Validity and reliability of the Turkish version of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) quality of life questionnaire in patients undergoing bone marrow transplantation.

OBJECTIVE: The Functional Assessment of Cancer Therapy-Bone Marrow Transplant Version 4 (FACT-BMT) is a widely used instrument to assess quality of life in individuals treated with bone marrow transplantation (BMT). Our aim was to determine the reliability and validity of the Turkish version of the FACT-BMT in patients undergoing BMT. METHOD: Patients between the age of 20 and 65 years and who had undergone BMT at least 3 months before the study were included. Validity was determined using exploratory and confirmatory factor analysis. To determine convergent validity, the European Cancer Research and Treatment Organization Quality of Life Questionnaire-Cancer30 (EORTC QLQ-C30), the Brief Fatigue Inventory (BFI), and the Eastern Cooperative Oncology Group (ECOG) performance score were used. Cronbach's alpha, intra-class correlation coefficient (ICC), and item-total correlation (ITC) values were calculated to assess the reliability of the FACT-BMT. RESULTS: Totally, 114 patients (F/M: 47/67) treated with BMT (mean age: 49.50 ± 12.50 years) were included. Confirmatory and exploratory factor analysis revealed that the FACT-BMT and the Bone Marrow Transplantation Subscale (BMTS) had sufficient fit. The FACT-BMT was moderately to strongly correlated with the EORTC QLQ-C30, the BFI, and the ECOG performance score (p < 0.001). Cronbach's alpha and ICC values of the FACT-BMT were acceptable (0.925 and 0.956, respectively). The ITC values of each item of the FACT-BMT were also acceptable (ranged from 0.296 to 0.737). Patients undergoing autologous BMT had a significantly higher BMTS score than those undergoing allogeneic BMT (p < 0.05). SIGNIFICANCE OF RESULTS: The Turkish version of the FACT-BMT is valid, reliable, and sensitive to changes in quality of life in patients undergoing BMT.

Bone Marrow Origin of Coronary Artery Diseases: The Impact of the Local Renin-Angiotensin System.

The renin-angiotensin system (RAS) has both important systemic circulatory and local effects. The effects of local cardiac RAS on the cardiovascular system have been increasingly researched. In this study, we review the relationship between local bone marrow and local cardiac RAS and their impacts on atherosclerosis.

Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia.

OBJECTIVE: Aplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center. METHODS: Twenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively. RESULTS: The median follow-up time was 95.2 months (range, 4.8-235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9-16 days) and 13 days (range, 11-29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection. CONCLUSION: Although there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.

The clinical course of COVID-19 in hematopoietic stem cell transplantation (HSCT) recipients

Background/aim: The disease caused by SARS-CoV-2 was named as COVID-19. There is as yet insufficient information about the effects of HSCT on the clinical course of COVID-19. In the present study, we aimed to investigate the clinical course of COVID-19 in patients who had undergone HSCT. Materials and methods: We analyzed baseline characteristics, clinical course and findings of COVID-19, hospitalization and death rates, overall survival, and case fatality rates of HSCT recipients diagnosed with COVID-19 retrospectively. Results: 57.6% of the patients underwent AHSCT, and 42.4% underwent allo-HSCT. 60.6%, 27.3%, and 12.1% of the patients had mild, moderate, and severe COVID-19 or critical illness, respectively. Overall, 45.5% were hospitalized, 12.1% required intensive care, and 9.1% necessitated invasive mechanical ventilation. The total CFR was 9.1% in HSCT recipients, 22.2% in patients with active hematologic malignancy, and 4.2% in patients without active hematologic malignancy. Conclusion: It can be concluded that mortality of HSCT recipients is lower in patients whose primary disease is in remission compared to ones that are not in remission. Further studies with larger group patients are needed in order to delineate the effects of COVID-19 on HSCT patients.

Assessment of Diastolic Function and Thiol-Disulphide Homeostasis in Arsenic-Exposed Workers.

