillary lymph node involvement more than 8) aged 16 to 65 years and with a performance status < or = 1 underwent high-dose chemotherapy with autograft. Written informed consent was obtained from every patient, and the study was approved by the local ethics committee.

RESULTS:

For 54 eligible women, the median follow-up was 41.4 months. The five-year disease-free survival was 45.7%. The five-year projected overall survival rate was 53.9%. Among them, patients who received GM-CSF (n = 12) posttransplant lived longer than the patients who received G-CSF (n = 15) (five year survival rates, 46.6% vs 75%, P < 0.050). The patients who received GM-CSF posttransplant had fewer relapses (5 vs 9). However, between the two groups there was no statistically significant difference regarding disease-free survival rates calculated with the Kaplan-Meier method (58.8% vs 40%; P = 0.121).

CONCLUSIONS:

Patients receiving GM-CSF posttransplant lived longer and they had fewer relapses than those who received G-CSF. This result merits consideration. The antitumor activity of GM-CSF should be investigated further in prospective randomized trials.

Hematopoetic stem cell transplantation, even from an HLA 6/6 identical family member is associated with an increased frequency of complication in fanconi anemia (FA). The increased susceptibility for chromosomal breaks has been suggested as a contributory factor for increased risk of toxicity, graft versus host disease (GVHD) and increased incidence of post-transplant solid tumors. Therefore, non-irradiation based preparative regimens usually containing fludarabine and T-cell depletion of HLA geno-identical bone marrow cells have increasingly been used in patients with FA. Here, we report three children with FA who underwent CD-34 selected HSCT from HLA-identical family donors with reduced intensity fludarabine-based regimen.

Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n=16), osteopetrosis (n=2), MDS (n=1), amegakaryocytic thrombocytopenia (n=1), and aplastic anemia (n=1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 x 10(6) G-CSF-mobilized peripheral CD34(+) progenitor cells and a median of 4.19 x 10(4) T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B- SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation.

Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n=16), osteopetrosis (n=2), MDS (n=1), amegakaryocytic thrombocytopenia (n=1), and aplastic anemia (n=1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 x 10(6) G-CSF-mobilized peripheral CD34(+) progenitor cells and a median of 4.19 x 10(4) T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B- SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation.

BACKGROUND:

The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors.

AIMS:

The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002.

SETTINGS AND DESIGN:

Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group.

MATERIALS AND METHODS:

Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients’ outcome.

STATISTICAL ANALYSIS:

Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis.

RESULTS:

Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% (P<0.001) and disease-free survival rates were 83%, 34% and 7% (P<0.001) in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor (P<0.001), the initial beta-HCG level (p:0.0048), the presence of yolk sac and choriocarcinoma components in tumor (p:0.003 and p:0.004), relapse sites of tumor (lung versus other than lung) (p:0.003), persistent elevation of serum tumor markers (P<0.001) were significant prognostic factors in univariate analysis. However, in multivariate analysis, only the localization site of tumor (p:0.049) and the relapse site (p:0.003) were found statistically significant.

CONCLUSIONS:

This retrospective study revealed that in advanced stage of nonseminomatous germ cell tumors, the outcome is essentially related with the localization site of the tumor and the relapse site.

BACKGROUND:

[corrected] The effectiveness of chemotherapy is limited by the emergence of multidrug resistance (MDR). MDR is caused by the activity of various ATP binding cassette (ABC) transporters that pump anticancer drugs out of the cells in an ATP-dependent manner. Additionally some other cellular mechanisms of MDR have been reported. The purpose of this study was to investigate mechanisms of MDR in drug resistant MCF-7 cell lines and to modulate P-glycoprotein (P-gp) and MRP1-based MDR.

MATERIALS AND METHODS:

Paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), doxorubicin (MCF-7/Dox) and vincristine (MCF-7/Vinc) resistant sublines were developed from the parent MCF-7 cell line (MCF-7/S) by stepwise selection in dose increments over two years. Flow cytometry, MTT cytotoxicity assay, RT-PCR, caspase-3 activity assay and checkerboard combination assay were performed to investigate the degree of resistance developed in sublines and to reverse drug resistance phenotype.

RESULTS:

The flow cytometry histograms of drug accumulation assays demonstrated that the drug-resistant cell lines are P-gp and MRPI positive. RT-PCR results showed that the resistant sublines express both MDR1 and MRP1 genes. Resistance indices of each subline to each anticancer drug were determined using the MTT cytotoxicity assay and it was found that all the sublines were resistant to their respective agents. Caspase-3 activities of the cell lines were also determined. Caspase-3 activity is an important indicator of apoptosis in the cell. The reversal of MDR was attempted by two cinnamylidene ketone and two organosilicon compounds. The results indicated that these compounds modulated P-gp effectively, but they were not very effective at reversing MRP1 activity in the MCF-7 sublines. Four selective anticancer drugs (paclitaxel, docetaxel, doxorubicin and vincristine) and four synthetic MDR modulators [2-(2-methoxycinnamylidene) indan-1-one (cinnamylidene-1), 2-(2- methoxycinnamylidene)-3, 4-dihydro-2H-naphthelen-1-one) (cinnamylidene-2), ALIS 409 and ALIS 421] were applied to the sublines in combination. The fractional inhibitory indices illustrated that combined applications of cinnamylidene ketones and organosilicon compounds with paclitaxel, docetaxel or vincristine exerted significant antiproliferative effects on the resistant sublines.

