Aims: Neutropenia, associated with several hereditary and acquired causes, is detected in a significant portion of patients presenting to the hematology outpatient clinic today. We conducted this study since we failed to find any Turkish publication on acquired isolated neutropenia in adults. Methods: This retrospective study examined data belonging to patients aged 18 years and older who applied to the adult hematology outpatient clinic whose absolute neutrophil count (ANC) was below the normal reference values (? 1.5 x 109/L). Results: 103 adult patients, 93 women and 10 men, were included in the study. Our study detected the cause of acquired isolated neutropenia as chronic idiopathic neutropenia (CINA) in 39.8% (n=41) of patients, autoimmune diseases in 18.4% (n=19), drugs in 14.6% (n=15), folate deficiency in 13.6% (n=14), infection in 9.7% (n=10), and hematological malignancy in 2.9% (n=3) and cyclic neutropenia in 1% (n=1). 92 patients (89.3%) were found to display mild neutropenia while 9 (8.7%) displayed moderate neutropenia and 2 (2%) displayed severe neutropenia. Interestingly, folate deficiency was detected in 6 of 9 (66.7%) moderately neutropenic patients. Conclusion: In our study, CINA was determined as the most common cause of acquired isolated neutropenia in adults, while autoimmune neutropenia was the second most common. In addition, the detection of folate deficiency in 6 of 9 patients (66.7%) with moderate neutropenia and the fact that these patients were in the advanced age group [mean 68 (range 62-81)] was a major finding of the study.

ABSTRACT BACKGRAUND Homeobox (HOX) transcript antisense RNA (HOTAIR) and HOX genes are reported to be more expressed in various cancers in humans in recent studies. The role of HOTAIR and HOXD genes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known. MATERIALS AND METHODS In this study, expression levels of HOXD8 , HOXD9 and HOXD11 from HOXD gene family and HOTAIR were determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR. RESULTS We determined that the expression levels of HOXD9 and HOXD11 in the AML patients were significantly lower than the control group (p<0.001 and p=0.002, respectively). There was no significant difference in the expression levels of HOTAIR and HOXD8 when compared to the control group. In the CML patients there was a significant increase in the expression level of HOTAIR when compared to the control group (p=0.002). The expression levels of HOXD9 and HOXD11 were found to be significantly lower than the control group (p<0.001). CONCLUSION Our study showed that HOTAIR may not be a biomarker in the diagnosis and is not significantly correlated with the clinicopathological prognostic characteristics of AML. Additionally; it can be said that HOTAIR is oncogenic by suppressing the expression of HOXD9 and HOXD11 but not HOXD8 in CML patients. The expression profiles of HOTAIR may be a potential biomarker in the diagnosis of CML patients in predicting and monitoring drug resistance.

Aims: Autologous peripheral blood stem cell transplantation (PBSCT), performed with high-dose melphalan support following induction therapy is still the gold standard method of treatment for multipl myeloma (MM)patients suitable for transplantation. It was aimed, with this retrospective study, to investigate the effects of early (1 day after PBSCT) and late (5 days after PBSCT) initiation of granulocyte colony-stimulating factor (G-CSF) support following PBSCT on engraftment time, febrile neutropenia, and length of hospital stay (LOS) in MM patients. Methods: This study included 70 patients with MM, who underwent PBSCT in Erciyes University. Two groups were administered 5µg/kg filgrastim, subcutaneously, either 1 day or 5 days after PBSCT, until neutrophil engraftment was reached. Results: Both neutrophil and platelet engraftment occurred in significantly shorter times in the early G-CSF group compared to late G-CSF group; the median times to neutrophil engraftment were 10 (8-13) and 11 (7-15) days, respectively, and the median times to platelet engraftment were 11 (10- 16) and 13 (11- 21) days (p=0.001). Also, the median LOS was also significantly shorter in the early G-CSF group compared to late G-CSF group; 14 (10-22) vs 16 (11- 33) days, respectively (p=0.016). No significant difference was found between the groups in terms of frequency of febrile neutropenia. Conclusion: The initiation of G-CSF support early, following PBSCT in MM patients, accelerated neutrophil and platelet engraftment and shortened the LOS as compared to the initiation of G-CSF support late, with no significant difference in the frequency of febrile neutropenia.

