Synthesis of novel indol-3-acetamido analogues as potent anticancer agents, biological evaluation and molecular modeling studies.

Cannabinoids bind to cannabinoid receptors CB1 and CB2 and their antitumoral activity has been reported against some various cancer cell lines. Some synthetic cannabinoids possessing indole rings such as JWH-015 and JWH-133 particularly bind to the cannabinoid CB2 receptor and it was reported that they inhibit the proliferation and growth of various cancer cells without their psychoactive effects. However, the pharmacological action mechanisms of the cannabinoids are completely unknown. In this study, we report the synthesis of some new cannabinoidic novel indoles and evaluate their anticancer activity on various cancerous and normal cell lines (U87, RPMI 8226, HL60 and L929) using several cellular and molecular assays including MTT assay, real-time q-PCR, scratch assay, DAPI assay, Annexin V-PE/7AAD staining, caspase3/7 activity tests. Our findings indicated that compounds 7, 10, 13, 16, and 17 could reduce cell viability effectively. Compound 17 markedly increased proapoptotic genes (BAX, BAD, and BIM), tumor suppressor gene (p53) expression levels as well as the BAX/BCL-2 ratio in U87 cells. In addition, 17 inhibited cell migration. Based on these results, 17 was chosen for determining the mechanism of cell death in U87 cells. DAPI and Annexin V-7AAD staining results showed that 17 induced apoptosis, moreover activated caspase 3/7 significantly. Hence, compound 17, was selected as a lead compound for further pharmacomodulation. To rationalize the observed biological activities of 17, our study also included a comprehensive analysis using molecular docking and MD simulations. This integrative approach revealed that 17 fits tightly into the active site of the CB2 receptor and is involved in key interactions that may be responsible for its anti-proliferative effects.

Synthesis of some new 2-(substituted-phenyl)imidazo[4,5-c] and [4,5-b]pyridine derivatives and their antimicrobial activities.

The synthesis of 5H-imidazo[4,5-c]pyridines analogues (1a - 1h) and 4H-imidazo[4,5-b]pyridines (3a - 3c) was achieved by reacting 3,4-diaminopyridine or 2,3-diaminopyridine with Na2S2O5 adduct of corresponding benzaldehydes (a1 - a8). Alkylation of compounds (1a - 1h) and (3a - 3c) using 4-chlorobenzyl and /or butyl bromide under basic conditions (K2CO3, DMF) predominantly resulted in the formation of N5 regioisomers (2a - 2l) and N4,3 regioisomers (4a - 4c1,2), respectively. The N5,4,3-regioisomeric structures were confirmed using 2D-NOESY (Nuclear Overhauser Effect Spectroscopy) and HMBC (Heteronuclear Multiple Bond Correlation) spectra. The antibacterial and antifungal activities of the synthesized compounds (2a - 2g, 4a - 5d) were evaluated in vitro against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin resistant S. aureus, Enterococcus faecalis and Candida albicans, Candida parapsilosis. Among the synthesized compounds, promising activities were observed with compounds 2g, 2h, 4a and 4b with lowest MIC values (4-8 µg/mL). The compounds 2i, 2j, 2k, 2l showed moderate activity. Additionally, a computational approach (ADMETlab 2.0) was used to evaluate the drug likeness properties of the compounds.

A single-center experience of haploidentical stem cell transplantation in hematological malignancies.