CONCLUSION:

This report demonstrates the development of rational models for drug resistance MCF-7 cell lines and reversal of acquired drug resistance.

PURPOSE/OBJECTIVES:

To determine whether a relationship exists between quality of life (QOL) and the sociodemographic characteristics of gender, age, marital status, educational level, occupation, and level of income in patients with cancer in Turkey.

DESIGN:

Exploratory study using a convenience sample.

SETTING:

Five hospitals in the capital city of Turkey.

SAMPLE:

620 patients with cancer (44 inpatients and 576 outpatients).

METHODS:

The study was carried out using face-to-face interviews. A questionnaire was used as a tool for collecting data on the sociodemographic characteristics of patients, and the Rolls-Royce Quality-of-Life Scale was employed to measure QOL.

MAIN RESEARCH VARIABLES:

Gender, age, marital status, educational level, occupation, level of income, and QOL.

FINDINGS:

Men, older adults, widowed spouses, patients with lower levels of education, housewives, and those with lower income had lower QOL scores.

CONCLUSIONS:

Considering the results and giving the groups referred to in the study priority in the planning of patient care would be useful.

IMPLICATIONS FOR NURSING:

In the field of nursing in Turkey, a limited number of studies have examined the relationship between the sociodemographic characteristics of patients with cancer and QOL. The results will help nurses assess patient needs and engage in nursing interventions that are appropriate to the needs.

PURPOSE/OBJECTIVES:

To determine whether a relationship exists between quality of life (QOL) and the sociodemographic characteristics of gender, age, marital status, educational level, occupation, and level of income in patients with cancer in Turkey.

DESIGN:

Exploratory study using a convenience sample.

SETTING:

Five hospitals in the capital city of Turkey.

SAMPLE:

620 patients with cancer (44 inpatients and 576 outpatients).

METHODS:

The study was carried out using face-to-face interviews. A questionnaire was used as a tool for collecting data on the sociodemographic characteristics of patients, and the Rolls-Royce Quality-of-Life Scale was employed to measure QOL.

MAIN RESEARCH VARIABLES:

Gender, age, marital status, educational level, occupation, level of income, and QOL.

FINDINGS:

Men, older adults, widowed spouses, patients with lower levels of education, housewives, and those with lower income had lower QOL scores.

CONCLUSIONS:

Considering the results and giving the groups referred to in the study priority in the planning of patient care would be useful.

IMPLICATIONS FOR NURSING:

In the field of nursing in Turkey, a limited number of studies have examined the relationship between the sociodemographic characteristics of patients with cancer and QOL. The results will help nurses assess patient needs and engage in nursing interventions that are appropriate to the needs.

Today, chronic diseases have increased importance. Cancer, for which 10 million new cases are diagnosed around the world each year, is in the lead of such diseases. This study included military personnel with cancer who applied to the Department of Medical Oncology, Gülhane Military Medical Academy, in the period between 1998 and 2003, and it aims to describe some sociodemographic and diagnostic characteristics of the patients. The total number of cases was 938, which included both active duty and retired military personnel with diagnoses of cancer who were given medical care between 1998 and 2003 in the Department of Medical Oncology. For the study group, the five most common diagnoses were lung cancer, colorectal cancer, testicular cancer, non-Hodgkin’s lymphoma, and Hodgkin’s disease. Although the first three diagnoses among officers were lung cancer, testicular cancer, and Hodgkin’s disease, those among retired officers were colorectal cancer, lung cancer, and prostate cancer. Among noncommissioned officers, the first three diagnoses were colorectal cancer, testicular cancer, and Hodgkin’s disease for active duty patients and lung cancer, colorectal cancer, and gastric cancer for retired patients. In the group of privates, testicular cancer, Hodgkin’s disease, and non-Hodgkin’s lymphoma were the first three diagnoses. When we consider the characteristics of cancers, such as high costs of treatment, loss of manpower, and high mortality rates, prevention of cancers and early diagnosis are very important. Because the frequent types of cancers differed for groups according to age and occupation, those characteristics should be considered when cancer screening programs are being developed for the Armed Forces.

A 38-year-old female with chronic myeloid leukemia underwent an allogeneic bone marrow transplantation from her full-matched brother. Eleven months later, she readmitted with an acute leukemia that was shown to be of donor origin. The patient never achieved a remission even after chemotherapies with cytarabine and mitoxantrone, donor lymphocyte infusion, and second allogeneic peripheral blood stem cell transplantation. Donor cell leukemia (DCL) is sometimes misdiagnosed as relapse by clinicians and the real incidence may be higher than expected. Cytogenetic and molecular techniques may be helpful to clarify the issue of the leukemia. The current case is another case of DCL reported in the literature after an allogeneic transplant for a kind of leukemia.