Objective:In this study, we aimed to obtain real-life data on the use of antimyeloma agents, which significantly increase overall survival (OS) in multiple myeloma (MM) patients, in primary plasma cell leukemia (pPCL) patients with poor prognosis. Materials and Methods:Data from 53 patients who were diagnosed with pPCL between 2011 and 2020 and who used at least one proteasome inhibitor (PI) and/or immunomodulatory (IMID) agent were analyzed retrospectively. Depending on the year of the pPCL diagnosis, 20% leukocytes or ≥2x109/L plasma cells in the peripheral blood was used as a diagnostic criterion. Results:The median age of the patients was 58 years and 23 (43.4%) patients were over 65 years of age. For first-line treatment, PI or IMID alone was used by 31 (58.5%) patients, and PI and IMID were used simultaneously by 15 (28.3%) patients. Additionally, 21 (39.6%) patients received transplantation and 13 (24.5%) patients received maintenance treatment. The median progression-free survival was 4 (range: 1-42) months. When patients whose primary disease was refractory to first-line therapy were excluded, the duration of treatment was 6.5 months. The median OS was 15 months with a median follow-up duration of 15 months. Only 7 (13.2%) of the patients were alive at the last follow-up visit. Those with higher β2-microglobulin levels and International Staging System stage 3 and non-transplant patients receiving first-line treatment had shorter OS (p=0.005, p=0.02, and p=0.008, respectively). The concomitant use of PIs and IMIDs, the addition of chemotherapy to induction therapy, and the response to induction therapy or maintenance therapy did not affect OS. Conclusion:In this study, as in previous similar studies, we could not see an increased survival trend in pPCL, which is observed in MM. New studies are needed for pPCL, which is likely to increase with new diagnostic criteria, based on current agents and information from MM.

Introduction: Cytomegalovirus (CMV) is an important cause of mortality and morbidity in patients with immune defects. Due to the extensive use of immunosuppressive treatments, CMV infections have emerged as one of the most critical problems for patients with hematological malignancies globally.CMV infections can lead to life-threatening CMV-related diseases and graft rejections after bone marrow transplantation. It is more difficult to determine the incidence and risk factors of CMV infection in non-transplanted patients. The purpose of this study was to evaluate the frequency of CMV reactivation and risk factors of CMV disease in chemotherapy-treated patients who did not get stem cell transplantation. Materials and Methods: This was a prospective, single-center study involving 316 non-transplanted adult patients receiving chemotherapy for hematologic malignancies. Patients diagnosed with leukemia and lymphoma who developed neutropenia for more than 3 days after chemotherapy were included in the study. After chemotherapy, CMV PCR follow-up was routinely performed 2 days a week during their hospitalization. CMV DNA was investigated by real-time PCR method. CMV-DNA follow-up results and clinical evaluations of the patients were reviewed. The relationship between CMV reactivation and clinical and demographic parameters of the cases was investigated. Results: There were totally 504 hospitalization episodes of 316 patients. CMV PCR was studied in all hospitalization episodes. CMV infection incidence of 316 patients was 9%. CMV viremia was observed in 35 of 504 hospitalization episodes, and CMV viremia and disease were observed together in 13. Of the 13 episodes with CMV disease, 4 were CMV retinitis and 9 were CMV pneumonia. Antiviral therapy was given for a total of 29 episodes. Of the 48 episodes with CMV viremia, 16 (33%) received preemptive treatment, while 13 (27%) received treatment for CMV disease. Ganciclovir was given to all patients as preemptive treatment. Ganciclovir was administered as antiviral therapy in 13 episodes with both CMV viremia and CMV disease. 19 episodes (40%) with CMV viremia were followed without antiviral treatment. Of the 29 episodes that received antiviral therapy for CMV viremia, 13 (45%) recovered with antiviral therapy, while 3 (10%) died despite receiving antiviral therapy. PCR positivity continued in 13 (45%) patients, but CMV disease did not develop in these patients during follow-up. CMV viremia was present in 25 (7%) episodes with a diagnosis of leukemia and 23 (14%) with a diagnosis of lymphoma. There was a significant difference in the frequency of CMV viremia between these two groups (p=0.035). While CMV disease was observed in 5 (2%) episodes with a diagnosis of leukemia, it was found in 8 (5%) episodes with a diagnosis of lymphoma. There was a significant difference in the frequency of CMV disease between these two groups (p=0.038). Both cmv viremia and cmv disease were statistically higher in refractory disease (p=0.006, p=0.016). In the univariate analysis, diagnosis of lymphoma, refractory disease, administration of >2 lines of chemotherapy, rituximab based therapy, lymphopenia before neutropenia, lymphopenia after neutropenia, and co-infection were independent risk factors for CMV viremia. However, in the multivariate analysis, only post-neutropenia lymphopenia and co-infection status were independent risk factors for CMV viremia. The risk of developing CMV in patients with lymphopenia after neutropenia was 3.1 times higher than those without lymphopenia (p=0.011), and it was 6.4 times higher in those with co-infection than in those without (p=0.013). Co-infection was seen in 402 (80%) of 504 hospitalization episodes. There was a statistically significant correlation between CMV viremia and co-infection. (p=0.002). However, no significant relationship was found between CMV disease and co-infection (p=0.081). Conclusion: This real-life experience shows that CMV infection can become a serious threat for patients with hematological malignancies during the period of intensive chemotherapeutic regimen. We think that our study, which reflects the experience of a single center, is important in terms of monitoring CMV in patients with hematological malignancies who did not undergo transplantation.

