Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

Central nervous system neurotoxicity associated with nelarabine in T-cell acute lymphoblastic leukemia.

INTRODUCTION: Nelarabine, a prodrug of arabinosylguanine has lineage-specific toxicity for T lymphoblasts and is used to treat refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma patients. The most commonly observed adverse effects associated with nelarabine are mainly hematological, i.e. neutropenia, anemia, and thrombocytopenia. Additionally, neurological, and gastrointestinal toxicities have been reported. Central nervous system neurotoxicity associated with nelarabine is very rare. CASE DESCRIPTION: A 37-year-old man patient diagnosed with T-cell acute lymphoblastic leukemia had experienced generalized tonic-clonic seizure which lasted for a few seconds and upper extremity weakness after three weeks of the nelarabine infusion. Computed tomography and magnetic resonance imaging have shown periventricular and nucleus caudatus abnormalities. Radiological findings suggested toxic leukoencephalopathy and acute infarct of right nucleus caudatus. MANAGEMENT AND OUTCOME: After high-dose steroids, intravenous immunoglobulin, and support treatment, his neurologic symptoms disappeared except for mild peroral numbness. However, radiological sequelae persisted despite clinical improvement. CONCLUSION: Physicians involved in the care of these patients who use nelarabine should be aware of the fact that cerebral toxicity of the nelarabine may occur especially in the presence of predisposing factors. It is crucial to monitor closely those patients receiving nelarabine and also those who have additional predisposing factors for neurotoxicity.

Increased Circulating Copeptin Levels Are Associated with Vaso-Occlusive Crisis and Right Ventricular Dysfunction in Sickle Cell Anemia.

OBJECTIVE: Vaso-occlusive crisis (VOC) is a common clinical manifestation of sickle cell anemia (SCA) and is associated with increased proinflammatory mediators. Copeptin is the C-terminal part of the prohormone for provasopressin and seems clinically relevant in various clinical conditions. Right ventricular (RV) dysfunction significantly appears in SCA patients due to pulmonary hypertension. This study aimed to investigate the association of copeptin levels in VOC patients and evaluate RV dysfunction. MATERIALS AND METHODS: A total of 108 patients were enrolled in the study. Twenty-eight SCA patients in steady state (30.2 ± 0.9 years), 25 SCA patients in VOC (36.8 ± 11.8 years), and 55 healthy individuals (31.9 ± 9.4 years) with HbAA genotype were included. Clinical, echocardiographic, and laboratory data were recorded. ELISA was used for the determination of serum levels of copeptin. RESULTS: VOC patients had significantly higher copeptin level compared both with controls and SCA subjects in steady state (22.6 ± 13.0 vs. 11.3 ± 5.7 pmol/L, 22.6 ± 13.0 vs. 12.4 ± 5.8 pmol/L, p = 0.009 for both). Additionally, the copeptin level was significantly higher in SCA patients with RV dysfunction than those without RV dysfunction (23.2 ± 12.2 vs. 15.3 ± 9.5 pmol/L, p = 0.024). Multiple logistic regression analysis revealed that high-sensitivity C-reactive protein and copeptin levels were found to be associated with VOC. CONCLUSION: This study showed that copeptin and hs-CRP levels were increased in patients with VOC, and it was found that RV dysfunction was more common in SCA patients with VOC than in the control group. Copeptin can be considered for use as a potential biomarker in predicting VOC crisis in SCA patients and in the early detection of patients with SCA who have the potential to develop RV dysfunction.

East Mediterranean region sickle cell disease mortality trial: retrospective multicenter cohort analysis of 735 patients.