OBJECTIVES: Exposure to arsenic is associated with various cardiovascular diseases. The imbalance between antioxidant and oxidant homeostasis plays a crucial role in the cardiovascular effects of arsenic. The aim of this study was to investigate the effect of arsenic exposure on diastolic function by measuring thiol and disulphide in arsenic-exposed workers. METHODS AND RESULTS: A total of 107 male arsenic-exposed workers and 36 healthy subjects were enrolled. Mitral inflow velocity and parameters of diastolic function were measured. As oxidative stress indicators, total thiol, native thiol, disulphide, and their percent ratios were determined. The mean age was 39.1 ± 9.5 years in the arsenic-exposed group and 37.4 ± 9.6 years in the controls. The median blood arsenic level was 42 µg/dL in the arsenic-exposed group and 3.75 µg/dL in the controls. E-wave, E/A ratio, and e' wave were lower and left atrial diameter, A-wave, average E/e' ratio, and tricuspid regurgitation velocity were higher in the arsenic-exposed group. Native and total thiol concentrations were lower, and disulphide/native and disulphide/total thiol ratios were higher in the arsenic-exposed group. Fourteen (13.1%) workers had diastolic dysfunction, 26 (24.3%) had indeterminate, and 67 (62.6%) had normal diastolic function, compared to 1 (2.8%), 2 (5.6%), and 33 (97.7%) in the control group, respectively. In regression analysis, disulphide/native thiol ratio (p < 0.001) and blood arsenic level (p < 0.001) predicted increased average E/e' ratio in the arsenic-exposed group. CONCLUSIONS: This study showed strong associations among arsenic exposure, oxidative stress, and diastolic function, and revealed the influence of arsenic exposure on diastolic dysfunction through oxidative stress.

Cardiac adverse events during stem cell transplantation for hematological malignancies: A single centre experience.

Hematopoietic stem cell transplantation (HSCT) is a highly successful treatment option for many hematological malignancies. Several adverse effects can be seen in HSCT due to the infusion and damage caused by the conditioning regimens. Cardiovascular adverse effects are relatively common during HSCT, and they have the potential to cause devastating complications. The aim of present study was to evaluate the transplantation-related cardiac adverse effects and determine the risk factors in patients undergoing HSCT at our institution. A retrospective analysis has been performed in 662 patients who was treated at Hacettepe University Stem Cell Transplantation Unit. Amongst the 622 patients, 318 (51.1 %) underwent autologous and 304 (48.9 %) underwent allogeneic HSCT. The frequency of the cardiac adverse effects was found to be 10.8 % in all the study population. The most common adverse effect was tachyarrhythmia, constituting 7.9 % of all population. These adverse effects were mostly occurred in lymphoma patients (14 %). Nineteen (3.0 %) of all patients developed atrial fibrillation mostly on the 4th day (range of 1-9 days) after transplantation. Life-threatening events are extremely rare. These adverse effects appear to be related to the type of transplantation rather than the underlying disease. Therefore, close follow-up of patients is important during the peri-transplantation period.

A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects.

