Multicentral Retrospective Analysis of Venetoclax-Based Treatments in AML and MDS: A Real-World Study by the Turkish Hematology Network Group.

Background and Objectives: Acute myeloid leukemia and myelodysplastic syndrome are both clonal hematologic malignancies that primarily affect older adults. Current treatments for AML/MDS are both limited in number and efficacy. This study aims to evaluate venetoclax-based therapies in AML/MDS, focusing on overall survival and recurrence-free survival rates, and to expand real-world data on its use. Materials and Methods: Clinical and laboratory data on patients with AML/MDS aged 18≥ treated with venetoclax between January 2019 and July 2022 were included. Survival analysis was calculated based on the period from 2019 to December 2023. Results: A total of 161 AML and 40 patients with MDS were included. The median age was 63.53 ± 15.30 years for AML and 70.12 ± 10.21 years for MDS. In both groups, over 55% are male. A total of 77.6% of patients with AML and 75% of patients with MDS received treatment prior to venetoclax. Venetoclax was administered in combination with azacitidine to 84.5% of AML and 67.5% of MDS. The relapse rate in AML is approximately 15%. Overall, the 2-year survival rate is 46% and 18.73 months. The overall CR/CRi rate for patients with AML is 49.1%, while for patients with MDS, it is 50%. The 2-year survival rate for patients with MDS is 52.7%. The 2-year RFS rate was 75.5% for AML and 90.9% for MDS. The relapse rate in AML is approximately 15%. The percentage of adverse events leading to treatment discontinuation among those with grade 3-4 toxicity is low; 26.7% for AML (n = 43) and 15% for MDS (n = 6). Conclusions: Our real-world data demonstrate that venetoclax has the potential to improve overall survival rates when used in combination with HMAs and supports its use in patients with AML/MDS.

Therapeutic plasma exchange in critically ill children: 18-year experience of a tertiary care paediatric intensive care unit.

BACKGROUND: Therapeutic plasma exchange (TPE) has been used as a primary or supportive treatment in critical paediatric patients during the clinical course of many diseases. OBJECTIVES: The objective of this study was to characterise the indications, complications, and outcomes of critically ill children who received TPE in a tertiary referral paediatric intensive care unit (PICU). METHODS: This retrospective observational study was conducted in a tertiary referral 13-bed PICU of a university hospital. Critically ill children, who received at least one TPE procedure, were retrospectively included in the study. TPE was utilised by the same paediatric intensivist in accordance with the American Society for Apheresis (ASFA) guideline between January 2005 and December 2022. The procedures were analysed in terms of technical aspects and complications. Multivariable logistic regression analysis was performed to identify independent risk factors for mortality. RESULTS: In total, 1528 TPE sessions were performed on a total of 328 children. The overall TPE utility rate was 25 per 1000 PICU admissions. Primary indications for TPE were sepsis, neurological autoimmune, haematological diseases, acute liver failure, drug overdose, and autoimmune rheumatological disorders in 109 (33.2%), 90 (27.4%), 49 (14.9%), 43 (13.1%), 12 (3.7%), and 10 (3%) of patients, respectively. The distribution of TPE indications according to ASFA categories was as follows: 37 patients (11.3%) were in category I, 44 patients (13.4%) were in category II, and 211 (64.3%) were in category III. Complications were observed in 18.7% of sessions, and the most common complications were haemodynamic (10.8%) and circuit-/catheter-related (7.6%) complications. The mortality rate was 28.4% in the study. Moreover, both Pediatric Index of Mortality 3 score and number of organ failures were found as independent risk factors for mortality. CONCLUSIONS: Our results revealed that TPE may be an effective procedure even in critically ill children in accordance with ASFA recommendations. We also showed that mortality rate increased with Pediatric Index of Mortality 3 score at admission and number of organ failures.

Efficacy of Bendamustine, Pomalidomide, and Dexamethasone (BPD) Regimen in Relapsed/Refractory Extramedullary Myeloma: A Retrospective Single-Centre Study, Real-Life Experience.

BACKGROUND AND OBJECTIVES: Relapsed/refractory extramedullary myeloma (RREMM) is an uncommon and aggressive subtype of multiple myeloma defined by plasma cell proliferation outside the bone marrow. Therapeutic options for RREMM are limited, and the prognosis is generally unfavorable. This research aimed to assess the effectiveness of the bendamustine, pomalidomide, and dexamethasone (BPD) regimen in patients with RREMM. MATERIAL AND METHODS: We carried out a retrospective investigation of 11 RREMM patients who underwent BPD treatment. The primary endpoint was progression-free survival. The secondary endpoints of the study were two-year survival and overall response rate (ORR). We analyzed the sociodemographic and clinical features of the patients. RESULTS: The average age of the patients was 62 years. They had a median of four prior treatment lines, and eight patients had previously received autologous stem-cell transplantation. After eight BPD treatment cycles, the ORR stood at 54%, with one very good partial response (VGPR), five partial responses (PR), three progressive diseases (PD), and two stable diseases (SD). The median follow-up was 15 months, with a two-year PFS rate of 71.3% and a two-year survival rate of 81.8%. CONCLUSIONS: The BPD regimen demonstrated promising effectiveness in RREMM patients, yielding favorable ORR and survival rates. To corroborate these findings and explore additional treatment alternatives for this patient group, larger prospective studies are required.

The Use of Gemtuzumab Ozogamicin as Salvage Therapy in Patients with Acute Myeloid Leukemia: A Monocentric Real-World Experience.