Sickle cell disease (SCD), one of the most common genetic disorders worldwide, is characterized by hemolytic anemia and tissue damage from the rigid red blood cells. Although hydroxyurea and transfusion therapy are administered to treat the accompanying tissue injury, whether either one prolongs the lifespan of patients with SCD is unknown. SCD-related mortality data are available, but there are few studies on mortality-related factors based on evaluations of surviving patients. In addition, ethnic variability in patient registries has complicated detailed analyses. The aim of this study was to investigate mortality and mortality-related factors among an ethnically homogeneous population of patients with SCD. The 735 patients (102 children and 633 adults) included in this retrospective cohort study were of Eti-Turk origin and selected from 1367 patients seen at 5 regional hospitals. A central population management system was used to control for records of patient mortality. Data reliability was checked by a data supervision group. Mortality-related factors and predictors were identified in univariate and multivariate analyses using a Cox regression model with stepwise forward selection. The study group included patients with homozygous hemoglobin S (Hgb S) disease (67 %), Hb S-ß(0) thalassemia (17 %), Hgb S-ß(+) thalassemia (15 %), and Hb S-α thalassemia (1 %). They were followed for a median of 66 ± 44 (3-148) months. Overall mortality at 5 years was 6.1 %. Of the 45 patients who died, 44 (6 %) were adults and 1 (0.1 %) was a child. The mean age at death was 34.1 ± 10 (18-54) years for males, 40.1 ± 15 (17-64) years for females, and 36.6 ± 13 (17-64) years overall. Hydroxyurea was found to have a notable positive effect on mortality (p = 0.009). Mortality was also significantly related to hypertension and renal damage in a univariate analysis (p = 0.015 and p = 0.000, respectively). Acute chest syndrome, splenic sequestration, and prolonged painful-crisis-related multiorgan failure were the most common causes of mortality. In a multivariate analysis of laboratory values, only an elevated white blood cell count was related to mortality (p = 0.009). These data show that despite recent progress in the treatment of SCD, disease-related factors continue to result in mortality in young adult patients. Our results highlight the importance of evaluating curative treatment options for patients who have an appropriate stem cell donor in addition to improving patient care and patient education.

Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy.

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population.

Late onset epstein barr virus seropositive posttransplant lymphoproliferative disorder in two renal transplant receivers.

UNLABELLED: Posttransplant malignancy is one of the most important complications of organ transplantation. Immunosuppressive drugs, viral infections such as human herpes virus 8 or Epstein-Barr virus, exposure to carcinogenic factors such as sun, and host factors can be etiologic factors in the development of malignant disease. In this paper we report 2 cases of late posttransplant lymphoproliferative disorder with malign behavior. CONFLICT OF INTEREST: None declared.

Arterial stiffness and pulse wave reflection in young adult heterozygous sickle cell carriers.

OBJECTIVE: Pulse wave velocity (PWV) and aortic augmentation index (AI) are indicators of arterial stiffness. Pulse wave reflection and arterial stiffness are related to cardiovascular events and sickle cell disease. However, the effect of these parameters on the heterozygous sickle cell trait (HbAS) is unknown. The aim of this study is to evaluate the arterial stiffness and wave reflection in young adult heterozygous sickle cell carriers. MATERIALS AND METHODS: We enrolled 40 volunteers (20 HbAS cases, 20 hemoglobin AA [HbAA] cases) aged between 18 and 40 years. AI and PWV values were measured by arteriography. RESULTS: Aortic blood pressure, aortic AI, and brachial AI values were significantly higher in HbAS cases compared to the control group (HbAA) (p=0.033, 0.011, and 0.011, respectively). A statistically significant positive correlation was found between aortic pulse wave velocity and mean arterial pressure, age, aortic AI, brachial AI, weight, and low-density lipoprotein levels (p=0.000, 0.017, 0.000, 0.000, 0.034, and 0.05, respectively) in the whole study population. Aortic AI and age were also significantly correlated (p=0.026). In addition, a positive correlation between aortic PWV and systolic blood pressure and a positive correlation between aortic AI and mean arterial pressure (p=0.027 and 0.009, respectively) were found in HbAS individuals. Our study reveals that mean arterial pressure and heart rate are independent determinants for the aortic AI. Mean arterial pressure and age are independent determinants for aortic PWV. CONCLUSION: Arterial stiffness measurement is an easy, cheap, and reliable method in the early diagnosis of cardiovascular disease in heterozygous sickle cell carriers. These results may depend on the amount of hemoglobin S in red blood cells. Further studies are required to investigate the blood pressure changes and its effects on arterial stiffness in order to explain the vascular aging mechanism in the HbAS trait population. CONFLICT OF INTEREST: None declared.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients.

OBJECTIVE: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. MATERIALS AND METHODS: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. RESULTS: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. CONCLUSION: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. CONFLICT OF INTEREST: None declared.

HbA1c level decreases in iron deficiency anemia.

