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In clinical practice the role of bone marrow evaluation (BM) in the elderly, especially in patients over 75 years old who are referred as middle/advanced old, is not clear. In this study the aim was to assess the indications, results and the contribution of BM aspiration and biopsies to the clinical management and outcomes in patients over 75 years old. All ≥75 years old patients to whom BM evaluation was performed between January 2014 and December 2018 in our clinic were assessed retrospectively. The clinical properties, laboratory, peripheral blood smear and BM aspiration/biopsy results, the applied treatments and the survival outcomes were evaluated. The mean age of the 81 included patients was 80.4±4 (75-95). There was no procedure-related complication. Cytopenias were the most frequent indication. Anemia, leukopenia and thrombocytopenia were detected in 87.6%, 25.9% and 50.6% respectively. Myelodyspastic syndrome (MDS) was the most frequent diagnosis. Multiple myeloma, myeloproliferative diseases and non-Hodgkin lymphoma were the following diagnoses. Aspiration and biopsy showed high correlation. In general the median survival was 69 months in the treated patients and 35 months in non-treated patients. Two-years overall survival was 57% in the treated and 41.7% in non-treated patients. In conclusion in order to diagnose hematological and some non-hematological disorders confined to advanced age, BM evaluation may be performed safely in patients over 75 years old. The indications of BM evaluation is different than childhood and younger adulthood. Treatment of disorders that were diagnosed with this procedure provides a survival benefit. For this reason whenever indicated, in order to diagnose and improve the survival with appropriate treatment, BM evaluation may be offered to patients in this age group., Yaşlı hastalarda, özellikle de orta/ileri yaşlılık olarak tanımlanan ≥75 yaş grubunda kemik iliği değerlendirmenin klinik uygulamalardaki yeri net değildir. Bu çalışmada ≥75 yaşındaki hastalarda yapılan kemik iliği biyopsi ve aspirasyon endikasyonlarının, sonuçlarının ve yapılan kemik iliği incelemesinin klinik yaklaşıma ve sonuçlara katkısının değerlendirilmesi amaçlanmıştır. Ocak 2014- Aralık 2018 yılları arasında kliniğimizde kemik iliği incelemesi yapılan tüm ≥75 yaş hastalar retrospektif olarak değerlendirildi. Hastaların klinik özellikleri ve laboratuvar kan değerleri, periferik yayma, kemik iliği aspirasyon ve biyopsi sonuçları, aldıkları tedaviler ve sağ kalımları değerlendirildi. Çalışmaya dâhil edilen 81 hastanın ortalama yaşı 80,4±4 yıldı (75-95). İşleme bağlı komplikasyon görülmedi. Sitopeniler en sık endikasyondu. Anemi %87,6 oranında görülürken, lökopeni %25,9 ve trombositopeni %50,6 oranında görülmekteydi. En sık konulan tanı miyelodisplastik sendromdu (MDS). Yine multipl miyelom, miyeloproliferatif hastalıklar ve non-Hodgkin lenfoma MDS’yi takip ediyordu. Aspirasyon ve biyopsi yüksek oranda uyum göstermekteydiler. Genel olarak tedavi alan hastalarda ortanca sağ kalım süresi 69 ayken, almayan grupta 35 aydı. Yine 2 yıllık genel sağ kalım tedavi alan hastalarda %57 iken, almayan hastalarda %41,7 idi. Sonuç olarak ≥75 yaş hastalarda, ileri yaşa özgü hematolojik ve bazı non-hematolojik hastalıkların tanısının konulması için kemik iliği incelemesi güvenle yapılabilir. Kemik iliği incelemesinin endikasyonları çocuk ve genç erişkinlerinkinden farklıdır. Bu incelemeyle tanısı konulan hastalıklarda uygulanan tedaviler ile sağ kalım artmaktadır. Bu nedenle endikasyon varlığında, tanının konulması ve uygun tedavinin başlanması yolu ile sağ kalımı arttırmak için kemik iliği incelemesi bu yaş grubuna önerilmelidir.