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is a birth defect of the blood vessels that causes telangiectasias and arteriovenous malformations. HHT is a rare, autosomal dominant vascular disorder affecting approximately 1 in 8000 people. This multisystem angiogenic disorder is genetically and phenotypically variable, with the most common symptom being severe and recurrent epistaxis. ALK1, TGF-ß, and VEGF are involved in its pathogenesis. VEGF increases mitotic activity in vascular endothelial cells, leading to uncontrolled angiogenesis and the formation of fragile vessels. Bevacizumab is used in the treatment of HHT by inhibiting VEGF. We present our patient, who developed hepatic encephalopathy due to hemorrhages with diffuse telangiectasias of the skin and tongue due to HHT and achieved an effective response to both conditions with bevacizumab.

Danger-associated molecular patterns (DAMPs) are molecules that can initiate and maintain robust inflammatory responses and were investigated in the pathogenesis of graft versus host disease (GvHD). Uric acid (UA) and fibrinogen (Fib) are DAMPs released from damaged tissue during allogeneic hematopoietic stem cell transplantation (allo-HCT) and GvHD. We aimed to evaluate the effects of UA and Fib levels on survival in GvHD. One hundred seventy-four patients with grade 2-4 acute GvHD were included. UA and Fib levels were evaluated on allo-HCT day 0 and GvHD on days 0, 7, 14, and 28. Fib GvHD day 0 was the independent predictor for overall survival (OS), non-relapse mortality (NRM), and progression-free survival in multivariable models (HR 0.98, p < 0.001; HR 0.98, p = 0.001, HR 0.98, p = 0.006, respectively). Also UA GvHD day 28 was the independent predictor for OS and NRM (HR 0.77, p = 0.004; HR 0.76, p = 0.011, respectively). Our results indicated that hypouricemia and hypofibrinogenemia were associated with a significantly shorter OS and higher NRM. UA and Fib are remarkable molecules in GvHD because they are routinely utilized, readily available, can be therapeutic targets, and have DAMPs and antioxidant features.