BACKGROUND: Hemoglobin A1c (HbA1c) is the major form of glycosylated hemoglobin. There are conflicting data on changes in HbA1c levels in patients with iron deficiency anemia (IDA). The present study aimed to investigate the effects of HbA1c levels in the presence of IDA, the effects of iron treatment on HbA1c levels, as well as the relationship between the severity of anemia and HbA1c levels in patients without diabetes. DESIGN AND METHODS: A total of 263 patients without diabetes mellitus (DM) who were admitted to Cukurova University, Faculty of Medicine, Department of Endocrinology and Hematology or who were followed up in this clinic and diagnosed as having IDA were included in the study. A total of 131 patients had IDA. The control group comprised 132 age-matched and sex-matched healthy individuals. RESULTS: The mean HbA1c level was significantly lower in the group with IDA (5.4%) than in the healthy control group (5.9%; p < 0.05). When the patients were divided into three groups according to the severity of anemia through Hb levels, HbA1c levels were observed to decrease as the severity of the anemia increased (5.5%, 5.4%, and 5%, respectively; p > 0.05). The HbA1c levels of the patients with IDA were higher after iron therapy (from 5.4 ± 0.5 to 5.5 ± 0.3; p = 0.057). The mean hemoglobin (Hb), hematocrit (Hct), mean cell volume (MCV), mean corpusculer hemoglobin (MCH), and ferritin values also increased after iron therapy (p < 0.05). CONCLUSION: The study results showed that IDA was associated with low HbA1c levels, and increased after iron therapy. Based on the study findings, it is necessary to consider the possible effects of IDA on HbA1c levels.

Podocyte Injury in Cases with Newly Diagnosed Multiple Myeloma.

Renal impairment is a frequent complication of multiple myeloma (MM). Our aim was to assess the expression of podocyte-associated nephrin, podocin, and vascular endothelial growth factor (VEGF) A and their relation to renal function, proteinuria, and clinical outcome in patients with newly diagnosed multiple myeloma. This study included 27 patients with newly diagnosed MM and 20 healthy volunteers as control. Patients were evaluated for clinical and laboratory parameters, renal function, proteinuria, and podocyturia at the time of diagnosis and at six months. Seven patients died before completing of treatment (within the first 6 months). Proteinuria was measured in daily urine samples. First-morning spot urine RNA was isolated, cDNA was produced, and polymerase chain reaction (PCR) was processed. Podocytes were identified by PCR tagging nephrin, podocin, and VEGF-A. The mean ages were 59.63 ± 10.21 and 34.75 ± 12.07 for patients and controls, respectively. After six months proteinuria decreased from 885.45 ± 2033.12 mg/day to 398.55 ± 811.34 mg/day (P = 0.002). Comparing to baseline urinary nephrin/creatinine, podocin/creatinine, VEGF-A/creatinine were significantly increased (P = 0.039, P = 0.001, P = 0.001 respectively) while renal function and proteinuria were improved in patients. In controls urinary protein and nephrin/creatinine were lower than that of patients (P = 0.001, P = 0.044). The presence of renal failure at the initial diagnosis was the most important for death (P <0.029). Proteinuria and renal dysfunction were found in 74% and 33%, in patients with newly diagnosed MM, respectively. The presence of podocyte injury at the beginning and also increase after therapy while improvement of proteinuria and renal failure, suggests that podocyte injury can be seen in MM and is affected with treatment. This is the first report about podocyte injury in MM.

IPS-3 Validation in 1012 cases with classical hodgkin lymphoma.

The aim of this study is to validate the IPS-3 scoring system as a prognostic indicator in 1012 patients with advanced stage classical Hodgkin Lymphoma (cHL) treated by doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). According to the IPS-3 scoring system only 3.5 % had high risk and 50.8 % had low risk disease disease and 45.8 % of the cases had intermediate risk disease. Each factors of IPS-7 and IPS-3 scoring systems (age, sex, stage hemoglobin, albumin, lymphocyte count and white cell count) were found to be significant for overall survival (OS) and progression free survival (PFS) according to univariate analyses. Two different multivariate Cox analyses were performed for OS and PFS including the IPS-3/ IPS-7 scoring system parameters. Among 7 risk factors of IPS scoring system, gender and albumin were not found as independent risk factors for both OS and PFS according to cox regression model. But all parameters such as age, stage and hemoglobin those included in IPS-3, were found to be independent significant risk factors for both models obtained for OS and PFS. The results of the study shows that the IPS-3 scoring system can be used as a prognostic indicator in ABVD treated patients in every day practice which is more easily calculate according to the IPS-7.

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.

INTRODUCTION: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. MATERIAL AND METHODS: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. RESULTS: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). CONCLUSIONS: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Efficacy of tramadol vs meperidine in vasoocclusive sickle cell crisis.