INTRODUCTION: Autosomal recessively inherited lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency was shown to be responsible for different types of inborn errors of immunity, such as common variable immunodeficiency (CVID) and autoimmune lymphoproliferative syndrome (ALPS). The aim of this study was to compare patients with LRBA-related ALPS and LRBA-related CVID, to describe their clinical and laboratory phenotypes, and to prepare an algorithm for their diagnosis and management. METHODS: Fifteen LRBA-deficient patients were identified among 31 CVID and 14 possible ALPS patients with Western blotting (WB), primary immunodeficiency disease (PIDD) gene, next-generation panel screening (NGS), and whole exome sequencing (WES). RESULTS: The median age on admission and age of diagnosis were 7 years (0.3-16.5) and 11 years (5-44), respectively. Splenomegaly was seen in 93.3% (14/15) of the patients on admission. Splenectomy was performed to 1/5. Recurrent upper respiratory tract infections (93.3% (14/15)), autoimmune cytopenia (80% (12/15)), chronic diarrhea (53.3% (8/15)), lower respiratory tract infections (53.3% (8/15)), lymphoma (26.6% (4/15)), Evans syndrome (26.6% (4/15)), and autoimmune thyroiditis (20% (3/15)) were common clinical findings and diseases. Lymphopenia (5/15), intermittant neutropenia (4/15), eosinophilia (4/15), and progressive hypogammaglobulinemia are recorded in given number of patients. Double negative T cells (TCRαß+CD4-CD8-) were increased in 80% (8/10) of the patients. B cell percentage/numbers were low in 60% (9/15) of the patients on admission. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Thelper (Th) cells, markedly increased effector memory/effector memory RA+ (TEMRA) Th were documented. Large PD1+ population, increased memory, and enlarged follicular helper T cell population in the CD4+ T cell compartment was seen in one of the patients. Most of the deleterious missense mutations were located in the DUF1088 and BEACH domains. Interestingly, one of the two siblings with the same homozygous LRBA defect did not have any clinical symptom. Hematopoietic stem cell transplantation (HSCT) was performed to 7/15 (46.6%) of the patients. Transplanted patients are alive and well after a median of 2 years (1-3). In total, one patient died from sepsis during adulthood before HSCT. CONCLUSION: Patients with LRBA deficiency may initially be diagnosed as CVID or ALPS in the clinical practice. Progressive decrease in B cells as well as IgG in ALPS-like patients and addition of IBD symptoms in the follow-up should raise the suspicion for LRBA deficiency. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Th cells, and markedly increased effector memory/effector memory RA+ Th cells (TEMRA Th) cells are important for the diagnosis of the patients in addition to clinical features. Analysis of protein by either WB or flow cytometry is required when the clinicians come across especially with missense LRBA variants of uncertain significance. High rate of malignancy shows the regulatory T cell's important role of immune surveillance. HSCT is curative and succesful in patients with HLA-matched family donor.

Impact of bone marrow plasma cells percentage on survival at diagnosis and pre-transplant period in newly diagnosed multiple myeloma: Experience of a single center from Turkey.

BACKGROUND AND AIM: The current definition of complete remission (CR) in multiple myeloma (MM) includes negative serum and urine immunofixation (IFE) tests and <5% bone marrow plasma cells (BMPCs). The aim of this study was to examine the impact of BMPC percentage on survival, at diagnosis and pre-transplant period, in newly diagnosed multiple myeloma. MATERIALS AND METHODS: One hundred and fourty eight patients with newly diagnosed MM who had received autologous stem cell transplantation (ASCT) in our HSCT (hematopoietic stem cell transplant) center at Hacettepe University Hospital between the years of 2008 and 2018 were evaluated retrospectively. RESULTS: The median follow-up period was 27.4 months (range, 4.5-122) for the entire group. The 3-year OS was 87% in the pre-transplant BMPCs <5% group and 92% in the pre-transplant BMPCs ≥ 5% group, there was no statistically significant difference. The 5-year OS for the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 73% and 70%, respectively (p = 0.50). The 3-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 77% and 57%. The 5-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 43% and 13%, respectively. There was a statistically significant difference between the two groups with respect to PFS (p = 0.04). CONCLUSION: In conclusion, this study highlights the importance of reaching <5% BMPCs at pre-transplant period. OS and PFS were better in patients who had pre-transplant BMPCs <5% than pre-transplant BMPCs ≥ 5%.