This study was designed to measure the frequency at which Turkish patients with cancer resort to complementary and alternative medicine (CAM). A total of 704 patients referred to the Gülhane Military Medical Academy and Ankara Numune Training Hospital between September 2002 and January 2003 were asked about the CAM therapies they used. Of these, 276 patients (39.2%) had used CAM. Gender, marital status, educational status, age, financial status, severity of pain, history of cancer in the family, and their own ideas concerning CAM therapies were found to be correlated with the frequency of resorting to CAM. Resorting to CAM may lead to delayed diagnosis and treatment, adverse drug interactions, treatment withdrawal, and disease progression. Therefore, it is very important to inform patients about these potential dangers. Further studies are needed to clarify the reasons that lead patients to resort to CAM.

Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein expression in normal tissues. It was suggested that this might have an advantage in cancer chemotherapy by resulting in a low drug-resistance phenotype. The frequencies of these SNPs were studied in 45 acute leukemia patients (25 of which were primary refractory and 20 of which were drug-sensitive) and 17 healthy individuals, forming a Turkish population of 62 individuals. In the first part of the study, these polymorphisms were compared with other populations. Marked differences were apparent between African and Turkish populations for the C3435T polymorphism. On the other hand, similarities were found between other Caucasian/Asian and Turkish populations (P < 0.001). However, for the G2677T polymorphism, the Turkish population is different than Japanese and German populations (P < 0.001). For the T-129C polymorphism, all individuals in the studied population were homozygous for the T/T genotype. In the second part of this study, drug-resistant and drug-sensitive acute leukemia patients were compared for these SNPs. These polymorphisms did not seem to have a significant effect on P-glycoprotein-mediated drug resistance in the patients studied.

Primary cutaneous B-cell lymphomas (PCBCL) are rare and constitute 5-10% of all cutaneous lymphomas. In patients with PCBCL presenting with solitary or localized skin lesions, radiotherapy is the preferred treatment. Two patients who were treated with 4 MeV electrons, both obtained remission for 51 months. Unfortunately, at the last visit one patient relapsed on the border of the radiotherapy field and was re-treated with a generous irradiation field in 2004. Complete response was obtained again. Thus, for localized PCBCL, radiotherapy alone is an effective treatment.

Treatment of non-Hodgkin’s lymphoma with the CHOP regimen consists of intravenous cyclophosphamide 750 mg/m2 (day 1), intravenous doxorubicin 50 mg/m2 (day 1), intravenous vincristine 1.4 mg/m2 (day 1), and oral prednisone 100 mg (days 1-5). This regimen is administered in cycles of approximately 3 weeks; a total course of treatment consists of six cycles. We report the case of a 23-year-old woman with diffuse large-cell lymphoma who received an accidental overdose of this chemotherapeutic regimen. The first cycle of her CHOP regimen was initiated (day 1) in our outpatient unit; she was then discharged home. Unfortunately, the patient went to another hospital located in the small city where she lived, and all remaining doses of the total course of treatment were administered over the next 5 consecutive days, with no interruption in therapy. She had received cumulative doses of cyclophosphamide 6000 mg, doxorubicin 420 mg, and vincristine 12 mg. She was transferred to our hospital after she developed pancytopenia, fever, and ileus. With the help of intensive supportive care and symptomatic treatment, the patient recovered and was discharged home after a hospital stay of 25 days. After 56 months, she was free of disease and treatment-related toxicities. Only experienced clinicians should administer chemotherapy, and thorough records must be kept to document the chemotherapy administered, dosages, dates of administration, the procedure used, and the schedule of cycles administered.

BACKGROUND:

The primary and secondary objectives of the current study were to improve the > or = 90% tumor necrosis rate and assess the toxicity profile of the neoadjuvant high-dose chemotherapy (HDC) regimen, respectively.

METHODS:

Twenty-two patients with AJCC Stage IIB high-grade osteosarcoma were included in the current study. Two cycles of an induction chemotherapy regimen including cisplatin, doxorubicin, and ifosfamide followed by HDC and autologous peripheral blood stem cell support or transplantation (APBSCT) were given. After engraftment was achieved, the patients underwent limb-sparing surgery (LSS) followed by three to six cycles of postoperative chemotherapy depending on the tumor necrosis rate.

RESULTS:

The median follow-up, the total duration of treatment, and the time to surgery were 23.7 months, 5.96 months, and 3.03 months, respectively. The necrosis rate was at least 90% in 82% of the cases. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 83% and 70%, respectively. Leukopenia, anemia, thrombocytopenia, nausea and emesis, and mucositis were the most frequent Grade 3 and Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) of induction, high-dose, and adjuvant chemotherapies. At the time of last follow-up, no patient had died of chemotherapeutic toxicity. LSS was performed in all patients. Surgery-related complications were reported in 3 of 22 patients. Functional scoring results were excellent in eight patients, good in nine patients, fair in two patients, and poor in three patients.

CONCLUSIONS:

The results of the current Phase II study suggest that neoadjuvant HDC provides a greater than 90% necrosis rate with acceptable toxicity. A short duration of therapy and the feasibility of LSS in all patients are additional advantages of this approach.