In Turkish literature there are very few studies regarding multiple primary malignancies (MPM). The aim of this study was to analyze the synchronous and the metachronous malignancies that occurred with a hematologic malignancy. All the patients with a hematologic malignancy were enrolled in this cross-sectional, definitive retrospective study. Data were obtained from the medial records. Patients characteristics including demographic features, treatment protocols and overall survival (OS) were recorded. Among 663 patients with a hematologic malignancy, there were 26 patients with MPMs (3.9%). Synchronous malignancies constitute 0.9% and metachronous malignancies were present in 3%. In men diffuse large B-cell lymphoma (DLBCL) and non-small cell lung carcinoma (NSCLC) and in women breast and acute myeloid leukemia were the most common primary and secondary MPMs respectively. The mean cumulative OS of all patients with MPMs was 246.3±33.4 months and the 5 years-OS was 91.3%. In synchronous MPMs the most frequent concomitant tumors were DLBCL and NSCLC. In metachronous tumors the median time interval between first and second malignancies was 69.5 months (range: 31-312). In four patients there were three MPMs. After radiotherapy three patients developed breast, thyroid and skin cancers and in one patient who received radioiodine for the treatment of thyroid carcinoma, DLBCL had developed. The chemotherapeutic agents applied for the primary malignancies consisted of alkylating agents, antimetabolites, anthracyclines, topoisomerase II inhibitors, monoclonal antibodies and mitotic inhibitors. In 75% of the patients with DLBCL who had received R-CHOP chemotherapy regimen, NSCLC had developed during the follow-up period. In conclusion secondary malignancies with hematologic malignancies are not rare and the clinicians should keep the possibility of secondary malignancies in mind and be suspicious during diagnostic evaluations. Warning with regard to the risk of development of secondary malignancies due to the primary treatment should be given to any patient with a hematologic malignancy. [Med-Science 2020; 9(1.000): 94-9]

The present study investigated the efficacy and safety profile of daratumumab monotherapy in 42 patients with relapsed refractory multiple myeloma through a Turkish early access program. the current findings have confirmed the efficacy of daratumumab monotherapy in heavily pretreated patients with refractory multiple myeloma because of the deep and durable responses and favorable safety and tolerability profile. 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., Janssen Pharmaceutica Turkey, The present daratumumab EAP was funded by Janssen Pharmaceutica Turkey. the authors would like to thank to Professor Sule Oktay, MD, PhD, and Cagla Ayhan, MD, from KAPPA Consultancy Training Research Ltd (Istanbul, Turkey), who contributed to the manuscript writing and statistical analyses.

Background Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. Patients and Methods In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. Results The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P Conclusion The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

Background Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. Methods Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. Results A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. Conclusions ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.

Objective/background: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. Methods: This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. Results: Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III–IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667–199.255; p =

Adult patients with sickle cell disease (SCD) are highly susceptible to stem cell transplant complications, including drug toxicity, graft versus host disease (GVHD), and graft rejection due to SCD-related tissue damage, endothelial activation, and inflammation. The scarcity of compatible stem cells for transplantation further limits treatment options, with only 43 cases of adult allogeneic peripheral blood stem cell transplantation (allo-PSCT) from human leukocyte antigen (HLA)-identical sibling donors reported in the international registry for the period 1986-2013. Herein we report remarkable outcomes in a cohort of adult SCD patients who underwent allo-PSCT using a fludarabine (Flu), busulfan (Bu), and anti-T-cell lymphocyte globulin (ATG)-based conditioning regimen in combination with very low dose total body irradiation (TBI), followed by post-transplant cyclophosphamide (Cy) and sirolimus as GVHD prophylaxis. We performed a single-center, retrospective study consisting of 20 consecutive patients (mean age 33.4 years) who underwent allo-PSCT from HLA-matched related donors with a conditioning regimen of Flu 150/Bu 3.2/Cy 29/ATG 30 (Fresenius)/TBI 200 between September 2013 and September 2017. Data were validated by an independent data audit group of the affiliated JACIE-accredited transplantation center. All patients experienced a sustained donor cell engraftment. Full donor chimerism (total cell) occurred within 180 days in all patients. Mean duration of follow-up was 13.8 months (range: 0.3-50 months), with 12 (60%) patients completing 12 months. No non-relapse mortality or graft rejection occurred. Successful treatment was achieved without the presence of graft loss, grade III-IV acute GVHD, extensive chronic GVHD, or other major complications. Allo-PSCT in combination with Flu 150/Bu 3.2/Cy 29/ATG 30(Fresenius)/TBI 200- Cy/Sirolimus therapy yielded encouraging outcomes with no mortality and low incidence of GVHD. Further controlled studies will be necessary to compare transplant protocols and long-term outcomes.

Objective The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (

Background and Objective Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. Material and Method The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. Results Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. Conclusion G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions.