Current perspectives for the treatment of chronic myeloid leukemia

With an annual incidence of 1-2 in a million, Ph*(+) chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disease that makes myeloid neoplastic cells breed out of control. This BCR-ABL(+) myeloproliferative disease makes up about 15%-20% of all leukemia cases in adults. CML is seen more in males than females, with a rate of three to two. However, it does not show differences in prevalence in terms of age. CML consists of three clinical phases. The first one is the chronic phase, defined by rising white blood cell levels and also by myeloid proliferation and bone marrow maturation. While this phase does not exhibit complications, in diagnosis, it comprises most of the patients. The second phase is the accelerated phase, which the disease progresses to if it is not treated or does not respond to treatment. This usually takes about 3 years. The third phase is the blastic phase. The chronic phase can still progress to the next two phases within the first 2 years, with a rate of 10%. In the following years, the possibility increases by 15%-20% each year. Tyrosine kinase inhibitors (TKIs) are revolutionary drugs for the management of disease course in CML. The aim of this review is to assess current approaches to CML patients' follow-up and treatment with TKIs. A literature search on CML and TKIs was made in PubMed, Web of Science, and Scopus with particular focus on randomized clinical trials, recommendations, guidelines, and expert opinions. In managing CML, various treatment methods have been utilized for many decades. Prior to the development of TKIs, interferon alpha was the primary tool, which was then complemented by allogeneic hematopoietic stem cell transplantation (HSCT). HSCT was successful in slowing the disease down in the long term and curing up to 50% of patients. Then the coming of the imatinib era opened up different treatment perspectives. For the patients resistant or intolerant to imatinib, second- and third-generation TKIs are successfully used in distinct CML disease states. The survival benefits of TKIs including imatinib, nilotinib, dasatinib, bosutinib, and ponatinib for CML patients are outstanding. TKI-related adverse events could impact the clinical course, especially in long-term drug administrations. The current aim for CML disease management in the TKI era is to provide age- and sex-matched normal life duration to CML patients.

Unclassifiable non-CML classical myeloproliferative diseases with microcytosis: findings indicating diagnosis of polycythemia vera masked by iron deficiency

Background/aim: Polycythemia Vera (PV) is a myeloproliferative disorder characterized by overproduction of morphologically normal red blood cells (RBCs), granulocytes, and platelets, a phenotype that is caused by a mutation (V617F) in Janus kinase 2 (JAK2). However, JAK2 V617F is also found in approximately 50% of patients with essential thrombocytosis and primary myelofibrosis, rendering its presence nonspecific as a diagnostic test. An increased red cell mass is a major criterion for the diagnosis of PV according to World Health Organization (WHO) 2016 criteria. High hemoglobin (Hgb) or Hematocrit (Hct) are universally used as indicators of an increased red cell mass for the diagnosis of PV. However, conditions such as iron deficiency (ID) with decreased mean cell volume may mask the diagnosis due to nonelevated Hct level. The aim of this study was to investigate the clinical characteristics of the patients with unclassifiable non-CML classical myeloproliferative disease with microcytosis (MPD/M) and nonelevated Hgb and Hct levels at diagnosis and to determine if some of these cases could be real PV cases masked due to ID-related microcytosis. Materials and methods: There were 23 MPD/M cases among 208 non-CML classical MPD cases (11%). Among 22 patients who had adequate test results related to the cause of microcytosis, ID and beta-thalassemia trait (TT) were the apparent causes of microcytosis in 15 and 1 cases, respectively. Results: Clinicopathological correlations revealed consistently positive JAK2 V617F mutation status (20/20, 100%), frequently elevated RBC count (17/23, 73.9%), and PV-compatible bone marrow findings (10/12, 83.3%). These findings are compatible with PV instead of essential thrombocytopenia or primary myelofibrosis. In spite of frequent cytoreductive treatment, 3 patients developed increased Hgb/Htc levels during median 58.2 (279­63) months' follow-up. Conclusion: These data show that the majority of MPD/M cases are PV patients masked due to ID-related microcytosis.