This prospective study was carried out in healthy donors and patients. The performance of the CliniMACS was evaluated with the comparison of the numbers of total nucleated cell (TNC) within and over the capacity of the normal scale column. In addition, large vs. normal scale column and manual vs. automated washing systems were also compared. A total of 44 selections were done. Eighteen normal scale selections were done with initial TNC numbers over 6 x 10(10) and 14 selections were performed below this number. None of the cases had CD34+ cell numbers over the capacity. Flow cytometry was used to check each separation performance for purity and recovery of CD34+ cells along with T- and B-cell depletion level parameters. All healthy donors had significantly better mean purity and recovery of CD34+ cells, and T- and B-cell depletion status than that of patients with values 95 vs. 85%, P: 0.006; 77 vs. 58%, P: 0.004; 4.55 log vs. 4.06 log, P: 0.004; 3.19 log vs. 2.63 log, P: 0.01, respectively. However, the performance of the system was not dependent on using the normal or large-scale column; automated or manual washing systems; and initial TNC numbers above (>6 x 10(10), range: 7.05-21.84 x 10(10), mean: 12.32 x 10(10)) or within (<6 x 10(10), range: 0.86-5.89 x 10(10), mean: 4.15 x 10(10)) the column capacity. In conclusion, the performance of the CliniMACS is more efficient in healthy donors than in patients. However, the performance of the system did not change as long as the numbers of CD34+ cells (range: 0.34-5.87 x 10(8)) were not exceeding the column capacity despite that more than 6 x 10(10) TNCs were used.

Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.

Chemotherapy and radiation therapy are associated with increased formation of reactive oxygen species and depletion of critical plasma and tissue antioxidants. In patients undergoing high-dose chemotherapy, the plasma antioxidant concentration has been shown to decrease. However, these studies in which the oxidative stress status were investigated have a small number of patients and they are heterogeneous. In this study, the changes in certain trace elements together with oxidative stress parameters were investigated in 36 patients who had undergone autologous stem cell transplantation because of solid and hematological malignancies. Blood samples of the patients were examined before the high-dose chemotherapy (baseline), before stem cell transplantation (day -1), and after stem cell transplantation on day 1, 3, and 6. Erythrocyte zinc, silver, and iron levels were measured by atomic absorption spectrophotometry; malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured by UV-vis spectrophotometry. After high-dose chemotherapy, significant increases in the levels of MDA, GSH-Px, and SOD were observed. On the other hand, Cu levels remained the same while the levels of erythrocyte Zn and Fe were increased. Significant correlation was observed among MDA, GSH-Px, and SOD (p<0.05). High-dose chemotherapy gives rise to an increase in the oxidative stress and the reactive oxygen species. Standard parenteral nutrition protocols were found to be insufficient to lower this stress.

The purpose of this study is to report on the dose homogeneity in total body irradiated patients undergoing Bone Marrow Transplantation (BMT), and carcinogenic risk in surviving patients. Between 1987 and 2001, 105 patients received hyperfractionated (6 fractions in 3 days) 12 Gy Total Body Irradiation (TBI) in our institution with lateral opposed fields. All the patients had measurements with thermoluminiscence dosimetry (TLD100) placed on seven bilateral body sites in vivo, controlled by the randophantom measurements to verify reasonable dose homogeneity achievement. The comorbid effects in the whole TBI conditioning group with at least three months post BMT follow-up were noted and surviving patients who had a minimum 5-year and maximum 14-year follow-up (median 7.8 years) have been evaluated for carcinogenic radiation risk on the basis of tissue weighting factors as defined by ICRP 60. Reasonable dose homogeneity by lateral opposed beam TBI has been obtained in all 105 patients in whom lateral TLD100 measurement means were within +5% of the planned doses. Calculated carcinogenesis risk factor was 11.34% for males and 12.40% for females, and no second-cancer has been detected whilst radiation-induced 5 cataracts and 10 interstitial pneumonia comorbidities were noted. Dose homogenization can be well achieved for hyperfractionated lateral-beam TBI with acceptable comorbidities and estimated second-cancer risk is significant but relatively low compared to the risk from the clinical indications for TBI.

In the past, variable results were reported for single daily and two divided daily doses of granulocyte colony-stimulating factor (G-CSF) in stem cell collection where no study exists investigating the effect of body mass index (BMI) on mobilization. The numbers of CD34(+) cells collected were compared in 86 patients with solid or hematological malignancies receiving either single daily (14 mug/kg/day) G-CSF (filgrastim) as group I (n=36) or two divided doses of G-CSF daily (2 x 7 mug/kg/day) as group II (n = 50). Both groups were divided into subgroups according to their BMI as group a (BMI </=25 kg/m(2)) and group b (BMI >25 kg/m(2)). Two groups were similar in terms of BMI, gender, and disease characteristics. All patients have received G-CSF as a single or two divided doses subcutaneously and aphereses have been done on the 5th day. No significant difference in numbers of CD34(+) cells between groups Ia and Ib, groups IIa and IIb, and groups Ia and IIa was found. On the other hand, the mean ratio and the number of CD34(+) cells in group Ib were significantly higher than those of group IIb (0.58 +/- 0.06% vs. 0.37 +/- 0.26%, P = 0.01 and 3.67 +/- 0.65 x 10(4)/kg/ml vs. 1.92 +/- 0.37 x 10(4)/kg/ml, P= 0.02). In conclusion, in patients with BMI >25 kg/m(2), once daily G-CSF compared to split dose administration induces a greater number of CD34(+) stem cell mobilization, which suggests the presence of a different pharmacokinetics in obese patients.