Acute leukemias, particularly acute lymphoblastic leukemia (ALL) and, to a lesser extent, acute myeloid leukemia (AML), remain among the most challenging hematologic malignancies due to high mortality rates and limited treatment options. In this context, Chimeric Antigen Receptor T (CAR-T) cell therapy has emerged as a promising approach for patients with refractory or relapsed disease.CAR-T cells are generated by genetically engineering the patient's T cells to express synthetic receptors targeting specific tumor-associated antigens. In ALL, CD19-targeted CAR-T cell therapies have demonstrated complete remission (CR) rates of 70–90%. For AML, ongoing research is exploring alternative targets.Clinical Studies and OutcomesELIANA TrialThe ELIANA trial, the largest global multicenter study of CD19-targeted CAR-T therapy, focused on pediatric and young adult ALL patients Tisagenlecleucel was infused into 75 ALL patients and evaluated for efficacy. The overall remission rate at 3 months was 81%, and all patients who responded to treatment were found to be negative for minimal residual disease by flow cytometry. Event-free survival and overall survival rates were 73% and 90% at 6 months and 50% and 76% at 12 months, respectively. Median duration of remission was not achieved. Tisagenlecleucel persisted in the blood for up to 20 months. Grade 3 or 4 adverse events thought to be related to tisagenlecleucel occurred in 73% of patients. Cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurological events occurred in 40% of patients and were managed with supportive care, and no brain edema was reported.ZUMA-3 TrialThe ZUMA-3 an international, multicentre, single-arm, open-label study evaluating the efficacy and safety of the autologous anti-CD19 CAR-T-cell therapy KTE-X19 in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia. KTE-X19 was administered to 55 (77%) patients. At a median follow-up of 16.4 months (13.8-19.6), 39 patients (71%; 95% CI 57-82, p<0.0001) had CR or CRi and 31 (56%) achieved CR. Median duration of remission was 12.8 months (95% CI 8.7 - not estimable), median relapse-free survival was 11.6 months (2.7-15.5) and median overall survival was 18.2 months (15.9 - not estimable). Among responders, median overall survival was not reached and 38 (97%) patients had MRD negativity. Ten (18%) patients received allo-SCT consolidation after KTE-X19 infusion. The most common adverse events of grade 3 or higher were anemia (27 [49%] patients) and pyrexia (20 [36%] patients). 14 (25%) patients had grade 3 or higher infections. Two grade 5 KTE-X19-related events occurred (cerebral herniation and septic shock). Grade 3 or higher cytokine release syndrome occurred in 13 (24%) patients, and grade 3 or higher neurologic events occurred in 14 (25%) patients.AML Target StudiesAML poses unique challenges due to its heterogeneous cell populations. Early-phase studies of CD33-targeted CAR-T cells have shown promising tumor burden reductions in specific patient cohorts. However, these studies are still in the clinical validation phase.Future PerspectivesNext-generation CAR-T cell designs aim to enhance target specificity and minimize adverse effects, improving the therapy's safety and efficacy profile. Allogeneic CAR-T platforms and universal CAR-T cell technologies are also under development, potentially increasing accessibility for a broader range of patients.In conclusion, CAR-T cell therapy represents a transformative step in personalized treatment strategies for acute leukemias. Continued advancements in clinical trials and translational research will further unlock the potential of this innovative approach in hematology.

Background and AimChronic myeloid leukemia (CML) incidence has recently increased in younger individuals. With time, given the nature of the disease and available therapies, as well as the existing paucity and inconsistency of advice, worries about fertility have surfaced. With all these clear unknowns, we designed this study to raise awareness among both physicians and CML patients about whether male and female patients of childbearing age were using contraception at the time of diagnosis, and if so, which methods they were using. In this context, this study aimed to evaluate the contraception methods in patients with CML.Materials and MethodsEighteen centres from Turkey participated in the study. Male and female patients of childbearing age diagnosed with chronic and accelerated phase CML between the years 2000 and 2024 were evaluated retrospectively.ResultsOf the two hundred and thirty-two patients included, one hundred and twenty-five (53.9%) of these patients were female and 107 (46.1%) were male. At diagnosis, all female patients were in the childbearing age, and male patients were sexually active. The median age at diagnosis of the patients was 38 (range, 18-77) years. Eighty-six (68.8%) female patients were using any contraception method, while this was 53.2% (n = 57) among male patients.ConclusionIn conclusion, since CML patients are diagnosed at an earlier age and the desire of these patients to have children, adequate information and evaluation should be provided regarding fertility and contraception issues, especially in female patients, from the moment of diagnosis.