Despite progress in management, patients with sickle cell disease who are experiencing acute painful episode are often incompletely treated. We compared meperidine and tramadol with respect to their effects on the hemodynamics and pain relief in patients with sickle cell disease who were admitted to the emergency department with painful crisis. A total of 68 patients with sickle cell disease were randomly assigned to receive either tramadol 1.5 mg/kg (n = 34) or meperidine 1 mg/kg (n = 34). Hemodynamic parameters were recorded at regular intervals after analgesic infusions. Pain intensity and relief were documented by visual analog and pain relief scale, respectively. Sedation level was defined according to Ramsay sedation scale. Both meperidine and tramadol administration resulted in a significant reduction in systolic and diastolic blood pressure after 2 hours (P < .05). Efficacy in pain relief between the analgesics was more rapid and better in the meperidine group, although the degree of relief were significantly improved compared to baseline levels in both groups (P < .05). Sedation was more commonly seen in the meperidine arm. None of the patients had experienced neurotoxicity. In summary, both agents had proven safe and effective for emergent use in patients with sickle cell disease. Avoiding meperidine injections as recommended with previous guidelines needs to be carefully reconsidered especially when low doses are mentioned.

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma.

BACKGROUND: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. PATIENTS AND METHODS: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. RESULTS: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. CONCLUSION: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.

Prevalence of cytogenetic abnormalities in chronic lymphocytic leukemia in the southern part of Turkey.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL.

Avascular necrosis of the femoral head as the first manifestation of acute lymphoblastic leukemia.

Avascular necrosis of bone is a well-described complication of cancer chemotherapy containing corticosteroids and has been observed in lymphomas and acute lymphoblastic leukemia (ALL). This study reports the case of a young male patient in whom avascular necrosis of right femur head was the presenting feature of acute lymphoblastic leukemia. The temporal association in this instance implicates a pathophysiologic relationship between the development of ALL and necrosis.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study.

OBJECTIVE: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. MATERIALS AND METHODS: In this retrospective multicenter study, 130 patients of ≥60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. RESULTS: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. CONCLUSION: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Telomerase activity in myelodysplastic syndromes.

Myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Telomeres are thought to be critical in maintaining normal hematopoiesis. In this study, we assessed telomere dynamics in order to obtain further insight into the pathogenesis of MDS. We studied telomerase activity (TA) in mononuclear cells from peripheral blood (PB) and bone marrow (BM) from patients with myelodysplastic syndrome (MDS; n=24), acute myeloid leukemia (AML; n=14), chronic myeloid leukemia (CML; n=12) and 11 normal controls using a polymerase chain reaction-based telomeric repeat amplification assay. Telomerase activities (mean+/-S.D.) were found as 0.199+/-0.09, 0.414+/-0.55, 0.253+/-0.26 and 0.181+/-0.05 pg/ml in PB mononuclear cells, respectively (P>0.05). Comparison of TA of BM mononuclear cells from 19 MDS patients versus 10 BM samples from normal controls revealed no significant difference (P=0.3). There was no correlation between the levels of TA and clinical and prognostic parameters of the patients with MDS, such as degree of anemia, platelet counts on presentation, gender, presence of organomegaly, bone marrow fibrosis and BM blast percentages. Patients who had higher TA had significantly inferior survival compared with patients who had lower TA (P=0.005). Consistent with previous data, our results suggest that in patients with MDS, telomerase activity might be insufficient to compensate for the telomere shortening. Furthermore, TA might be prognostically important in patients with MDS. Measurements of enzymatic activity in association with telomere length studies may help to understand the prognostic role of telomere dynamics in patients with myelodysplastic syndromes more reliably.

Liver involvement in sickle cell disease.

BACKGROUND/AIMS: Liver involvement in sickle cell disease may take place due to the primary disease itself or to secondary conditions such as iron overload, viral hepatitis and cholelithiasis. In the present study we have tried to evaluate the frequency of hepatic dysfunction and etiological factors in 48 patients with sickle cell disease. METHODS: Clinical and laboratory investigation including liver function tests, serological tests for viral hepatitis, and abdominal ultrasonography were performed in all of the patients. Additionally, liver biopsies were taken from 13 patients. RESULTS: Intrasinusoidal sickling and Kupffer cell hyperplasia were consistently seen in all of the biopsy specimens. Hepatomegaly was present in all patients, whereas liver function test abnormalities were seen in 27%. The prevalence of cholelithiasis was found as 35%. Serological tests demonstrated the presence of hepatitis B surface antigen in three, antibody to hepatitis B virus in 19 and antibody to hepatitis C virus in four of the patients. The most significant contributory finding was the presence of hemosiderosis in histological examination of liver specimens. CONCLUSION: Our data suggest that chronic liver injury in patients with sickle cell disease seems to be a multifactorial phenomenon depending mostly on overlapping factors such as iron overload and viral damage rather than primary disease itself.