In this prospective study, the effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on immunological reconstitution after autologous peripheral blood stem cell transplantation (PBSCT) were investigated for 6 months. Thirty-five patients received G-CSF 5 microg/kg per day and 26 patients received GM-CSF SC 5 microg/kg per day from day 1 to leukocyte engraftment (>1000 per mm3). Peripheral blood samples were obtained on 14, 28, 100, and 180 days after transplantation for immunological evaluation. CD3+, CD4+, CD8+, CD19+, and CD56+ cells were analysed by flow cytometry. Immunoglobulin levels (IgG, IgA, and IgM) and complement levels (C3c and C4) were measured by nephelometry. Both G-CSF and GM-CSF groups were comparable with respect to age, sex, the period from diagnosis to transplantation, total nucleated cells infused, the number of CD34+ cells, conditioning regimens (TBI and non-TBI), and post-transplant infection. CD3+ and CD8+ cells on day 14 following autologous PBSCT + G-CSF were significantly higher than following autologous PBSCT + GM-CSF (p = 0.008 and p = 0.021, respectively). The number of CD4 cells and the CD4/CD8 ratio were not different at several time points between the two groups. CD19+, CD56+ cells and immunoglobulin levels showed a faster recovery pattern in the autologous PBSCT + G-CSF group. The effect of G-CSF on immune reconstitution after autologous PBSCT is more prominent than that of GM-CSF. The possible role of haematopoietic growth factor on immune recovery and its clinical importance should be investigated in further studies.

AIM AND BACKGROUND:

To evaluate the alterations of serum leptin levels during stem cell transplantation and its possible role in engraftment. Thirty-two patients (19 male, 13 female) with various hematological and solid tumors and 28 healthy subjects (15 male, 13 female) as a control group were enrolled in the study.

METHODS:

Serum leptin levels were measured on the day before administering G-CSF, at the time of leukapheresis harvest, on day +1st and +7th after transplantation and on the day of leukocyte engraftment.

RESULTS:

There was no significant difference in serum leptin levels between patients (mean +/- SEM, 11.62 +/- 2.75 ng/ml) before transplantation and control groups (9.79 +/- 1.73 ng/ml). Pre-G-CSF (baseline) level of serum leptin (11.62 +/- 2.75 ng/ml) was significantly decreased to 7.73 +/- 2.02 ng/ml at the time of apheresis harvest (P = 0.0029). Later, serum leptin levels increased to 16.75 +/- 3.26 ng/ml on day +1 after transplantation (P < 0.0001). Subsequently serum leptin levels both on day +7th posttransplant (12.11 +/- 2.17 ng/ml) and leukocyte engraftment day (9.26 +/- 1.50 ng/ml) were gradually decreased. There was no correlation between the serum leptin levels and the leukocyte or platelet engraftment.

CONCLUSION:

The present study concludes that serum leptin level does not change remarkably during peripheral blood stem cell transplantation and no association exists between circulating leptin levels and the onset of engraftment suggesting that circulating serum leptin does not have a significant direct influence on engraftment.

BACKGROUND:

Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials.

METHODS:

The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels.

RESULTS:

Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37+/-3.7 vs 26+/-1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m(2), P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001).

CONCLUSIONS:

The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.

BACKGROUND:

The primary aim of the study was to compare two different dose levels of megestrol acetate, administered for cancer-related anorexia and cachexia for 3 months.

METHODS:

From August 1996 to December 2000, 119 patients with advanced non-small cell lung cancer were randomized to take 160 mg/day or 320 mg/day of megestrol acetate for 3 months at the Gülhane Military Medicine Academy of Ankara, Turkey. Patients were controlled at biweekly periods.

RESULTS:

There were 59 patients in the single dose arm (group 1) and 60 patients in the twice a day dose arm (group 2). The mean percentages of weight loss were 16.9% and 16.7% in group 1 and 2, respectively. In the first and the second month of weight gain, there were no significant differences in the two groups (P = 0.23 and P = 0.11). In the third month, weight gain was significantly higher in group 2 than in group 1 (P = 0.038). Toxicity was similar for both dose levels.

CONCLUSIONS:

Megestrol acetate can be safely and effectively given to patients with advanced non-small cell lung cancer. Although lower doses of megestrol acetate can be effective for anorexia and cachexia, the higher dose level seems to be more efficient.

PURPOSE:

To assess dose rate effect on cataractogenesis in allogeneic or autologous bone marrow transplanted patients conditioned with fractionated total-body irradiation (FTBI).