Background and Aims: Venetoclax is an important treatment option, especially in patients who are unfit for acute myeloid leukemia treatment. However, because venetoclax is metabolized by CYP3A4, it can lead to many drug-drug interactions (DDIs). DDIs may make a drug less effective, cause unexpected side effects, or increase the action of a particular drug. This study aims to examine venetoclax-related DDIs in this vulnerable patient population and to illuminate possible interventions for both patients and clinicians. Methods: This observational study was performed between November 2018-December 2022 in the Department of Hematology, Erciyes University Faculty of Medicine. The study involves 60 patients and uses Lexi-interact (R) to determine potential DDIs (pDDIs) in all patients and uses Lexi-interact (R) to take into account category D and category X interactions. Results: Forty-seven (78.4%) patients experienced drug interactions. The most common drug interactions were with azole antifungals, most commonly with posaconazole in category D (31.6%). Clarithromycin and diltiazem were found in more than 20% of patients. Carbamazepine, phenytoin and cladribine were found as contraindicated (category X) drugs. Conclusion: The study shows that at least 78.4% of the patients treated with venetoclax were at risk of DDIs. Dose reduction of venetoclax is necessary when used with azole antifungals. Due to the extremely high occurrence of DDIs, pharmacists have a significant role in drug interaction management in the multidisciplinary team.

BACKGROUND:Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure. METHODS:In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not. RESULTS:Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 106/kg in the DM group, while it was 8.2 (1.7-37.3) × 106/kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02). CONCLUSION:DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients.

Background: It is evident that treatment outcomes improve with the clinical studies, in this study we aimed to investigate the demographics and treatment modalities of the acute myeloid leukemia (AML) patients in a large population-based cohort who were diagnosed and followed up in Turkey as a real-world data. Methods: All AML adult patients who were recorded on the database of Turkish AML Registry project from 25 sites were included in this study if they were diagnosed before 1st of June 2022. Study approved by ethics committee and Ministry of Health of Turkey. Demographics and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 906 patients were included in the study, 891 patients data accepted as adequate and underwent further evaluation. Median follow-up period was 12.0 (SD:26.6) months and 45.4% of the patients were female. Median age at the time of diagnosis was 58 (18-91). According to the FAB classification most common subtypes were M4 (23.6%), M2 (21.6%), M5 (16.8%) and M1 (13.5%) and AML, NOS (36.9%) is the most common type according to the WHO classification. Of the patients 60.8%, 24.7%, 14.5%, was intermediate, favorable and poor respectively considering AML risk stratification (ELN 2017) by genetics. Only 4.4% of the patients had extramedullary involvement. For the first induction 70.8% of the patients had received intensive regimens composing anthracyclines and ARA-C and for the first relapse 71.8%. ARA-C (71.7%) backbone and Azacitidine alone (13.4%) are the most used regimens, 10.5% and 22.5% underwent allo-HCT during the first and second induction respectively. Response rates obtained by the induction therapies were as follows; 61.7% CR (including 9.3% MLFS), 14.2% PR, 8.6% SD, 15.5% PD, the ratio was 59.7% and 24.3% for CR2 and PD respectively. Median overall survival has not been reached for the favorable risk group, were 16.2 months for the intermediate risk and 14.1 months for the poor risk group (p<0.001) and 22.7 months for the entire population. Median progression free survival were 32.6 months for the favorable risk group, 12.7 months for the intermediate risk and 9.4 months for the poor risk group (p<0.001) and 15.2 months for the entire population (Figure 1). COX regression analysis were performed for the prognostic factors of OS, univariate analysis performed with the parameters; age (<60 and ≥60), FAB classification, ECOG, FLT3, NMP1, HCT were accepted as clinically significant covariates. First univariate then with the significant parameters (p<0.05) multivariate COX regression analysis were perfomed. With the multivariate analysis age (p:0.005, HR:2.140, 95% CI: 1.254-3.653), FAB classification (favorable were reference, intermediate p:0.045, HR: 2.269, 95% CI: 1.017-5.064, poor p:0.217, HR: 2.105, 95% CI: 6.858) and HCT (p:0.034, HR:2.618, 95% CI: 1.073-6.387) were found as significant. Conclusion: Progression free survival obtained after induction therapy and overall survival were relatively shorter than the ones which were presented by other real-world registries. Lack of early access to the targeted and novel agents, like Flt3 inhibitors, Venetoclax, IDH1 and 2 inhibitors, CPX351 and Glasdegib should be a potential explanation to this relatively short PFS and OS. We have also been aware of un-ideal access to well established and nation wide cytogenetic laboratory service to induce early integration of targeted agents to the treatment and better risk stratification to determine the patients who should obtain the best prolonged survival via allo-HCT.