Mitoxantrone-melphalan conditioning regimen for autologous stem cell transplantation in relapsed/refractory lymphoma

Background/aim: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL). In this study, we report the outcome of the mitoxantrone-melphalan conditioning regimen for lymphoma. Materials and methods: The study group included 53 patients who were relapsed/refractory HL (n = 14) and NHL (n = 39) and received mitoxantrone and melphalan followed by ASCT. The transplant regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by peripheral blood stem cell infusion (PBSC). Results: Prior to high-dose chemotherapy, 37.7% of the patients were in complete remission (CR) and 45.3% were in partial remission (PR), and 17% had stable or progressive disease. After high-dose chemotherapy and PBSC, 44 out of 51 patients achieved CR (86.2%). CR was achieved in 24 out of 33 patients (72.7%) who were transplanted in a marginally active phase of the disease. At a median followup of 25.4 months (1.8­131.3 months) after ASCT, 13 patients relapsed/ progressed and 8 patients died. The estimated 2-year overall survival (OS) was 81.9%, and event-free survival (EFS) was 59.3%. Conclusion: High-dose chemotherapy followed by ASCT is an effective conditioning regimen in relapsed/refractory lymphoma patients who are undergoing ASCT.

Capecitabine-induced coronary artery vasospasm in a patient who previously experienced a similar episode with fluorouracil therapy.

Capecitabine is a chemotherapeutic agent used in the treatment of metastatic colon cancer and metastatic breast cancer. It is metabolized into fluorouracil (5-FU) in the liver; hence, its mechanism of action is similar to that of 5-FU. Cardiac toxicity, although rarely seen, may be of concern in some patients. Although multiple hypotheses have been proposed for the mechanism of cardiotoxicity, coronary vasospasm is the most commonly accepted one, as patients usually present with chest pain resembling acute myocardial infarction. Electrocardiography may demonstrate ST-segment elevation, and cardiac biomarkers may be elevated. Cardiotoxicity with 5-FU has been reported widely. Capecitabine has been shown to be much less cardiotoxic compared to 5-FU, with only a handful of cases reporting cardiotoxicity with capecitabine. There are no cases reporting cardiotoxicity with both 5-FU and capecitabine in the same patient. In this case report, we present a patient with adverse cardiac effect with capecitabine whose previous 5-FU therapy was stopped due to cardiotoxicity.

Assessment of cardiac autonomic nervous system involvement in systemic sclerosis via exercise heart rate recovery.

OBJECTIVE: To assess exercise heart rate recovery (HRR) indices in patients with systemic sclerosis (SSc) for an assessment of their cardiac autonomic function. SUBJECTS AND METHODS: Thirty-five patients with diffuse or limited SSc and 35 healthy controls were enrolled. All subjects underwent exercise testing and transthoracic echocardiography. The HRR indices were calculated by subtracting the first- (HRR1), second- (HRR2) and third-minute (HRR3) heart rates from the maximal heart rate. RESULTS: The SSc and control groups were similar in age (45.2 ± 11.6 vs. 43.9 ± 10.0 years), had identical gender ratios (31 female/4 male in both groups) and similar left ventricular ejection fraction (66.5 ± 5.1 vs. 67.7 ± 5.9%). The mean HRR1 (21.8 ± 4.4 vs. 27.7 ± 4.3 bpm, p = 0.001), HRR2 (43.8 ± 6.3 vs. 47.6 ± 4.4 bpm, p = 0.004) and HRR3 (58.8 ± 10.3 vs. 63.6 ± 7.3 bpm, p = 0.031) values were significantly lower in the SSc group than in the healthy controls. HRR indices were similar in the limited and diffuse SSc subgroups. CONCLUSIONS: The patients with SSc had lower HRR indices than normal subjects. Cardiac autonomic functions might be involved in SSc, even in patients without cardiac symptoms.

Four­Dimensional Echocardiographic Evaluation of Cardiac Iron Overload in Patients with Beta-Thalassemia Major.

