Mutation profile of the patients diagnosed with myeloid neoplasia tested with next generation sequencing and clinical implications

Aim: To analyze the distribution of gene mutations in myeloid neoplasias, based on next generating sequencing technology (NGS) and evaluate their clinical implications and impact on the risk stratification. Materials and Methods: 67 bone marrow samples which belong to 48 different patients who were diagnosed with myeloid neoplasia and tested with 30 gene myeloid panel by NGS in our center were evaluated retrospectively. Distribution of genomic alterations and clinical implications were compared in different groups. Results: Samples were separated into different groups according to the diagnostic categories. Most common diagnosis was acute myeloid leukemia (AML) with the rate of 58.3%. FLT3 mutation was the most common mutation in AML and whole population. After the incorporation of the NGS results into the prognostic classification in newly diagnosed AML group, 47.1% of the patients were up-staged or down-staged according to the European Leukemia Network (ELN) risk stratification system. Conclusion: Analyzing the mutation profiles with NGS in myeloid neoplasias has an important and remarkable effect on diagnosis and management of this group of diseases

Survival outcomes of hypomethylating agents maintenance therapy in new diagnosed AML patients: Real experience data

OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy that frequently affects elderly population. With introducing the hypomethylating agents (HMAs) in elderly AML treatment, survival rates and quality of life have improved. However, long-term management in elderly and frail patients is still a challenge. In the present study, we aimed to determine whether HMA maintenance therapy is required until disease progression in frail and elderly AML patients by examining with a real-life data.METHODS: In a multicenter study, we analyzed non-promyelocytic elderly AML patients who were treated with first-line azacitidine or decitabine monotherapy in two different groups, retrospectively. While patients were treated with HMA until progression in the maintenance group, 6+3 cycles of azacitidine or decitabine were administered as a standard care of elderly AML patients in the non-maintenance group. Survival outcomes were compared between the groups.RESULTS: HMA therapy was maintained until progression in 20 patients, and HMA therapy was terminated after 6+3 cycles in 21 patients. Patients received a median of 6 (1-14) HMA cycles during follow-up time. The median 7.5 months of overall survival were observed (2-17 months) in maintenance and 3 months (1-13 months) in non-maintenance groups (p=0.001).CONCLUSION: Despite long-term exposure to HMA may appear as a risk factor for complications and toxicities in elderly and frail AML patients, the maintenance of therapy until disease progression provides a significant survival advantage. Therefore, we suggest that HMA therapy should continue until disease progression regardless the sort of HMA

To rechallenge or not to rechallenge, that is the question? An unsuccessful attempt of hypomethylating agent plus venetoclax in an elderly FLT3-positive relapsed acute myeloid leukemia patient after a yearlong period of remission

Dear Editor, Acute myeloid leukemia is the most common sub-type of acute leukemia in adulthood [1]. It has a detrimental prognosis with conventional combination chemotherapy, mainly with anthracyclines and cytarabine. Allogeneic stem cell transplantation has signifcantly prolonged the overall survival in a particular “eligible” patient population, but as AML is a disorder of the elderly, not all patients are able to proceed with allogeneic stem cell transplantation

A case series of CML patients who were presented with isolated thrombocytosis

Per WHO 2016 and 2022 (5th ed.) myeloproliferative disease guidelines, Chronic Myeloid Leukemia (CML) is classified under two major groups according to the presence of bcr-abl translocation; these groups require different treatment approaches and show clinical presentation heterogeneity. Treatment agents such as tyrosine kinase inhibitors (Imatinib, Dasatinib, Nilotinib, Bosutinib, Ponatinib, Radotinib), Omacetaxine and Asciminib have been used in the treatment of Bcr abl positive CML according to the patient's clinic and mutation status. According to the IRIS study, a study evaluating CML patients treatment response to imatinib, the major molecular response was 33.3% at 3 months, the major molecular response was 48% at 6 months, and the major molecular response was 62.1% at 12 months; furthermore, the rate of achieving a complete molecular response at 12 months was 94.9% (4). In patients who was treated with imatinib as first line therapy, the rate of transformation to accelerated or blastic phase at 18 months was 0.9% in the MMR group and 9.9% in the non-MMR group. In "conventional" CML patients, high leukocyte counts may be accompanied by thrombocytosis; though presentation with only thrombocytosis without leukocytosis is hardly described so far. In this poster presentation, we introduced 7 cases who initially presented with isolated thrombocytosis and then diagnosed with Ph(+) CML. This study was conducted in three adult hematology centers from Antalya, Izmir and Istanbul. 400 patients followed in these centers were reviewed retrospectively; seven patients presented with isolated thrombocytosis were identified. Demographic characteristics, diagnostic findings, and risk scores of these patients were evaluated (Tablo 1). Eln 2013 response criteria were used for evaluation of response for 3rd, 6th, 12th. monthly responses (Figure 1). Here we present 7 CML patients without leukocytosis who were diagnosed with marked thrombocytosis. The patients had similar symptoms and physical examination with no obvious splenomegaly or thrombosis. All of the patients had minimal basophilia and normal peripheral smear findings. All patients responded well to imatinib therapy. During follow up patients who maintained their MMR achieve had a better clinical course and prognosis compared to other CML patients