Purpose: Clofarabine is a second-generation purine analog that inhibits DNA synthesis. It is used as an effective new agent in relapsed refractory acute leukemia. We aimed to report our single center experience about CLOVE protocol as a clofarabine-based regimen in patients with relapsed or refractory T-cell acute lymphoblastic leukemia. Materials and Methods: Thirteen patients with relapsed or resistant T-cell acute lymphoblastic leukemia were included in this study. Patients were administered clofarabine (40 mg/m2/day), etoposide (100 mg/m2/day), and cyclophosphamide (440 mg/m2/day) (5 days chemotherapy). The patients' data were reviewed retrospectively, the demographic and clinical characteristics of patients were recorded. Results: The patients' median age was 47, and 77% (n:10) of them were male. The median number of chemotherapy regimens they received before clofarabine was 3. Of the patients, 54% (n=7) presented with relapse, and 46% (n=6) with refractory disease. Hematological side effects were observed in all patients during treatment, and 4 (31%) patients were complicated by febrile neutropenia. Other side effects were hepatotoxicity 39%, skin reaction 2%, nausea 54%, and mucositis 31%. Three (23%) patients were unresponsive to treatment. A response was obtained in 10 (77%) patients. Allogeneic stem cell transplantation was performed in 4 of 5 patients with complete response. The median follow-up time after CLOVE was 2.3 (0.69-26.02) months. The median estimated survival time was 21.04 ± 3.88 (95%CI: 13.43 -28.64) months. Overall survival was 85.7% at three months and 57.1% at one year. Three patients were alive at the end of our study. Conclusion: The combination of clofarabine, etoposide, and cyclophosphamide (CLOVE) appears to be successful in achieving a response in relapsing or resistant acute leukemia. However, more effective regimens are still needed.

Aim: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still one of the most effective treatments for many hematological malignancies. However, especially infections and neutropenic fever increase mortality during the engraftment development process after allo-HSCT. This study investigated the effect and safety profile of granulocyte transfusion (GT) on engraftment in patients with neutropenic fever after allo-HSCT. Material and Method: We investigated 32 patients with hematological malignancies who had neutropenic fever following allo-HSCT between June 2018 and February 2020. Seventeen patients were given GT and defined as GT group (GTG). GT was given once daily until improvement in clinical and laboratory parameters (neutrophil >0.5 ×10³/µL, platelet >20 ×10³/µL). Fifteen patients who did not receive GT were included as a control group (CG). Results: By comparing leukocyte levels between the start and end of GT, the median leukocyte increase was shown as 1.93 (0.37- 10.21) ×10³/µL (p=0.001). Similarly, the median neutrophil increase was 1.14 (0.25-9.24) ×10³/µL (p=0.001). A total of 65 GTs were administered, the average number of days was 4±1. The average dose of infused granulocyte was 4 ×1010/unit. In GTG, neutrophil and platelet engraftments occurred on average at 14±2 and 10±2 days, respectively. In CG, neutrophil and platelet engraftments occurred on average 15±2 and 12±3 days, respectively. There was no statistically significant difference in neutrophil and platelet engraftment between the two groups (p=0.4, p=0.06, respectively). Conclusion: GT was observed to be effective in managing complications such as neutropenic fever and sepsis after allo-HSCT by shortening the duration of neutropenia and increasing neutrophil and leukocyte values. Although statistical significance was not observed in our study, it was observed that the engraftment times were shortened with GT.