Cardiac magnetic resonance imaging is the gold standard to detect cardiac iron overload in patients with beta-thalassemia. The aim of this study was to evaluate cardiac iron overload using four-dimensional transthoracic echocardiography in thalassemia patients with and without cardiac involvement detected by T2* value and to compare the two techniques. This cross-sectional and observational study was conducted in 44 patients diagnosed with thalassemia major. Left ventricular systolic function was assessed using four-dimensional speckle tracking echocardiography-derived global longitudinal (GLS), circumferential, radial, and area strain indices. Left ventricular ejection fraction, volumes, and mass index were similar between the patients with T2* values less than 20 ms as compared to those with T2* values greater than 20 ms. However, patients with lower T2* values had significantly higher GLS values (- 17.0% vs. - 19.8%, p < 0.001) compared with those with higher T2* values. GLS demonstrated a sensitivity of 91.7% and a specificity of 71.9% at a cut-off value of - 18.5%; however, sensitivity was 75%, and the specificity was 84.4% at a cut-off value of - 17.5%. For - 18.5%, the positive predictive value was 55%, and the negative predictive value was 95.8%; for - 17.5%, these values were 64.2 and 90%, respectively. This novel echocardiographic method, tested for the first time in our study in comparison with cardiac MRI in an adult patient group, has been shown to predict cardiac iron overload in thalassemia patients in the subclinical period without LVEF decline. Four-dimensional GLS is a marker with high sensitivity and negative predictive value.

Downregulation of Stearoyl-CoA Desaturase 1 (SCD-1) Promotes Resistance to Imatinib in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance.

Comparison of Risk Scoring Systems in HLA-Matched Related Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Objective: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a potentially curative treatment of choice for many hematological diseases. However, there are some transplantation-related risks. Predicting the risk-benefit ratio prior to AHSCT facilitates the choice of conditioning regimens and posttransplant follow-up. Hence, many risk models have been developed. The aim of the present study was to compare 6 different risk models that are clinically used. Materials and Methods: A total of 259 patients were enrolled in this study. The European Society for Blood and Marrow Transplantation (EBMT), Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), Age-Adjusted Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI-Age), revised Pretransplant Assessment of Mortality (rPAM), Acute Leukemia-EBMT (AL-EBMT), and Disease Risk Index (DRI) risk models were applied retrospectively. Results: The AL-EBMT, HCT-CI, and HCT-CI-Age scoring systems were found to be predictive for 2-year overall survival (OS) and 2-year non-relapse mortality (NRM) (2-year OS: AL-EBMT, reference vs. score 8.5-10, HR: 1.3, p=0.035; AL-EBMT, reference vs. score >10, HR: 3.8, p=0.001; HCT-CI: reference vs. score 1-2, HR: 1.4, p=0.018; HCT-CI: reference vs. score ≥3, HR: 2.5, p<0.001; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p<0.001; HCT-CI-Age: reference vs. score ≥3, HR: 3.2, p<0.001) (2-year NRM: AL-EBMT: reference vs. score 8.5-10, HR: 1.61, p<0.001; AL-EBMT: reference vs. score >10, HR: 3.3, p<0.001; HCT-CI: reference vs. score 1-2, HR: 1.3, p=0.028; HCT-CI: reference vs. score ≥3, HR: 2.3, p=0.011; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p=0.01; HCT-CI-Age: reference vs. score ≥3, HR: 2.4, p=0.003). In terms of the Kaplan-Meier estimates of 2-year OS and 2-year NRM, the risk scoring system with the highest predictive power was found to be AL-EBMT (2-year AUC: 0.59 and 0.60, respectively). The other scores were not found to be predictive for 2-year OS and NRM. Conclusion: In the present study at our bone marrow and stem cell transplant center, it has been demonstrated that the HCT-CI, HCT-CI-Age, and AL-EBMT are good predictors of 2-year NRM and OS.

Effect of Salvage Chemotherapy Before Donor Lymphocyte Infusion in Patients With Relapse After Allogeneic Hematologic Stem Cell Transplantation.

OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (AHSCT) is an important treatment option in hematologic malignancies. Relapse after AHSCT is an indicator of poor prognosis. These patients may be treated with donor lymphocyte infusion (DLI). The chemotherapy given before DLI increases the success of the treatment by reducing the burden of disease. The aim of this study is to investigate post-DLI graft vs host disease (GvHD) and survival based on the course of chemotherapy given before DLI. METHODS: A total of 23 patients who received DLI because of relapsed disease after AHSCT were enrolled. All of the patients received 1 or more courses of cytoreductive chemotherapy before DLI. RESULTS: Complete remission (CR) after DLI remained in 78.2% of all patients. There is no difference between 1 or multiple courses of chemotherapy in terms of CR (55.6% vs 44.4%; P = .21). During follow-up after DLI, although it did not reach statistical significance (P = .09), the patients receiving single-course chemotherapy tended to have longer survival (36.1 vs 4.3 months, respectively). Four patients who received multiple courses of chemotherapy were lost because of infection-related disease (pneumonia, sepsis) while they were in CR. GvHD development was more frequent in patients receiving multiple courses of chemotherapies (60% of all GvHD patients). CONCLUSION: It has been demonstrated that reducing the tumor burden by multiple-cycle chemotherapy does not have any advantage in terms of CR and does not improve the overall survival.

Comparison of single and double autologous stem cell transplantation in multiple myeloma patients.

BACKGROUND: Autologous stem cell transplantation (ASCT) is one of the standard treatments of choice for eligible multiple myeloma (MM) patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients. MATERIALS AND METHODS: Patients who were diagnosed as having MM and had undergone single or double ASCT in our clinic between the years 2003 and 2020 were retrospectively examined. RESULTS: In this study, the median time of second ASCT is approximately 3.6 years from the first ASCT. Overall survival (OS) duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively (p: 0.33). Progression-free survival (PFS) duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively (p: 0.22). Disease assessment after ASCT stable or progressive disease, partial remission, and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively (p: 0.22). CONCLUSION: The present study points out that the second ASCT treatment option for MM patients may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.

Allogeneic Hematopoietic Stem-Cell Transplantation Improves Disease-Free Survival Compared to Pediatric-Inspired Berlin-Frankfurt-Münster Chemotherapy in Adult Acute Lymphoblastic Leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a malign disease with poor prognosis in adults. After remission is achieved by induction therapy, administration of allogeneic hematopoietic stem-cell transplantation (AHSCT) is one of the standard treatment in adult ALL patients. Pediatric-inspired chemotherapy has been demonstrated to improve outcomes of adult ALL. The aim of this study was to compare the Berlin-Frankfurt-Münster-95 chemotherapy (BFM-95) regimen and AHSCT results in ALL patients with first complete remission. PATIENTS AND METHODS: Forty-seven patients who received the BFM-95 regimen and 83 patients who underwent AHSCT were compared. Primary endpoints were comparison of overall survival (OS) and disease-free survival (DFS) between groups. RESULTS: There was no significant difference between the groups in terms of age, gender, or performance status. In BFM-95 and AHSCT, relapsed disease occurred in 11 (23.4%) and 24 (28.9%), respectively; the respective values for treatment-related mortality were 6 (12.7%) and 10 (12%) (P = .32 and .91). Five-year DFS was 38% with BFM-95 and 57% with AHSCT (P = .014). There was no 5-year OS difference in both groups (64% vs 60%, P = .13). While leukocyte count < 30 × 109/L at the time of diagnosis (hazard ratio, 2.7; P = .021) and prophylaxis of central nervous system (hazard ratio, 2; P = .036) were prognostic for OS, the only factor that had a prognostic effect on DFS was AHSCT (hazard ratio, 1.6; P = .041). CONCLUSION: AHSCT currently offers no special OS advantage but increases DFS compared to the BFM-95 regimen. AHSCT may be considered at first complete remission in patients at low risk of transplant-related mortality.

Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. RESULTS: The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. CONCLUSION: Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.