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: First reported case

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare and challenging complication associated with poor prognosis and limited treatment options. Emerging T-cell directing therapies, such as bispecific antibodies (bsAbs) and chimeric antigen receptor T cells (CAR-T), have shown remarkable success in treating MM, but their efficacy in CNS involvement remains unclear. Elranatamab, a humanized bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3-expressing T cells, has demonstrated promising results in relapsed refractory MM. However, its efficacy in treating CNS-MM has not been reported. We present a case of a 37-year-old male MM patient with CNS involvement who has been successfully treated with Elranatamab

Assesment of patient's perspective on treatment free remission in CML: A Turkish multicenter cohort

Treatment free remission (TFR) is one of the main goals of therapy in Chronic Myeloid Leukemia (CML). Patient perspective and expectations have an indicative effect on discontinuation decisions. We analyzed 116 CML patients' perspective on TFR and factors that associated with willingness for tyrosine kinaz inhibitor (TKI) discontinuation from four different center in Turkey based on a national survey. Patients in our cohort had 7.8% awareness of TFR and after brief information willingness to attempt TFR has been reached to 58.9% in all population. Shorter disease duration was associated with enhanced willingness to attempt discontinuation in multivariate analyses (p=0.031). Most common patient related limitation for TKI discontinuation decision was anxiety about disease relaps and TKI resistance. Even disease relaps in TFR means molecular and detectable with close monitoring, patients still had considerable concerns about TKI discontinuation

Retrospective analysis of Turkish AML registry database, on behalf of AML working group of Turkish society of hematology

Abstract Introduction: To investigate the demographics and treatment details of the acute myeloid leukemia (AML) patients who were diagnosed and followed up in Turkey. Methods: Patients who were recorded on the database of Turkish AML Registry project were included in this study retro- spectively if they were diagnosed before 1st of Jan 2022. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented

Gilteritinib (XOSPATA (R)) in Turkey: Early access program results

Background And Objectives: Gilteritinib (XOSPATA (R), Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor, involved in both c-Kit and FMS-like tyrosine kinase 3 (FLT3) resistance. In the phase 3 ADMIRAL trial, gilteritinib was compared with the standard of care in (R/R) acute myeloid leukemia (AML) patients who harbored any FLT3 mutation and showed superior efficacy with regard to response and survival. Objectives: This research aimed to investigate the real-life efficacy and safety of gilteritinib in FLT3-positive R/R AML patients who were treated as a part of an early access program held in Turkey in April 2020 (NCT03409081). Results: The research included 17 R/R AML patients who had received gilteritinib from seven centers. The overall response rate was 100%. The most common adverse events were anemia and hypokalemia (7 patients, 41.2%). Grade 4 thrombocytopenia was observed in one patient only (5.9%), leading to permanent treatment discontinuation. Patients with peripheral edema had a 10.47 (95% CI: 1.64-66.82) times higher risk of death than those without peripheral edema (p<0.05). Conclusion: This research showed that patients with febrile neutropenia and peripheral edema were at a high risk of death when compared to patients without febrile neutropenia and peripheral edema

Hodgkin lenfoma hastalarında EORTC QLQ ile yaşam kalitesi değerlendirmesi: Çok merkezli çalışma

Aim: The aim of our study is to obtain data on the quality of life (QoL) in Hodgkin lymphoma (HL) patients in a representative sample of the general population of Turkey with the help of the EORTC QLQ-C30 and QLQ-HL27 questionnaires. Material and Methods: A total of 68 patients from seven different centers diagnosed with HL between 2018-2020 were included in the study. The questionnaires were answered cross-sectionally by the patient under the control of a physician in the centers participating in the study. Results: Out of 68 patients, 42.6% (n=29) were female and 57.4% (n=39) were male. The ages of the patients ranged from 18 to 74 years, with a mean of 42.10±16.62 and with a median value of 40 years. There was no significant difference between age subgroups in terms of QLQ-C30 global health status/ QoL, functional or symptom scales and HL27 SB, PC, EI and WF scores (p>0.05, for all). It was determined that the constipation scores of females were higher than the scores of males (p=0.041). No statistically significant difference was found in terms of HL27 SB, PC, EI and WF sub-dimension scores according to gender (p>0.05). Conclusions: There was only a statistically significant difference in terms of QLQ-C30 constipation sub-dimension scores according to gender. The constipation scores of females were higher than the scores of men. More detailed and large population studies are needed to reveal the effectiveness of QoL assessment in HL patients.Amaç: Çalışmamızın amacı, EORTC QLQ-C30 ve QLQ-HL27 anketleri yardımıyla Türkiye genelini temsil eden bir örneklemde Hodgkin lenfoma (HL) hastalarında yaşam kalitesi hakkında veri elde etmekti. Gereç ve yöntemler: 2018-2020 yılları arasında, HL tanısı almış yedi farklı merkezden toplam 68 hasta çalışmaya dahil edildi. Anketler, araştırmaya katılan merkezlerde hekim kontrolünde hasta tarafından yanıtlandı. Bulgular: 68 hastanın %42.6'sı (n=29) kadın, %57.4'ü (n=39) erkekti. Hastaların yaşları 18 ile 74 arasında değişmekte olup, ortalama 42.10±16.62 ve ortanca değeri 40 idi. QLQ-C30 global sağlık durumu/ yaşam kalitesi, fonksiyonel veya semptom skalaları ve HL27 SB, PC, EI ve WF skorları açısından yaş alt grupları arasında anlamlı fark yoktu (tümü için, p>0.05). Kadınların kabızlık puanlarının erkeklere göre daha yüksek olduğu belirlendi (p=0.041). Cinsiyete göre HL27 SB, PC, EI ve WF alt puanları açısından istatistiksel olarak anlamlı fark bulunmadı (p>0.05). Sonuç: Cinsiyete göre sadece QLQ-C30 kabızlık alt puanları açısından istatistiksel olarak anlamlı bir fark vardı. Kadınların kabızlık puanları erkeklerin puanlarından daha yüksekti. HL hastalarında QoL değerlendirmesinin etkinliğini ortaya çıkarmak için daha ayrıntılı ve geniş popülasyon çalışmalarına ihtiyaç olduğu görülmektedir

