Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: a study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party.

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.

Serum chitotriosidase levels in cancer patients undergoing high dose chemotherapy and stem cell transplantation.

OBJECTIVE: Human chitotriosidase (ChT) is an active chitinase expressed by activated phagocytes. Increased ChT activity has been reported in systemic Candida albicans infections and in Gram-negative and Gram-positive bacterial infections, indicating that an increase in ChT activity reflects phagocyte activation. The aim of this study was to determine the changes in serum ChT activity in patients who underwent high dose chemotherapy (HDC) and stem cell transplantation (SCT), who are at an increased risk for fungal and bacterial infections due to depression of the immune system during the neutropenic period. PATIENTS AND METHODS: A total of 55 SCT patients were included in the study. Serum ChT activity was determined before the initiation of HDC and during the neutropenic period after hematopoietic stem cell reinfusion on post-transplant first, fifth and tenth days. RESULTS: Chitotriosidase levels before transplantation were significantly lower than the results at first, fifth and tenth days post-hematopoietic stem cell reinfusion. CONCLUSIONS: Although the number of neutrophils was low, ChT enzyme activity was high in newly produced granules of neutrophils. Chitotriosidase may be supplemented as a drug for preventing and treating infections in the near future.

Turkish Transplant Registry: a comparative analysis of national activity with the EBMT European Activity Survey.

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.

Outcome of patients with stage II and III nonseminomatous germ cell tumors: results of a single center.

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.

Oxidative stress in patients undergoing high-dose chemotherapy plus peripheral blood stem cell transplantation.

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.

Evaluation of dose homogenization and radiation carcinogenesis risk in total body irradiation for bone marrow transplantation.

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.

Changes in immunological recovery in patients who received post-transplant G-CSF or GM-CSF after autologous peripheral blood stem cell transplantation (PBSCT).

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.

Effects of tamoxifen on the serum leptin level in patients with breast cancer.

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.

Colon cancer during pregnancy. A case report.

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.

The relationship between disease features and quality of life in patients with cancer--I.

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.

Plasma and erythrocyte lipid peroxidation levels in patients with testis tumor after orchiectomy.

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.

Recurrent spontaneous pneumothorax following high-dose chemotherapy in a patient with non-seminomatous testicular cancer with pulmonary metastases.

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.

National survey of hemapheresis practice in Turkey (1998).

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.

Bilateral male breast cancer and prostate cancer: a case report.

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.

A successful and simplified filgrastim primed single apheresis method without large volume apheresis for peripheral blood stem cell collection.

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. 9.38x10(6)/kg). The median times to achieve leukocytes > or =1x10(9)/l and platelets > or =50x10(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.