Aim: It is known that the prognosis of acute leukemia patients who relapse after the first allogeneic stem cell transplantation (ASCT) is dismal. Our goal was to assess the value of a second allogeneic stem cell transplant in acute leukemia patients who experienced post-transplant recurrence. Material and Methods: We retrospectively reviewed data from 29 patients with relapsing acute leukemia who underwent a second ASCT. Nineteen patients with acute myeloid leukemia and ten patients with acute lymphoblastic leukemia were included in the study. Results: Ten AML patients and 10 ALL patients were included in the study. Most patients (62%) were in remission before the second transplantation. The median time between the first and second ASCT was 11.9 months (3.1-42 months). Complete remission (CR) was achieved after the second ASCT in 21 (72%) patients, and 11 (52%) patients relapsed after the second ASCT. During this analysis, six patients (21%) were alive and in remission. Relapse of the disease was the leading cause of mortality. After the second ASCT, overall survival (OS) was 6.34 months, and leukemia-free survival (LFS) was 13.8 months. Conclusion: For patients with acute leukemia who relapsed after the first ASCT, a second ASCT is a good option and can keep patients alive.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3–4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3–4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9

Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. HHCS is a rare disease characterized by high serum ferritin levels, congenital bilateral cataracts, and the absence of tissue iron overload. In this case report, we aimed to present a young female patient with a history of cataracts in herself and her family members. Our patient had the dilemma of iron deficiency anemia and hyperferritinemia. As in our patient, patients with HHCS apply to many outpatient clinics and have difficulty in diagnosis. For this reason, we prepared our case to raise awareness.

Introduction: Standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) includes a combination of standard-dose cytarabine and an anthracycline (idarubicin [IDA], daunorubicin [DNR], or mitoxantrone [MXR]). Anthracycline selection is still not standardized, and the impact of anthracycline selection on survival and response in patients with adverse genetic risk is of interest. The study aimed to retrospectively compare the effectiveness of induction regimens with respect to anthracycline preference. Methods: The study population was recruited from the Turkish AML Registry project database based on documentation of newly diagnosed AML and induction chemotherapy with IDA, DAU, or MXR in combination with cytarabine. Patients diagnosed before 31 August 2022 were received typical “7 + 3” induction chemotherapy containing 3 days of IDA, DAU, or MXR. Results: The study included 317 newly diagnosed AML patients (median age 51; range, 18 - 79; 55.2% male). Of the patients, IDA was administered in 266 (83.9%), DNR in 42 (13.2%), and MXR in 9 (2.8%). The three anthracycline treatment groups were similar between age, gender, type of AML by the World Health Organization (WHO), and risk classification by 2017 European LeukemiaNet (ELN) when evaluated according to the baseline disease characteristics. At the time of diagnosis, although the median white blood cell levels were 19 x 10 9/L (0.4 - 355) in the IDA, 7.8 x 10 9/L (0.7 - 357.2) in the DAU, and 5.5 x 10 9/L (0.6 - 34) in the MXR therapy group (p = 0.019); the hemoglobin and platelet levels and bone marrow blast percentage were similar between the treatment groups. FMS-like tyrosine kinase-3 internal tandem duplication ( FLT3-ITD) (p = 0.561) and Nucleophosmin 1 gene ( NPM1) (p = 0.430) mutation frequencies were also similar between treatment groups. Morphological complete remission (CR) was documented in 65% of all evaluable patients. Among the patient groups, CR was 67.7% for IDA, 50% for DNR, and 55.6% for MXR (p = 0.081). In univariate analysis (Table 1), significant predictors of overall survival (OS) were age ≥60 years (p <0.001), acute leukemias of ambiguous lineage (p <0.001), presence of disseminated intravascular coagulation (DIC) (p = 0.012), and FLT3-ITD mutation (p = 0.018); no significant interaction was noted between NPM1 mutation and OS (p = 0.059). Additionally, when idarubicin was taken as a reference, there was no meaningful relationship between anthracycline type and OS (p values for daunorubicin and mitoxantrone were 0.145 and 0.356, respectively). In multivariate analysis (Table 1), age ≥60 years (p = 0.001), acute leukemias of ambiguous lineage (p = 0.007), and the presence of DIC (p = 0.040) remained significant. After a median follow-up of 29.8 months, 32.5% relapse cases were documented and similarly distributed among IDA (33.1%), DNR (31%), and MXR (22.2%) therapy groups (p = 0.771). During the same period, allogeneic hematopoietic stem cell transplantation (AHSCT) was documented in 10.9% and 26.2% of patients treated for IDA and DNR, respectively. No patient progressed to AHSCT in the MXR arm (p <0.001). In the study, 142 (44.8%) deaths were reported, and there was a 48.5%, 26.2%, and 22.2% mortality rate between the IDA, DNR, and MXR treatment groups, respectively. There was no significant difference in OS by anthracycline type in both the study cohort and age group <60 years (Figures 1A and 1B). There was also no significant difference in OS in patients with the adverse genetic risk group and <60 years age group with adverse genetic risk, according to 2017ELN (Figures 1C and 1D). The results may have been influenced by the number of patients in the treatment groups of the retrospective study and by differences in fitness levels that needed to be measured systematically. Conclusions: We are encouraged that our findings mostly agree with previously published studies and that IDA, DNR, and MXR offer comparable survival values in the research and the younger patient groups. In the future, the ever-changing treatment environment in patient groups with targetable mutations makes choosing the optimal anthracycline for induction chemotherapy in AML much more difficult.

