Taner Demirer

Diet and stomach cancer incidence : a case-control study in Turkey

A case‐control study of diet and stomach cancer was conducted in Ankara, Turkey, between December 1987 and March 1988. One hundred patients with adenocarcinoma of the stomach were matched with 100 control subjects according to age, sex, and residential area. A dietary questionnaire was administered to all subjects by one of the authors. Gastric cancer patients consumed less fresh fruit and yellow‐green vegetables (P < 0.0001) and meats (P < 0.001), and more salted food (P < 0.001), condiments (P < 0.0001), and salt (P < 0.001) compared with the control group. Twenty‐four percent of the gastric cancer patients and 4% of the controls had no refrigerator (P < 0.0001). There was no difference between the two groups with regard to the consumption of starches, fried foods, cereals, milk, dairy products, tea, alcohol, and tobacco. Stomach cancer patients brushed their teeth less frequently (P < 0.0001) and had more deficient teeth (P < 0.0001) compared with the control group.

High-Dose Chemotherapy With Autologous Stem-Cell Support As Adjuvant Therapy in Breast Cancer: Overview of 15 Randomized Trials

PURPOSE Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets. METHODS We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status. RESULTS Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients. CONCLUSION Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown.

Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors

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.

Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of different doses of rhG-CSF.

Summary. To date, no randomized study has compared different doses of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG‐CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 µg/kg/d (n = 25) of rhG‐CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 µg/kg/d of rhG‐CSF was 2·36 × 106/kg (range, 0·21–7·80), compared with 7·99 (2·76–14·89) after 16 µg/kg/d (P < 0·001). Twenty out of 25 (80%) patients in the low‐dose and 23 out of 25 (92%) in the high‐dose rhG‐CSF arm underwent high‐dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 µg/kg and 16 µg/kg of rhG‐CSF were 12 (10–20) and 9 (8–11) respectively (P < 0·001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0·10), number of red blood cell (P = 0·56) and platelet transfusions (P = 0·22), days of total parenteral nutrition requirement (P = 0·84), fever (P = 0·93) and antibiotics (P = 0·77), and number of different antibiotics used (P = 0·58). These data showed that higher doses of rhG‐CSF following submyeloablative mobilization chemotherapy were associated with a clear dose–response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 µg/kg/d was as effective as 16 µg/kg/d except for a rapid neutrophil engraftment in the high‐dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG‐CSF, lower doses may be used for PBSC collections following chemotherapy‐based mobilization regimens in this cost‐conscious era.

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

PURPOSE High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. METHODS We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. RESULTS The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. CONCLUSION Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy.

Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation.

A 46-year-old white male with small cell lung cancer (SCLC) limited to the thorax developed autoimmune thrombocytopenic purpura (AITP), following a cyclophosphamide, paclitaxel and G-CSF-containing regimen for peripheral blood stem cell (PBSC) mobilization. AITP associated with small or non-small cell lung cancer has been reported. We considered that the AITP in this case may be a part of paraneoplastic syndrome, which is frequently seen in patients with SCLC. The patient received HDC and autologous PBSC transplantation (APBSCT) for SCLC and the AITP resolved following transplantation, thus supporting the concept of HDC + APBSCT for the treatment of autoimmune diseases.

Recombinant human granulocyte colony-stimulating factor (rh-G-CSF) may accelerate hematopoietic recovery after HLA-identical sibling allogeneic peripheral blood stem cell transplantation.

