Chrysavgi Lalayanni

Background: Treosulfan combined with fludarabine (FluTreo) has emerged as a reduced-toxicity alternative to conventional myeloablative conditioning in allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and related myeloid malignancies. Purpose: This study evaluates the safety, engraftment kinetics, and long-term outcomes of the FluTreo FT14 regimen in a real-world adult cohort. Materials and Methods: We conducted a prospective cohort study of 186 consecutive adults (18–70 years) undergoing allo-HCT between January 2015 and December 2024. Eligible diagnoses included de novo or secondary AML, myelodysplastic syndrome, and myelofibrosis. All received peripheral blood stem cells from matched or mismatched unrelated donors, HLA-matched siblings, or haploidentical relatives. The FT14 protocol comprised fludarabine 150 mg/m² over five days and treosulfan 42 g/m² over three days, with rabbit antithymocyte globulin (5 mg/kg) for unrelated grafts. Primary endpoints were neutrophil and platelet engraftment, donor chimerism, incidence of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM). Kaplan–Meier, Cox regression, and Fine and Gray models were applied. Results: Median age was 59 years; diagnoses included de novo AML (43%), secondary AML (16%), MDS (25%), and MF (16%). Neutrophil and platelet engraftment medians were 10 and 12 days, respectively. Full donor chimerism (≥99%) was achieved by day 31. Grade III conditioning-related toxicity occurred in 3.2% of cases. Five-year cumulative incidences of grade II–IV acute GVHD and moderate/severe chronic GVHD were 37.6% and 30.6%. Median follow-up was 16.3 months; relapse occurred in 25.3%. Five-year OS and DFS were 71% and 49% overall (75.8% and 59% in CR1), with TRM of 15.3%. Disease relapse and acute GVHD independently predicted inferior OS, and acute GVHD predicted TRM. Conclusions: The FluTreo FT14 regimen achieves rapid engraftment, universal high donor chimerism, low severe toxicity, and durable survival, supporting its use as a myeloablative, reduced-toxicity conditioning option in myeloid malignancies.

Background/Objective: The prognostic impact of additional cytogenetic aberrations and molecular abnormalities (such as MDS-related mutations, mutations in myeloid genes and the KRAS/NRAS mutations) in patients with NPM1- and/or FLT3-ITD-mutated AML remains elusive. Methods: This retrospective, multicentre study of real-world data aimed to investigate the impact of these mutations and cytogenetic abnormalities on the prognosis of patients with NPM1- and/or FLT3-ITD-mutated AML, treated with intensive chemotherapy. Results: In a cohort of 161 patients, the only parameters identified to affect the outcomes (EFS and OS) were the age of the patient, primary refractory disease, the presence of a NPM1 mutation and the use of allogenic stem cell transplantation (allo-SCT) within the first complete remission. More specifically, ages below the median conferred significantly improved outcomes, whereas primary refractory disease exhibited a negative correlation with the EFS and OS. Subsequent subgroup analysis, stratifying patients into three groups (Group 1: NPM1^mutated/FLT3^wt; Group 2: NPM1^mutated/FLT3^mutated; Group 3: NPM1^wt/FLT3^mutated). revealed that allo-SCT in CR1 improved the outcomes (EFS and OS) in Groups 2 and 3, but had no additional impact in Group 1. Conclusions: Age, primary refractory disease and allogenic stem cell transplantation in the first complete response were found to have a prognostic impact on outcomes, Interestingly, no significant association was detected between the poor prognostic cytogenetic abnormalities or the presence of additional mutations in myeloid genes, MDS-related genes or KRAS/NRAS genes and the outcomes in any group of patients.

Introduction: According to the National Cancer Institute of the NIH, acute myeloid leukemia (AML) is a rapidly growing cancer with a large quantity of myeloblasts. AML is most often observed in adults over the age of 35, accounting for 1% of all cancer types. In 2023, the number of new cases being reported was estimated to reach around 20,380 in total and the rate of mortality in the same year was 1.9%, or 11,310 cases, in the US. Purpose: This scoping study aims to extensively assess and explore the degree of cardiotoxicity in patients with AML that can be caused due to pharmaceutical treatments prescribed by hematologists. This is achieved by performing extensive searches of different scientific databases including PubMed, Scopus, and ScienceDirect. Results: A variety of options are available that are summarized in tables included herein, with each having their advantages and risks of adverse effects, among these being cardiotoxicity. Important medications found to play a significant role include gemtuzumab ozogamicin, venetoclax, and vyxeos. Conclusions: It is understandable that being familiar with all the treatment options available and every potential adverse effect is impossible. However, hematologists and, in general, physicians must try to be updated with the most recent information released to improve the quality of life of their patients and minimize the risk of additional complications.

(1) Background: Autologous, allogeneic hematopoietic cell transplantation (HCT) and other cellular therapies, including CAR T cell and gene therapy, constitute a cornerstone in the management of various benign and malignant hematological disorders. Invasive fungal infections (IFD) remain a significant cause of morbidity and mortality in HCT recipients. Therefore, we investigated the prevalence and risk factors of IFD following HCT and other cellular therapies in an era of novel antifungal prophylaxis. (2) Methods: In this study, we retrospectively enrolled adult HCT recipients who were treated at our JACIE-accredited center according to standard operating procedures over the last decade (2013–2022). (3) Results: 950 patients who received cellular therapies were studied. None of the 19 CAR T cell and neither of the two gene therapy recipients developed IFD whereas 3/456 autologous HCT recipients who suffered from primary refractory/relapsed lymphomas presented with probable IFD. Overall, 11 patients who received allogeneic HCT experienced probable IFD, possible IFD was found in 31/473, and IFD was proven in 10/473. A second IFD episode was present in three patients. Four-year OS was significantly lower in proven compared to probable IFD (p = 0.041) and was independently associated with HCT-CI (p = 0.040) and chronic GVHD (p = 0.045). (4) Conclusions: In this real-world cohort, the prevalence of proven and probable IFD in an era of novel antifungal prophylaxis was found to be relatively low. However, IFDs were associated with poor outcomes for patients who received allogeneic HCT.

Opposing acute lymphoblastic leukemia, sparse data about AYAs with acute myeloid leukemia (AML) is available. Overall, 125 AYAs (age 10–35 years) treated during the last two decades were evaluated and compared to 385 older patients. CBF leukemia was more frequent in AYAs (21.6% vs. 8%, p < 0.001); however, many presented high-risk features. AYAs showed improved complete remission rate (CR, 80% vs. 65%, p = 0.01), lower cumulative incidence of relapse and TRM and longer survival (5 year-OS 53% vs. 24%, p < 0.0001), observed mainly in intermediate-risk karyotype. Adolescents displayed even better outcomes (5 year-OS 69%). AlloHCT in CR1 was beneficial for nonadolescent AYAs (5 year-OS 66.7% vs. 44.4% without HCT, p = 0.04). Among 50 APL patients, 19 AYAs experienced better outcomes than older, mainly attributed to reduced treatment-related mortality (TRM, 5% vs. 19%, p = 0.1). We observed an important (>10%) survival gain for AYAs during the last decade. However, AYAs have still unmet needs to obtain optimal cure rates.

The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.