INTRODUCTION:Fludarabine, a purine analog, is getting more attention with the increasing use of reduced intensive conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The side effect of bradycardia was observed in only a few cases reported in the literature. In clinical practice, bradycardia can be asymptomatic or cause syncope and cardiac arrest. This study aimed to evaluate the bradycardia side effect of fludarabine used in the conditioning regimen in allo-HSCT recipients and to increase awareness of this issue. METHODS:This retrospective study included 73 patients who received fludarabine in the allo-HSCT conditioning regimen between January 2015 and January 2021. Patients with and without bradycardia were compared regarding demographic data, allo-HSCT characteristics, electrolyte values, fludarabine administration dose and duration, and survival. Univariate and multivariate analyzes were performed to evaluate independent predictors for fludarabine-induced bradycardia. RESULTS:Fludarabine administration doses and days were higher in the bradycardia group, but no statistically significant difference was observed. In the multivariate analysis, age was the only independent predictor of fludarabine-induced bradycardia (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.89-0.98, p = 0.007). The median age in the group with bradycardia was 19 years younger than those without bradycardia (34 (19-49) vs 53 (19-69), p = 0.005). In 11 (84.6%) of the patients who had bradycardia, bradycardia improved with the discontinuation of fludarabine alone, but atropine was administered in 2 (15.4%) patients. CONCLUSION:Age was the only independent predictor of fludarabine-induced bradycardia; therefore, close heart rate monitoring is recommended during fludarabine administration, especially in younger patients.

Purpose: Clofarabine is a second-generation purine analog that inhibits DNA synthesis. It is used as an effective new agent in relapsed refractory acute leukemia. We aimed to report our single center experience about CLOVE protocol as a clofarabine-based regimen in patients with relapsed or refractory T-cell acute lymphoblastic leukemia.Materials and Methods: Thirteen patients with relapsed or resistant T-cell acute lymphoblastic leukemia were included in this study. Patients were administered clofarabine (40 mg/m2/day), etoposide (100 mg/m2/day), and cyclophosphamide (440 mg/m2/day) (5 days chemotherapy). The patients' data were reviewed retrospectively, the demographic and clinical characteristics of patients were recorded.Results: The patients' median age was 47, and 77% (n:10) of them were male. The median number of chemotherapy regimens they received before clofarabine was 3. Of the patients, 54% (n=7) presented with relapse, and 46% (n=6) with refractory disease. Hematological side effects were observed in all patients during treatment, and 4 (31%) patients were complicated by febrile neutropenia. Other side effects were hepatotoxicity 39%, skin reaction 2%, nausea 54%, and mucositis 31%. Three (23%) patients were unresponsive to treatment. A response was obtained in 10 (77%) patients. Allogeneic stem cell transplantation was performed in 4 of 5 patients with complete response. The median follow-up time after CLOVE was 2.3 (0.69- 26.02) months. The median estimated survival time was 21.04 & PLUSMN; 3.88 (95%CI: 13.43-28.64) months. Overall survival was 85.7% at three months and 57.1% at one year. Three patients were alive at the end of our study.Conclusion: The combination of clofarabine, etoposide, and cyclophosphamide (CLOVE) appears to be successful in achieving a response in relapsing or resistant acute leukemia. However, more effective regimens are still needed.