Although it is presumed to be a curative strategy for intermediate and high risk acute myeloid leukemia (AML), many patients relapse after allogeneic hematopoietic stem cell transplantation. This prompt us to examine the ways to improve the outcomes. We retrospectively evaluated 76 AML patients who were transplanted between 2007-2017 years in our clinic. We tried to identify the factors associated with posttransplant relapse, postrelapse survival and if there was a survival benefit of pretransplant consolidation and minimal residual disease (MRD) negativity. We examined the effect of the acute-chronic graft versus host disease (GVHD) and salvage therapy after the posttransplant relapses. The mean age of the patients was 44.6±1.21 years (ranges 21-67). 42.1% were females and 57.9% were males. 43.3% of the patients were in complete remission (CR) MRD positive state before the transplantation whereas 35.5% were in CR MRD negative and 3.9% were in progressive disease state. In 13 patients who were in CR state, the MRD status were not known. 11 (14.5%) patients were considered as in favorable risk, 52 (68.4%) in intermediate risk and 13 (17.1%) in unfavorable risk with respect to cytogenetic analysis before the transplantation. The donors were HLA compatible relatives (77.6%), HLA compatible non-relatives (10.5%), haploidentical people (9.2%), one HLA incompatible relative (1.3%) and one HLA incompatible nonrelative (1.3%). 74 bone marrow transplantations (97.4%) were allogeneic and the remaining two (2.6%) were autologous. Myeloablative conditioning regimen was applied to 57 patients (75%) and 19 patients got (25%) reduced intensity conditioning regimen. GVHD developed in 51.3% after transplantation and 61.5% of these were chronic extensive. Relapse occurred in 27 patients (35.5%), hematological relapse being the most common (31.6%). The median time for the development of relapse was found to be 5.5 months (range: 1.5-37). The overall probability for the development of a relapse was found to be 48.7% (95% CI: 40.9-56.5)(Figure1A). 23 patients (30.3%) died during the study period with a median survival of 9.6 months (range: 1.6-45). In the studied population the overall survival probability was found to be 52.8% (95% CI: 45.4 - 60.2) [Figure 1B]. 36.4%, 28.8% and 30.8% of the patients with favorable, intermediate and unfavorable cytogenetic status died respectively during the study period. The comparison of the survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status was depicted in Figure 2. The overall survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status were 46.6% (95% CI: 26.2-66.9), 54.6% (95 % CI: 45.9 - 63.2) and 36.9 % (95% CI: 25.4 - 48.5) respectively (p=0.807). MRD status of 60 patients were known. At the end of the study period 75.8% of the CR MRD positive and 70.4% of the CR MRD negative patients remained alive. The comparison of the survival of patients in CR with respect to MRD status is shown in Figure 3. The overall survival probability of CR MRD positive patients was 56.3 % (95% CI: 45.3 - 67.3) and this rate was 52.5 % (95% CI: 40.8 - 64.3) in MRD negative patients (p=0.770) [Figure 3]. Patients who developed GVHD had similar overall survival probability with the patients who did not developed the disease; 47.0% vs 57.2%, p=0.115 (Figure 4A). Even the patients with chronic extensive GVHD had similar overall survival rates with the patients who had none or acute GVHD; 49.3 % vs 58.2%, p=0.27 (Figure 4B). 66.7% of the patients with a progressive disease before the transplantation died during the study period and this rate was 27.1% in the patients with CR (p=0.005). In conclusion the overall survival rate of the transplanted AML patients was 52.8% in the study group. The overall survival did not seem to be affected by pre-transplant MRD status, cytogenetic risk factors and administration of consolidation therapy. The only patients who had significantly worse results were the ones who had progressive disease before the transplantation. From this point it would be logical to make transplantation whenever the patient is in first CR regardless of the MRD status and a matched donor is found so that the toxic effects of the consolidation chemotherapy may be prevented. Disclosures No relevant conflicts of interest to declare.

Multiple myeloma (MM) is a disease of the elderly. It shows rapidly increasing incidence with increased age. Although MM is rare in young people, patients diagnosed before the age of 50 years account for 10% of the overall incidence and approximately 2% are diagnosed before 40 years of age. The aim of the study was to assess the clinical results of the young MM patients diagnosed at the age of ≤45 years. All the MM patients who were ≤45 years old at the time of diagnosis and who were admitted to our clinic between January 2004 and December 2017 were retrospectively assessed. There was a total of 31 patients and 14 (45.2%) of them were females and 17 (54.8%) of them were males. The mean age was 40.4±3.8 years. The most frequent myeloma types were Ig G Kappa (n:12, 38.7%) and Kappa light chain (n: 10, 32.3%). The remaining types were Ig A lambda (n:4, 12.9%), Ig G lambda (n:2, 6.5%), Lambda light chain (n: 2, 6.5%) and non-secretory myeloma (n:1, 3.2%). Before transplantation 12 patients (38.7%) were in complete remission, 11 patients (35.5%) were in very good partial remission, 4 patients (12.9%) were in partial remission state and 4 patients (12.9%) had refractory disease. VAD + VCD protocol was given to 12 (38.7%) patients. 6 (19.8%) patients had VCD, 3 (9.7%) got VCD + VRD, 2 (6.5%) got VAD and 8 (25.8%) got other chemotherapy protocols. Transplantation was done in 26 patients (83.9%). Overall 9 patients (29%) died during the study period. Second or tandem transplantation was performed to 10 patients and 30% (n:3) of these re-transplanted patients died. The overall survival for these patients was estimated to be 70% (95% CI: 64.2-75.8). In conclusion MM in patients younger than 45 years is rare. In these patients Ig G Kappa and Kappa Light chain types are the most frequent types. Heterogeneous of individual patients may exist within these young myeloma patients. For those who are expected to show a poor response to current treatments despite their young age, the efficacy of an alternative therapeutic strategy such as front line allo-HSTC should be further investigated. Disclosures No relevant conflicts of interest to declare.