Background and Objectives: Relapsed or refractory acute myeloid leukemia (r/r AML) is a disease with a poor prognosis. Limited treatment options are available in r/r AML. Here, we administered gemtuzumab ozogamicin (GO) as salvage therapy in twenty-four patients with r/r AML. The aim of the study was to determine the role of GO in r/r AML in real life. Material and Methods: This retrospective observational study recruited 24 adult patients with diagnosed r/r AML from 2018 to 2022. Twenty-four patients with r/r AML were treated with GO. GO treatment was used as monotherapy in 23 patients and in combination with cytarabine in 1 patient. At the time of diagnosis, the risk status of all patients was determined as favorable, intermediate, or adverse according to the 2017 ELN AML guidelines. Results: The median follow-up was 44.3 (13-144) months. Fifteen (62.5%) of the twenty-four patients were in the intermediate-risk cytogenetics group and nine (37.5%) were in the favorable cytogenetics group. The most common adverse events included nausea/vomiting in 79.17% (n = 19) of patients, headache in 62.50% (n = 15), elevated LFTs in 37.50% (n = 9), febrile neutropenia in 25% (n = 6), and bleeding in 25% (n = 6). The most common cause of death was infection. The most common causes of mortality were septic shock, accounting for 33.3% (n = 8) of deaths, and opportunistic lung infection, accounting for 12.5% (n = 3) of deaths. Acute infusion-related toxicities associated with GO were usually transient and, in most cases, responded to the standard of care treatment. After treatment with GO, 16.6% (n = 4) of patients achieved MLFS and 37.5% (n = 9) achieved CR. The overall response rate was 54.1%. The median overall survival time of the patients was 44 months (37.8-50.2 months). Disease-free survival was 22 months (0-48.6 months). The 5-year survival rate was 33%. Conclusions: A low dose of GO improved the overall survival and disease-free survival in r/r AML patients. GO treatment had a positive safety profile in terms of toxicity.

Long-Term Efficacy of Erythropoiesis-Stimulating Agents in Patients with Low-Risk or Intermediate-1-Risk Myelodysplastic Syndrome: Multicenter Real-Life Data

Objective: This study was undertaken to evaluate the long-term clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndrome (MDS) in a real-life setting. Materials and Methods: A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion needs were recorded before treatment and at 12 months, 24 months, 36 months, and 48 months of treatment. Results: At the 36-month (p=0.025) and 48-month (p=0.022) visits, epoetin alfa yielded significantly higher hemoglobin levels compared to darbepoetin alfa. Transfusion needs were also significantly lower with epoetin alfa compared to darbepoetin alfa at 24 months (p=0.012) and in the low-risk group compared to the intermediate-risk group at 24 months (p=0.018), 36 months (p=0.025), and 48 months (p<0.001). Treatment response rates at the 24-month, 36-month, and 48-month visits in the epoetin alfa (43.0%, 33.6%, and 27.1%), darbepoetin alfa (29.9%, 22.7%, and 16.5%), low-risk (39.3%, 30.0%, and 26.0%), and intermediate-risk (29.6%, 24.1%, and 11.1%) groups were lower than those obtained at 12 months, and the values differed significantly for the 36-month and 48-month visits with values ranging from p<0.05 to p<0.001. Conclusion: This real-life long-term ESA extension study investigated the clinical efficacy of epoetin alfa and darbepoetin alfa for up to 48 months, revealing that treatment efficacy reached a plateau starting from the 24th month of therapy with a continuing decrease in treatment response rates regardless of treatment type, risk status, or gender. Nonetheless, significantly higher hemoglobin levels and marked improvement in transfusion needs were evident in epoetin-treated patients compared to darbepoetin-treated patients and in the low-risk group compared to the intermediate-risk group.

Impact of COVID-19 on Outcomes of Patients with Hematologic Malignancies: A Multicenter, Retrospective Study.

Objectives: Patients with hematological malignancies have a high risk of mortality from coronavirus disease 2019 (COVID-19). This study aimed to investigate the impact of COVID-19 on mortality rates in patients with various hematological malignancies and to determine risk factors associated with all-cause mortality. Methods: A multicenter, observational retrospective analysis of patients with hematological malignancies infected with COVID-19 between July 2020 and December 2021 was performed. Demographic data, clinical characteristics, and laboratory parameters were recorded. Patients were grouped as non-survivors and survivors. All-cause mortality was the primary outcome of the study. Results: There were 569 patients with a median age of 59 years. Non-Hodgkin lymphoma (22.0%) and multiple myelomas (18.1%) were the two most frequent hematological malignancies. The all-cause mortality rate was 29.3%. The highest mortality rates were seen in patients with acute myeloid leukemia (44.3%), acute lymphoid leukemia (40.5%), and non-Hodgkin lymphoma (36.8%). The non-survivors were significantly older (p<0.001) and had more comorbidities (p<0.05). In addition, there were significantly more patients with low lymphocyte percentage (p<0.001), thrombocytopenia (p<0.001), and high CRP (p<0.001) in the non-survived patients. Age ≥ 65years (p=0.017), cardiac comorbidities (p=0.041), and continuation of ongoing active therapy for hematological cancer (p<0.001) were the independent risk factors for the prediction of mortality. Conclusions: In patients with hematological malignancies, coexistent COVID-19 leads to a higher mortality rate in elderly patients with more comorbidities. Acute myeloid and lymphoid leukemia and non-Hodgkin lymphoma have the highest mortality rates. Older age, cardiac diseases, and continuation of ongoing active therapy for hematological cancer are the independent risk factors for mortality in hematological malignancy patients with COVID-19.