Gülsüm Özet

Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group.

The combination of melphalan–prednisone–thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan–prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m2/d) and P (60 mg/m2/d) for 4 d every 6 wk (n = 62) or MP and thalidomide (100 mg/d) continuously (n = 60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease‐free (DFS) and overall survival (OS). Overall, MPT‐treated patients were younger (median 69 yr vs. 72 yr; P = 0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow‐up (median OS 26.0 vs. 28.0 months, P = 0.655; DFS 21.0 vs. 14.0 months, P = 0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3–4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P = 0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n = 8, 14.0%) than in the MPT arm (n = 2, 3.4%; P = 0.053). Long‐term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P = 0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation. This study is registered at http://www.clinicaltrials.gov as #NCT00934154.

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.

Coagulopathy parameters in patients with Crimean‐Congo hemorrhagic fever and its relation with mortality

Background: Crimean‐Congo hemorrhagic fever (CCHF) is an acute illness affecting multiple organ systems and characterized by ecchymosis, visceral bleeding, and hepatic dysfunction. In this study, we aimed to investigate the profile of coagulopathy markers (platelet count, activated partial tromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen, protein C, protein S, antithrombin III, activated protein C resistance (APCR), and D‐dimer) and their clinical significance in 83 CCHF‐infected patients. Subjects and methods: We studied 83 CCHF patients who were admitted to Ankara Numune Education and Research Hospital during the spring and summer of2007. We compared the coagulopathy markers of fatal CCHF patients (n=9) with nonfatal cases (n=74). Results: Platelet count, PT, aPTT, INR, and fibrinogen were prognostic factors associated with mortality for CCHF. Especially, platelet count<20×109 cells/l and aPTT>60 sec were important. Protein C, protein S, APCR, and antithrombin III levels were not associated with mortality. Conclusion: Laboratory tests including classical parameters (platelet count, PT, aPTT, INR, and fibrinogen) of coagulopathy seem to be enough for the followup of CCHF. Protein S, protein C, APCR, and D‐dimer levels were not associated with mortality. J. Clin. Lab. Anal. 24:163–166, 2010.

Analysis of lymphocyte subgroups in Crimean-Congo hemorrhagic fever

OBJECTIVES This study examined the association between lymphocyte subgroups and mortality in patients with Crimean-Congo hemorrhagic fever (CCHF) in Turkey. METHODS During the spring and summer of 2007, peripheral blood was collected from hospitalized patients with suspected CCHF. Lymphocyte subgroups were characterized by fluorescence-activated cell sorting. CCHF cases were confirmed by detecting viral RNA by PCR and/or IgM antibodies by ELISA. Lymphocyte subgroups were compared between fatal and non-fatal cases. The correlation between lymphocyte subgroups and viral loads was also investigated. RESULTS Seventy-seven confirmed cases of CCHF were included in this study (five cases were fatal (6.5 %)). No differences in lymphocyte subgroups were found between fatal and non-fatal cases, except for significantly higher CD3+CD8+ T cells in the fatal cases (p=0.017). A positive correlation between viral load and CD3+CD8+ T cells was also detected (p=0.044). There was no correlation between other lymphocyte subgroups and viral load. CONCLUSIONS Higher levels of CD3+CD8+ T lymphocytes were detected in fatal compared to non-fatal CCHF cases. Despite this cytotoxic immune activation, a fatal outcome could not be prevented. We hypothesize that high viral load and other factors may influence this outcome, although more studies are required to explain the pathogenesis of CCHF.

An unusual case of spontaneous acute tumor lysis syndrome associated with acute lymphoblastic leukemia: a case report and review of the literature.

Department of Hematology, Karaelmas University Medical School, Zonguldak, Turkey, Department of Cardiology, Karaelmas University Medical School, Zonguldak, Turkey, Department of Medical Oncology, Karaelmas University Medical School, Zonguldak, Turkey, Department of Hematology, Ankara Numune Education and Research Hospital, Ankara, Turkey, and Department of Immunology, Karaelmas University Medical School, Zonguldak, Turkey

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.

Risk factors for thrombophilia in young adults presenting with thrombosis

The increased risk for thrombosis is known as hypercoagulability or thrombophilia. Here, we investigated risk factors for thrombophilia which were screened in young adult patients presenting with thrombotic events or with recurrent abortions with unknown etiology. A total of 115 patients aged between 16 and 50 years who were found to harbor thrombophilia were retrospectively evaluated. The laboratory investigations performed for the assessment of thrombophilia included protein C, protein S, antithrombin III deficiencies, activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylenetetrahydrofolate reductase (MTHFR) gene mutations, factor VIII elevation, lupus anticoagulant and antiphospholipid antibodies (APA). In 66% of the cases a single thrombophilic defect was identified while some of the patients had combined thrombophilic defects. The most common thrombophilic defect was mutation in the MTHFR gene, and was followed by FVL mutation, the presence of APA and PT 20210 gene mutation, respectively. The patients were divided into two different age groups, 16–35 and 36–50 years, and arterial thrombosis was more common in the older age group. Our results indicated that some important thrombophilic defects such as gene mutations may appear in young adult patients presenting with thrombotic events.

Isolated central nervous system relapse during cytologic and molecular hematologic remission in two patients with acute promyelocytic leukemia.

Abstract Extramedullary involvement in the absence of bone marrow disease is rare in patients with acute promyelocytic leukemia (APL). We report two patients with APL who had central nervous system (CNS) relapse without evidence of cytologic and molecular disease of bone marrow after all-trans-retinoic acid (ATRA) treatment. Both of the patients were treated successfully with combination of intrathecal chemotherapy and radiotherapy with or without systemic chemotherapy. Although increasing number of cases with extramedullary involvement of APL after ATRA including therapy have been reported, further studies with a large series of patients are necessary to determine whether ATRA increases the risk of development of extramedullary involvement of disease in patients with APL.

Tekrarlayan düşük yapan kadınlarda trombofilik risk faktörleri

Objectives: The aim of this study was to determine the thrombophilic risk factors and their frequency among women with history of recurrent abortion and a detected thrombophilic defect. Materials and methods: In this study, 41 women with history of recurrent abortion, who have one or more detected thrombophilic defects including protein S, protein C, antithrombin deficiency, activated protein C resistance (APC-R), factor V Leiden (FVL), prothrombin G 20210A (PTG), methylenetetrahydrofolate reductase (MTHFR) C677 T gene mutation, antiphospholipid antibodies and elevated levels of factor VIII were retrospectively investigated. Results: The most common detected thrombophilia defect (53.7%) was MTHFR gene mutation. While 22 of 41 patients (53.7%) had more than one concomitant defect, 20 of them had two concomitant defects and the remaining had three defects. Conclusion: MTHFR gene mutation, alone and/or with, concurrent thrombophilic defects was the most frequent factor for hereditary thrombophilia among our patients with a history of recurrent abortion. J Clin Exp Invest 2010; 1(3): 168-172

Unusual extramedullary hematopoiesis in a patient receiving granulocyte colony-stimulating factor.

A 42-year-old woman was diagnosed with myelodysplastic syndrome with fibrosis that developed bilaterally, cervical lymphadenopathy and cutaneous infiltration by trilineage extramedullary hematopoiesis after granulocyte colony-stimulating factor therapy because of severe neutropenia. Hepatosplenomegaly was not observed during her follow-up. Extramedullary hematopoiesis disappeared after growth factor therapy was stopped. Although the neutropenia was alleviated by growth factor administration, the appearance of an unusual involvement of extramedullary hematopoiesis should be kept in mind.