MATERIALS AND METHODS:

Between 1987 and 2001, a total of 105 patients have received TBI conditioning for Bone Marrow Transplantation (BMT) for hematological malignancies at Gulhane Military Medical School. 12 Gy FTBI was applied in 6 fractions over 3 consecutive days with a Co60 teletherapy machine. 46 patients who have survived and were followed up after more than one year were evaluated for cataractogenesis in relation to dose rate. Conditioning therapy included only cyclophosphamide (60 mg/kg/day for two days) + TBI with no steroid and veno-occlusive disease prophylaxis.

RESULTS:

The median follow-up is 32 months. Posterior subcapsular cataract developed in 5 eyes of three patients out of 46 patients. The 5-year and 10-year estimated cataract incidence in the high-dose rate (> 0.04 Gy/min) group was 29% and 43% respectively while no cataracts occurred in the low-dose rate (< or = 0.04 Gy/min) group. Cataract development in the high-dose rate group versus low-dose rate group was statistically significant (p < 0.039).

CONCLUSION:

Cataract is a late side effect of TBI. Low-dose rate fractionated TBI is a reliable conditioning program in BMT with effective lens sparing to avoid cataractogenesis.

OBJECTIVES:

One of the major challenges in the post-transplant period is nutrition. In this prospective, non-randomized study, total parenteral nutrition (TPN) was given to 31 patients and partial parenteral nutrition (PPN) was given to 30 patients undergoing autologous hematopoietic stem cell transplantation for solid tumors or hematologic malignancies to compare the effects of these parenteral nutrition modalities on post-transplant hematological engraftment, blood chemistry, and supportive therapy requirements.

METHODS:

All patients in the TPN group and 17 patients in the PPN group received growth factor in the post-transplant period. Both groups did not differ with respect to sex, age, and reinfused CD34(+) cell numbers.

RESULTS:

After transplantation body mass index and body weight decreased significantly in both groups (P < 0.001). Whereas serum albumin concentrations did not decrease significantly in the TPN group, it fell markedly in the PPN group at the end of parenteral nutrition (P = 0.019). After parenteral nutrition, blood chemistry was also remarkable for serum urea and glucose levels, which were elevated significantly in the TPN group (P < 0.001 and P = 0.03, respectively). Patients receiving TPN had a higher incidence of positive microbial cultures and clinical infection than did patients receiving PPN (64.5% versus 40%, P = 0.05). The most striking result was a delay in platelet engraftment for the TPN group compared with the PPN group (15.54 and 12.93 d, respectively; P = 0.014). This difference was also noted in patients using growth factor in the PPN group (P = 0.017). Parallel to these results, platelet transfusion requirement increased in the TPN group compared with the PPN group (1.93 versus 1.16 U, P = 0.004). Both groups were unremarkable for leukocyte recovery and red blood cell transfusion requirement.

CONCLUSIONS:

Consequently, TPN has some pitfalls of hyperglycemia, infection tendency, delayed platelet engraftment, and increased platelet transfusion requirement. Therefore, it should not be used as a standard nutrition support for patients undergoing autotransplantation.

AIMS AND BACKGROUND:

Leptin is a protein that affects the metabolic, neuroendocrine, reproductive and hematopoietic systems and is involved in the regulation of body weight. The possible role of leptin in cancer patients, whose aforementioned systems show disorders at various levels, has been investigated by only a few studies and the results are quite contradictory.

METHODS:

In this study serum leptin levels were investigated in 36 patients with colon cancer having no weight loss or anorexia and in 36 healthy volunteers. Serum leptin levels were measured by radioimmunoassay.

RESULTS:

Significantly positive correlations were found between serum leptin level and/or body mass index (BMI) in patient and control groups (r = 0.842, P < 0.001 and r = 0.785, P < 0.001; r = 0.880, P < 0.001 and r = 0.523, P = 0.001). Serum leptin levels of colon cancer patients were significantly lower than those of the control group (8.79 vs 15.95 ng/mL, P = 0.003). BMI and age of the colon cancer patients were not different from those of the control group. Serum leptin levels of early-stage patients (n = 15) did not differ from those of advanced-stage patients (n = 21) (7.74 vs 9.54 ng/mL, P = 0.542), nor was there any difference in the serum leptin levels of patients who did and patients who did not receive chemotherapy. There was no correlation in cancer patients between serum leptin levels and CEA or CA19-9 (r = 0.015, P = 0.929 and r = 0.097, P = 0.574).

CONCLUSION:

Low serum leptin levels found in colon cancer patients without weight loss suggest that another mechanism regulating the leptin levels might be responsible.

OBJECTIVE AND IMPORTANCE:

An unusual, but not unique, case of cerebellar aspergillosis associated with autologous peripheral blood stem cell transplantation for breast cancer is presented.

CLINICAL PRESENTATION:

A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections.

INTERVENTION:

After removal of pus and the abscess wall, the patient received local application of amphotericin B (AmB). She received AmB 1 mg/kg/d for 3 months and itraconazole 100 mg/kg/d for 1 year. After 3 months of AmB treatment, magnetic resonance imaging revealed that disease had not recurred.

CONCLUSION:

In cases of central nervous system aspergillosis, to increase the therapeutic efficiency, AmB can also be applied to the abscess cavity. Computed tomographic and contrast-enhanced magnetic resonance imaging scans play an important role in establishing early diagnosis in high-risk, immunocompromised patients.