We studied the effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation. Fifty-six patients with hematological malignancies who underwent allogeneic PBSC transplantation between 1995 and 1998 were entered into this study. Twenty-eight patients who received daily G-CSF from day +1 after allogeneic PBSC transplantation until the absolute neutrophil count (ANC) reached >0.5 × 109/l for 3 consecutive days were compared with 28 patients (control group) who did not receive G-CSF in a non-randomized manner. The study group and the control group were comparable with respect to baseline patient and transplantation characteristics. Median times to ANC of >0.5 × 109/l and 1 × 109/l with or without G-CSF were 12 days (range 8–21), 13 days (10–32) (P = 0.04) and 13 days (9–21), 15 days (11–44) (P = 0.02), respectively. Median times to reach a platelet count of >20 × 109/l with and without G-CSF were 11 days (0–20) and 13 days (9–26), respectively (P = 0.03). The incidence of febrile episodes was significantly lower with G-CSF, 75% vs 100% (P = 0.008). Patients receiving G-CSF had less grade III–IV mucositis than those who did not receive G-CSF (P = 0.01). There was also no increase in the incidence and severity of acute GVHD in patients using G-CSF (P = 0.22). Although the number of relapsing patients was greater in the G-CSF group (seven vs three patients), this was not statistically significant (P = 0.24). Disease-free and overall survival rates did not differ between the two groups (P = 0.58 and 0.53, respectively). The administration of G-CSF after allogeneic PBSC transplantation provided faster neutrophil and platelet engraftment associated with less severe mucositis and less febrile episodes. Bone Marrow Transplantation (2001) 27, 499–505.

Influence of post‐transplant recombinant human granulocyte colony‐stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation

Summary. This study evaluated of the effect of post‐transplant recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) administration on the parameters of peritransplant morbidity. Three sequential and consecutive cohorts of 20 patients each received either post‐transplant rhG‐CSF at a dose of 5 µg/kg/d i.v. in the morning, starting on d 0, d 5, or no rhG‐CSF. Patients who received rhG‐CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG‐CSF (P < 0·001 for ANC ≥ 0·5 and 1 × 109/l). RhG‐CSF administration was not significantly associated with more rapid platelet engraftment. RhG‐CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P = 0·002 and 0·001 respectively), antibiotic administration (P < 0·001 and 0·006 respectively) and shorter hospitalization (P < 0·001 and 0·001 respectively) compared with the reference group. There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity. In conclusion, rhG‐CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and non‐prophylactic antibiotic administration. This study also showed that starting rhG‐CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this cost‐conscious era.

Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF

The optimal timing for recombinant human (rh)G-CSF administration after chemotherapy for PBSC mobilization has not yet been determined. In this study, we compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late), in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC mobilization with CE (CY 4 g/m2 on day 1 and etoposide 200 mg/m2 on days 1–3). The rhG-CSF dose was 10 μg/kg/day for all patients. Both groups were comparable in terms of sex, age and number of previously given different chemotherapy regimens. Duration of neutropenia, CD34+ cell count on the first day of apheresis and numbers of aphereses were not statistically different between the two arms. However, the number of doses of rhG-CSF up to the first cycle of apheresis procedures was significantly lower in the late group than in the early group (P=0.005). The median number of total CD34+ cells collected was 10.54 × 106/kg (range 0.11–37.27) in the early group and 10.81 × 106/kg (range 0.17–49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC mobilization after late use of rhG-CSF is an effective approach and therefore, in routine clinical practice, late rhG-CSF may be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.

Acute myeloblastic leukemia associated with hyperleukocytosis and diabetes insipidus

Two cases with acute myeloblastic leukemia (AML M4-FAB) associated with diabetes insipidus (DI) are presented here. Both patients presented with hyperleucocytosis. One had a white blood cell count (WBC) of 150 x 10(9)/L and the second patient had 200 x 10(9)/L. One of these patients was a 40 year-old male and MRI of the hypophysis showed an infindibuler mass. This patient did not respond to remission induction chemotherapy and reinduction chemotherapy was given. The other patient was a 16-year-old male with a normal CT scan of the head. Both patients had DI with typical clinical and laboratory findings. The first patient died early on during reinduction chemotherapy and the second patient died of intracranial bleeding before induction chemotherapy was given. These findings are consistent with the data in the literature suggesting that the prognosis of AML associated with DI is poor and that these cases generally present with hyperleucocytosis.