Comparison of efficacy and safety of generic plerixafor vs original plerixafor in the mobilization of myeloma patients

Introduction The commonest indication for an Autologous Stem Cell Transplantation (ASCT) is still Multiple Myeloma. A successful mobilization of hematopoietic stem cells (HSC) is a sine qua non of ASCT. The introduction of Plerixafor, which is a partial agonist of the alfa-chemokine receptor CXCR4 has added an important value and impact on mobilization. Plerixafor is successfully integrated into both growth factor-only and cyclophosphamide and growth factor mobilization strategies with significantly reducing the mobilization failure rate in myeloma patients. In addition, plerixafor + G-CSF has also been shown to successfully mobilize the majority of patients who previously failed to mobilize with either growth factor alone or in combination with chemotherapy. Even a Just-in-Time algorithm which induces plerixafor in patients who lacks a certain threshold of CD34 positive HSCs on the day of mobilization led to a cost-effective and successful mobilization with highly restricted rates of mobilization failure. In this study we tried to demonstrate the efficacy and safety of a novel generic Plerixafor (Pleksor - Gen Ilac) and to compare it with original one (Mozobil - Sanofi) in a retrospective manner. Method Patients who were transplanted in two centers who adopted the same mobilization standard operating procedures (SOP) were included in the study. An age and sex matched cohort of patients who received Mozobil (from 2020-2022 - Group A) were compared with the ones who received Pleksor (2021-2022 Group B) as a Just-in-Time conjunct to GCSF alone or chemo mobilization. Poor mobilization was defined as a final yield of 2 million CD34 positive HSCs per kg. Our aim was to collect enough stem cells for at least two ASCTs, thus our current SOP's indicated a minimum CD34 positive HSC threshold of at least 4 million per kg and an ideal HSC threshold of 6 million per kg. Results A total of 28 patients were included and they were equally distributed among Group A (n=14) and B (n=14). Median age of the patients at the time of mobilization were as follows, 60 (35-72) in Group A and 61 (38-70) in Group B. 14 patients who received Pleksor achieved a median yield of 8.40 million CD34 positive HSCs per kg (4.8-21) and the patients who received Mozobil have ended with a yield of 6.7 million CD34 positive HSCs per kg (4.5-13) (p=0.210). None of the patients in both groups were named to be a poor mobilizer according to the threshold of 2 million CD34 positive HSCs per kg but 3 of the patients in Group A and 2 of the patients in Group B ended with a yield of 6 million CD34 positive cells which was below to the ideal threshold for two transplants. Regarding lenalidomide exposure before mobilization, history of radiotherapy, line of the therapies received before mobilization, number of leukapheresis and the mobilization policy (chemo vs gcsf alone) there were no statistically significant difference between two groups (p=0.120, 0.702, 0.842, 0.769 and 0.420 respectively). The median neutrophil engraftment time in days were as follows for Group A and B, 11(10-14) vs 11 (10-16), p=0.541 and the median platelet engraftment time in days were 17 (10-30) in Group A and 16 (10-28) in Group B with a p value of 0.571. In none of the cases any specific side effects were noted which could be attributable to Pleksor or Mozobil. Conclusion Our study demonstrated a comparable efficacy of a generic form of Plerixafor when compared with the originator. This would lead to a decrease in the cost of total process of mobilization with a similar efficacy and toxicity profile. We are now planning to initiate a prospective trial to validate these results in a larger patient population. Up to our knowledge this is the first study comparing the efficacy of a generic Plerixafor in a sole myeloma patient cohort