BACKGROUND: Since well-designed prospective comparative trials are lacking, haploidentical hematopoietic stem cell transplantations approach should be based on the expertise of a particular center. In this study, we aimed to report the results and outcomes of patients who underwent haploidentical hematopoietic stem cell transplantation. METHODS: : Thirty-nine patients who underwent transplantation in our clinic between 2015 and 2022 were retrospectively analyzed. Primary end point of this study is to find out the survival rates of the patients. RESULTS: The overall survival of patients was 29.9 ± 4.9 months. The disease-free survival of the patients was 37.8 ± 5.7 months. The 3-year overall survival rate of the patients was %50 and the 3-year disease-free survival rate of the patients was %53. Nineteen patients were nonsurvivors among a total of 39 patients. Busulfan-fludarabine-thiotepa was the most frequently used conditioning regimen for transplantation. Busulfan-fludarabin-antithymocyte globulin regimen is the second preferred conditioning regimen. Cyclosporine- cyclophosphamide-mycophenolate mofetil was the most widely used graft-versus-host disease prophylaxis regimen. Sixteen patients had graft-versus-host disease, 28% of the patients had acute graft-versus-host disease, and 13% had chronic graft-versus-host disease. Gastrointestinal system consists of the most involved organs in graft-versus-host disease since 15% of the patients had gastrointestinal graft-versus-host disease. First-degree relatives (parent/child) were the most frequent donor source for haploidentical hematopoietic stem cell transplantation. Sepsis was the most frequent reason of death among transplant patients. DISCUSSION: In our center, we prefer to use high dose posttransplantation cyclophosphamide after haploidentical hematopoietic stem cell transplantation for graft-versus-host disease prophylaxis. With this approach, our center's overall survival and disease-free survival rates are comparable and compatible with the literature findings.

Hypophosphatemia related to the use of ibrutinib.

INTRODUCTION: Tyrosine kinase inhibitors (TKis) and Bruton's TKi (BTKis) constitute broadly used antitumor drug groups with almost completely tolerable and manageable side-effect profiles. Mainly side effects are cardiovascular and gastrointestinal for the TKi group. Hypophosphatemia is documented frequently in many studies with TKis but rarely mentioned with ibrutinib use up to the present. CASE REPORT: A 61-year-old patient with the diagnosis of chronic lymphocytic leukemia had hypophosphatemia-related complaints and symptoms when ibrutinib use was preferred for his second relapse of the disease. After drug discontinuation, we started ibrutinib again with an alternating dose. We managed to control hypophosphatemia, and the patient has been following up for 2 years in remission status without any support or a second drug need. MANAGEMENT AND OUTCOME: We have presented here a chronic lymphocytic leukemia case that developed mild-severe hypophosphatemia associated with ibrutinib use. By using an alternating dose of ibrutinib, we managed to control the disease and drug side effects. DISCUSSION: TKis and BTKis are widely in use for different indications. Hypophosphatemia is rare but it can cause drug discontinuation or change if it is not manageable. It is mentioned that hypophosphatemia can be seen due to a common group effect with the mechanism of causing secondary hyperparathyroidism and renal tubulopathy. In our case, we could explain the side effect of hypophosphatemia with secondary hyperparathyroidism and renal tubulopathy. Prospective, large-group studies are needed to explain the hypophosphatemia and other side effects of ibrutinib and new BTKis in detail.

Asymptomatic unilateral phrenic nerve palsy after bortezomib treatment in a newly diagnosed multiple myeloma patient.

INTRODUCTION: Bortezomib is the first chemotherapeutic agent of proteosome inhibitor class that can be used in newly diagnosed and relapsed/refractory multiple myeloma. It is well known that bortezomib has side effects such as peripheral sensory, motor, or autonomic neuropathy. In this paper, we will present our patient who developed unilateral phrenic nerve palsy as an autonomic neuropathy after six cycles of subcutaneous bortezomib treatment. This case differs from other cases in that our patient was asymptomatic. CASE REPORT: A 57-year-old male patient was admitted with back pain and gait disturbances. In the thorax computed tomography, a soft tissue mass causing compression on the spinal canal was observed in the T12 vertebra. Bone biopsy pathology report resulted in diffuse plasma cell infiltration. The patient was diagnosed with stage ISS-3, IgG kappa type multiple myeloma. MANAGEMENT AND OUTCOME: Subcutaneous bortezomib 1 × 2.2 mg (Days 1-4-8-11) + intravenous cyclophosphamide 1000 mg (Day 1) + intravenous dexamethasone 40 mg (Days 1-2-3-4) (VCD chemotherapy protocol) was started. Totally six cycles of VCD were administered. While the patient did not have any respiratory symptoms, an elevation consistent with phrenic nerve palsy was observed in the left hemidiaphragm in the thorax computed tomography that was taken during the preparation for autologous hematopoietic stem cell transplantation. DISCUSSION: Bortezomib is a frequently used chemotherapeutic agent in patients with multiple myeloma and care should be taken in terms of the risk of developing phrenic nerve palsy in patients. There are cases of autonomic neuropathy developing after bortezomib treatment.