The high incidence and the severe symptoms of cancer have a considerable effect on quality of life in patients. The relationship between quality of life in patients with cancer and treatment, early diagnosis, disease acceptance, pain, psychological distress, loss of organ, duration of disease, and caregivers was investigated. This study included 508 patients with cancer treated in either inpatient or outpatient clinics of 5 oncology centers in Ankara, Turkey, between August 1 998 and January 2000. Patients were selected by interviews. Data were collected by a questionnaire to determine disease features and to evaluate patients’ quality of life. We found that several disease features, including treatment, early diagnosis, disease acceptance, pain, psychological distress, and caregivers, had an effect on patients’ quality of life (P < 0.05), whereas loss of organ and duration of disease did not. The results of this study underline the significant effect of psychosocial care programs on quality of life. In the future, assessments of quality of life can help healthcare personnel to prepare psychosocial care programs.

BACKGROUND:

Leptin is a peptide hormone that has a role in the regulation of body weight and has effects on metabolic, neuroendocrine, reproductive and hematopoietic systems. Breast cancer has also been associated with obesity and reproductive hormones, especially estradiol. Only a few studies have investigated the relation between plasma leptin and risk of breast cancer and only one study evaluated the effect of tamoxifen on leptin levels in patients with breast cancer.

METHODS:

We investigated serum leptin levels in gender-, body mass index (BMI)- and age-matched breast cancer patients and healthy individuals (58 of each).

RESULTS:

Serum leptin levels were measured by radioimmunoassay (Human Leptin RIA Kit). Serum leptin levels in the breast cancer patients were significantly higher than those in the control group (27.00 versus 17.65 ng/ml, p = 0.019). There were no differences with respect to BMI and age between control and breast cancer patients. There were no significant differences in BMI and leptin levels between pre- and postmenopausal patients (27.00 +/- 1.39 and 27.19 +/- 0.81 kg/m(2), 26.81 +/- 6.25 and 27.06 +/- 2.98 ng/ml) (p > 0.05). We found no difference in serum leptin level between early and late stages of patients (22.38 versus 31.30 ng/ml, p = 0.086). However, the serum leptin level in patients using tamoxifen was significantly higher than that of patients not using tamoxifen (32.71 and 19.39 ng/ml, respectively p = 0.009). There was no correlation between CA 15-3 and leptin level (r = 0.069, p = 0.610).

CONCLUSION:

High serum leptin levels seen in breast cancer patients are not related to stage of the disease or to cancer itself but may be associated with the use of tamoxifen.

Primary non-Hodgkin’s lymphoma of the liver is very uncommon, and fewer than 100 cases have been reported in the literature. Most reports describe either solitary or multiple mass lesions in the liver. A diffuse lesion without nodule formation is a relatively rare form of the disease. The histologic feature of the disease is a predominantly large cell lymphoma of B-cell lineage. We report a case of primary B-cell non-Hodgkin’s lymphoma which had diffusely infiltrated the liver without nodule formation.

BACKGROUND:

The reported incidence of cancer during pregnancy is between 0.07% and 0.1%. The incidence of colorectal carcinoma in pregnancy was 1 per 13,000 liveborn deliveries during 1981-1989.

CASE:

A 33-year-old woman, gravida 2, para 1, was admitted at 30 weeks’ gestational age with a history of rectal bleeding and right upper quadrant pain. Abdominal ultrasound and magnetic resonance imaging revealed a mass located on the posterior part of the right liver and a fetus with vertex presentation. Primary cesarean section and a right hemicolectomy and wedge biopsy from the metastatic lesion on the right side of the liver at 34 weeks’ gestation was performed. Histologic examination confirmed serosal and lymph node invasion of moderately differentiated mucous-secreting adenocarcinoma of the cecum and adenocarcinoma metastatic to the liver. The patient received systemic chemotherapy.

CONCLUSION:

Only 1 of 41 cases of colon cancer during pregnancy above the peritoneal reflection has been reported to be localized to the cecum. Our case is the second such one. Women with colorectal carcinoma during pregnancy usually have a poor prognosis, which may be attributable to younger age and delay in diagnosis since the initial symptoms often are presumed attributed to normal pregnancy, as in this case.

Plasma and erythrocyte lipid peroxidation levels of 20 patients with histopathologically confirmed testis cancer and 20 healthy control individuals were studied between November 1995 and June 1997. The group with testis cancer had a mean age of 24.8+/-8.2 yr and the control group’s mean age was 28.3+/-6.9 yr. Stage distribution of the testis cancer cases were 4 of stage A, 10 of stage B, and 6 of stage C. Blood samples of the patients were drawn after orchiectomy and after 12 h fasting before chemotherapy. Mean plasma and erythrocyte lipid peroxidation levels were detected to be 14.51+/-5.30 nmol malondialdehide (MDA)/mL and 9.30+/-2.06 nmol MDA/g hemoglobin (Hb), respectively, in the testis cancer group, whereas the healthy control group had mean plasma and erythrocyte lipid peroxidation levels of 10.7+/-1.82 nmol MDA/mL and 6.18+/-1.68 nmol MDA/g Hb, respectively. Plasma and erythrocyte lipid peroxidation values of the testis cancer patients were determined to be statistically significantly higher than that of the health control group (p < 0.001, p < 0.001). No significant correlation was determined between plasma, erythrocyte lipid peroxidation levels and tumor markers. In conclusion, it can be said that an increase in the lipid peroxidation may play a role in the pathogenesis of testis carcinomas in addition to the other causes.