Comment on Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874.

The SARS-CoV-2 spike protein mRNA-based vaccines have prevented countless mortality and morbidity, and have an excellent risk/benefit ratio. However, various adverse events may rarely occur after the BNT162b2 vaccine, like any other medical intervention. The COVID-19 itself and the spike protein produced endogenously by mRNA vaccines may have immunological, microenvironmental, prothrombotic, and neoplastic effects. As a contribution to the published report, we would like to share our experience regarding four cases in which myeloid neoplasms emerged following the vaccination. Conclusions: There is no doubt that vaccination could continue along the lines of established universal recommendations. Meanwhile, all hematological adverse events must be closely monitored and reported. Further efforts should be focused on the probable pathobiological mechanisms and causalities of spike protein-related toxicity and clonal myeloid disorders.

Efficacy of eltrombopag in thrombocytopenia after hematopoietic stem celltransplantation.

BACKGROUND: Thrombocytopenia is a common complication following hematopoietic stem cell transplantation (HSCT). Eltrombopag has been used in thrombocytopenia treatment after HSCT in recent years. Herein, we present our experience of 25 patients treated with eltrombopag for post-HSCT thrombocytopenia. METHODS: Fifteen autologous hematopoietic stem cell transplantation (AHSCT) and 10 allogenic hematopoietic stem cell transplantation (allo-HSCT) recipients treated with eltrombopag for treatment of prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) in the stem cell transplantation unit of Hacettepe University Hematology Department between 2017 and 2021 were included in the study. The primary endpoint of this study is eltrombopag response in patients diagnosed with PIT or SFPR. Platelet count above 50,000/mm3 for five consecutive days without platelet transfusion was considered as eltrombopag response. Overall survival (OS) analyses were calculated based on the time between HSCT and death from any cause. The patients who were alive at the last follow-up were censored at this time for calculation of OS analyses. RESULTS: AHSCT (66.7% (10/15)) and allo-HSCT (50% (5/10)) recipients responded to eltrombopag for the treatment of post-HSCT thrombocytopenia. There was no excess toxicity related to the eltrombopag use. The median response duration of allo-HSCT recipients and AHSCT recipients were 41 (13-104) days and 50 (7-342) days, respectively. There was a statistically significant OS duration difference between the responders and nonresponders in allo-HSCT and AHSCT recipients with p values of 0.005 and 0.02, respectively. DISCUSSION: Eltrombopag is promising for the treatment of thrombocytopenia after AHSCT and allo-HSCT in terms of efficacy and safety.

Hepatitis E Virus Prevalence and Associated Risk Factors in High-Risk Groups: A Cross-Sectional Study.

BACKGROUND: Seroepidemiology, risk factors to hepatitis E virus exposure, and prevalence of hepatitis E virus viremia have not yet been investigated among patients under immunosuppression or with liver disease that are high risk for infection in Turkey. METHODS: In this cross-sectional study, 292 consecutive serum samples from renal transplant recipients, allogeneic hematopoietic stem cell transplant recipients, patients with acute hepatitis, and patients with chronic hepatitis C were prospectively collected in a ter- tiary university hospital. Sera were tested for hepatitis E virus immunoglobulin G/immunoglobulin M and hepatitis E virus ribonucleic acid using commercial enzyme-linked immunosorbent assay and in-house nested polymerase chain reaction with Sanger sequencing, respectively. Sociodemographic, clinical, laboratory data, and risk factors were collected using a questionnaire and hospital database. Multiple logistic regression analysis was employed to identify independent predictors for anti-hepatitis E virus seropositivity. RESULTS: Among all patients, only 2 patients (1 renal transplant recipient and 1 patient with acute hepatitis) were identified as having hepatitis E virus genotype 3 viremia. Hepatitis E virus viremia rate was 0.6% in whole group. These patients showed no signs of chronic hepatitis E virus infection for 6 months and were spontaneously seroconverted 6 months after enrollment. Anti-hepatitis E virus IgG was positive in 29 patients yielding a hepatitis E virus seroprevalence of 9.9%. Older age (adjusted odds ratio: 1.03, 95% CI, 1.00-1.06; P = .022) and eating undercooked meat (adjusted odds ratio: 3.11, 95% CI, 1.08-8.92; P = .034) were independent risk factors to anti- hepatitis E virus seropositivity in all patients. Similarly, multiple logistic regression analysis demonstrated that age (adjusted odds ratio: 1.03, 95% CI, 0.99-1.07, P = .058) and eating undercooked meat (adjusted odds ratio: 5.77, 95% CI, 1.49-22.25, P = .011) were indepen- dent risk factors for anti-hepatitis E virus IgG positivity in the liver disease subgroup consisting of acute hepatitis and chronic hepatitis C patients. CONCLUSION: The hepatitis E virus seroprevalence rate was high (9.9%), despite low viremia rate (0.6%) in high-risk patients. The emer- gence of hepatitis E virus genotype 3 might indicate a serious problem for these patients. Future investigations are needed to elucidate foodborne transmission routes of hepatitis E virus in Turkey.

Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microanjiopathy (TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter study aimed to define the distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as having acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 80 patients (women: 50; man: 30) with a median age of 48 (20-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 29 (36.2 %), 22 (27.5 %), 23 (28.8 %) and 6 (7.5 %) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

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.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microangiopathy(TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter (n:18) study aimed to define distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for a presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 97 patients (female: 60; male: 30) with a median age of 48 (18-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 32 (33 %), 33 (34 %), 26 (27 %) and 6 (6%) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

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.

Synthesis, in vitro antiprotozoal activity, molecular docking and molecular dynamics studies of some new monocationic guanidinobenzimidazoles.

A series of monocationic new guanidinobenzimidazole derivatives were prepared in a four step process starting from 2-nitro-1,4-phenylendiamine. Their antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani were evaluated in vitro. Two out of 20 tested monocationic compounds (7, 14) showed close activity with reference drug chloroquine against P. Falciparum. To understand the interactions between DNA minor groove and in vitro active compounds (7, 14) molecular docking studies were carried out. Stability and binding energies of DNA-ligand complexes formed by DNA with compounds 7 and 14 were measured by molecular dynamics simulations throughout 200 ns time. Root mean square deviation (RMSD) values of the ligands remained stable below 0.25 mm and root mean square fluctuation (RMSF) values of the active site residues with which it interacted decreased compared to the apo form. All compounds exhibited theoretical absorption, distribution, metabolism and excretion (ADME) profiles conforming to Lipinski's and Ghose's restrictive rules.

Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia: A Multicenter Turkish Experience

Objective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without. Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed. Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs). Conclusion: Allogeneic HCT with MSDs or MUDs is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.

Central nervous system involvement in patients with acute myeloid leukemia

Background/aim: To evaluate the incidence, clinical features, risk factors, and prognosis of central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML). Materials and methods: All AML patients who were admitted to Hacettepe University hospital between 2000 and 2021 were evaluated. The medical records of 548 AML cases were retrospectively analyzed. Results: The frequency of CNS involvement was 2.4% (n = 13) at diagnosis and 4.6% (n = 25) at diagnosis or during follow-up. Parenchymal involvement was seen in 5 patients, leptomeningeal involvement was seen in 11 patients. Three patients had both leptomeningeal and parenchymal involvements, and 6 patients had optic nerve or ocular involvement. In univariate analysis, younger age and extramedullary involvement at diagnosis were associated with CNS disease at diagnosis, and extramedullary involvement at diagnosis was associated with CNS disease during follow-up. In multivariate analysis; younger age and extramedullary involvement at diagnosis were associated with CNS disease at diagnosis and during follow-up respectively. Median overall survival was 5.4 months in patients with CNS disease at diagnosis and 16.9 months in patients with CNS disease during follow-up and 16.2 months in patients with no CNS disease. Conclusion: CNS disease is a rare complication of AML. Younger age and extramedullary involvement at diagnosis are risk factors for CNS involvement.

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.

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.