With modern treatment modalities it is possible to obtain a long survival in patients with non-seminomatous testicular cancer. Chemotherapy is the mainstay of treatment in metastatic cases. High-dose chemotherapy and autologous peripheral blood stem cell transplantation is a good salvage treatment for recurrent cases. However, the modality has serious complications. We present a rare case of recurrent spontaneous pneumothorax due to rupture of residual cystic lesions after high-dose chemotherapy in a patient with pulmonary metastases. Such a situation has been rarely reported.

The Turkish Apheresis Group has maintained a national registry for apheresis activities since 1997. The hemapheresis practice of Turkey in 1998 is summarized in brief detail in this article. A total of 30, 136 apheresis procedures were performed at 31 different apheresis centers. At 10 centers, 145 peripheral blood stem cell (PBSC) apheresis were performed on 82 patients in allogeneic setting and at 17 centers, 981 PBSC apheresis were performed on 271 patients in autologous setting. Frequently observed adverse effects during PBSC apheresis were mild tremor and chills, paresthesia and nausea in 15% of the patients and donors. Vascular access complications, particularly observed in autologous setting due to central venous catheters were encountered in 10% of the procedures. Eight hundred and sixty-nine therapeutic plasma exchange procedures were performed at 21 centers on 172 patients, most commonly for neurological disorders and thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Therapeutic cytapheresis procedures like leukapheresis, plateletapheresis and erythrocyte apheresis were performed especially for cytoreduction in myeloproliferative disorders. A total of 204 cytapheresis procedures (66% leukapheresis, 33% plateletapheresis and 1% erythrocytapheresis) were performed on 134 patients in 15 centers. Donor plateletapheresis was the most used apheresis procedure, reaching a total of 28.016 in 1998. Many university hospitals and a few state hospitals are performing above-mentioned apheresis procedures with great success and acceptable side effects. According to these data we are planning prospective trials and will establish National Standards of Practice.

Male breast cancer, consisting only 1% of all breast cancers, is occasionally associated with other primary malignancies, especially in patients with familial breast cancer history. Sporadic male breast cancers with another primary tumor are extremely rare. We report a 67-year-old male with asynchronous bilateral breast cancer and prostate cancer without familial breast cancer history.

BACKGROUND:

There is a tendency to use only one apheresis collection to reduce the morbidity and the cost of peripheral blood stem cell collection. We studied whether rapid and complete engraftment could be achieved by single apheresis by using only Filgrastim without large volume apheresis in previously treated patients.

METHODS:

Engraftment of single apheresis in 25 patients was compared with those of multiple apheresis in 26 patients; 52% of patients in the single apheresis group and 62% of patients in the multiple apheresis group were heavily pretreated. All patients received 10-15 microg/kg/day of Filgrastim starting on day 14 after 3-4 cycles of induction chemotherapy. Apheresis was performed using Cobe Spectra on day 4, 5 or 6 in the single apheresis group and every other day in the multiple apheresis group after day 3.

RESULTS:

The median collection volume was 250 ml (250-300 ml) in the single apheresis group and 750 ml (200-1500 ml) in the multiple apheresis group. The median CD34(+) cell number was not significantly different in the two groups (11.79 vs. 9.38×10(6)/kg). The median times to achieve leukocytes > or =1×10(9)/l and platelets > or =50×10(9)/l counts were 10 days (8-21 days) and 15 days (9-38 days) in the single apheresis group vs 11 days (8-23 days) and 20 days (10-32 days) in the multiple apheresis group, respectively (p<0.05). Antibiotic use was less in the single apheresis group than the multiple apheresis group (9 vs. 12 days, p<0.05).

CONCLUSION:

Adequate numbers of peripheral stem cells were harvested by G-CSF in a single apheresis without large volume apheresis even in heavily pretreated patients. Rapid and complete engraftment occurred in all patients and it was faster in single than multiple apheresis.

Serum copper, zinc levels, and the Cu/Zn ratio were evaluated in 31 patients with breast cancer and 35 healthy controls. Copper and zinc were determined by atomic absorbtion spectrophotometry. The mean serum copper level and the mean Cu/Zn ratio in patients with breast cancer were significantly higher than the control group (p < 0.001 and p < 0.001). In addition, the mean serum zinc level in patients with breast cancer was significantly lower than the control group (p < 0.001). Neither serum copper and zinc levels nor the Cu/Zn ratio were of value in discriminating of the disease activity and severity. Interestingly, the Cu/Zn ratio in premenopausal patients was higher than postmenopausal patients (p < 0.05) and this was not related to age. The further combined biological and epidemiological studies are necessary to investigate the roles of copper and zinc in breast cancer.