Alexandros Kanellopoulos

The optimal conditioning intensity for allogeneic hematopoietic stem cell transplantation (allo-HCT) in elderly acute myeloid leukemia (AML) remains elusive. We retrospectively analyzed 2900 AML patients aged ≥65 in complete remission who underwent allo-HCT from 2004 to 2021. Conditioning was classified as reduced-intensity conditioning (RIC: fludarabine with busulfan, melphalan, or treosulfan) or non-myeloablative (NMA: fludarabine with total body irradiation). Primary endpoints were overall survival (OS) and leukemia-free survival (LFS); secondary endpoints included non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and GVHD/relapse-free survival (GRFS). With follow-up censored to account for differences between arms, OS, LFS, and NRM at 2 years were similar between RIC and NMA on multivariable analysis. Peripheral blood stem cells (PBSC) were independently associated with superior OS (HR 0.67, p = 0.002) and LFS (HR 0.71, p = 0.008) versus bone marrow grafts. GRFS was equivalent between conditioning intensities, although RIC was associated with higher acute GVHD and NMA with higher extensive chronic GVHD. In exploratory analysis, OS and LFS were similar across RIC regimens (Flu/Bu2 as reference: Flu/Mel OS HR 0.91, p = 0.53; Flu/Treo OS HR 0.89, p = 0.42). In older AML patients in remission, RIC and NMA yield comparable survival and NRM; PBSC grafts may be associated with superior outcomes although this warrants validation.

The landscape of Allogeneic Haematopoietic Cell Transplantation (allo-HCT) for Chronic Myeloid Leukaemia (CML) remains dynamic with the advent of tyrosine kinase inhibitors (TKIs). There remains an absence of widely agreed evidence-based guidelines for post-transplant monitoring and relapse management. To evaluate current real-world practices for ‘high risk’ CML, the CML subcommittee of the Chronic Malignancies Working Party (CMWP) of the European Blood and Marrow Transplantation (EBMT) society developed an electronic survey, which was distributed to 39 EBMT-registered transplant centres in April 2024. Centres were chosen based on CML allo-HCT activity. Twenty-three centres (59%) responded, providing clinical perspectives into pre-transplant chemotherapy regimens, TKI use, ABL1 kinase domain mutation analysis, post-transplant monitoring, and their practice regarding sequencing/ integration of TKIs with donor lymphocyte infusions (DLI). Most centres conduct monthly BCR::ABL1 transcript monitoring during the first three months post-transplant, transitioning to quarterly assessments upon achieving a deep molecular response. TKI maintenance is widely adopted across centres, with treatment duration guided by molecular response, and TKIs are generally preferred over DLI for managing molecular relapse. However, DLI remains a valid option for TKI-refractory chronic-phase (CP)-CML relapse. Survey findings illustrate significant heterogeneity in practice, offering insights to inform research aimed at improving allo-HCT outcomes in CML.

Background Relapsed angioimmunoblastic T-cell lymphoma (AITL) following autologous transplantation carries poor prognosis. Reduced-intensity T-replete allogeneic transplant may provide durable disease control via immune-mediated graft effects. Methods We retrospectively analyzed 21 patients over the age of 50 with relapsed AITL who underwent reduced-intensity T-replete allo-HCT across three transplant centers between 2013 and 2022. Following salvage treatment, all patients experienced chemo sensitive disease and proceeded to transplantation. Responses were PET-based, and survival outcomes were assessed. Results All patients achieved hematologic engraftment, with 13 in complete metabolic remission and 8 in partial remission at the time of transplant. At a median follow-up of 7.55 years, OS was 100%, 81%, and 71% at 1, 2, and 5 years, respectively, with PFS of 95%, 95%, and 84%. Seven deaths occurred, four due to disease progression and three related to transplantation. Acute and chronic GvHD were observed in 30% and 22% of patients respectively. Five patients received donor lymphocyte infusion, showing a trend toward improved survival. Conclusion Reduced-intensity T-replete allo-HCT is a feasible and potentially curative therapeutic option for patients over 50 with chemo sensitive relapsed AITL after autologous transplantation. Early disease control and long-term remission suggest a clinically meaningful graft-versus-lymphoma (GVL) effect in appropriately selected individuals.

Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)–mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals. Median age was 61 years, and 36% had received ≥2 prior lines of therapy, including a FLT3 inhibitor in 41% and venetoclax in 24%. A median of 4 cycles of gilteritinib were administered, with 56% of patients requiring hospitalization in the first cycle (median, 10 days). Over half of patients required transfusion in each of the first 4 cycles. Complete remission (CR) was achieved in 21%, and CR with incomplete recovery (CRi) in a further 9%. Remission rates were lower for patients with FLT3–tyrosine kinase domain or adverse karyotype. Day-30 and day-60 mortality were 1% and 10.6%, respectively, and median overall survival was 9.5 months. On multivariable analysis, increasing age, KMT2A rearrangement, and complex karyotype were associated with worse survival whereas RUNX1 mutations were associated with improved survival. Twenty patients received gilteritinib as first salvage having progressed after first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials, but outcomes remain suboptimal, with more effective strategies needed.

The significance of serum beta-2 microglobulin (sβ₂m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ₂m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8–3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ₂m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ₂m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff (“normal versus high”). In multivariate analysis, sβ₂m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ₂m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ₂m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ₂m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a “normal versus high” cutoff set at 2.4 mg/L.

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with variant histopathology or aberrant immunophenotype is exceedingly rare and there is paucity of data with regards to its clinical characteristics and course. Case Report: Herein, we present three cases of NLPHL with aberrant immunophenotype or variant histopathological picture, which displayed distinct clinical and imaging findings. These case reports involved a patient with CD30 and CD20 positivity without Reed-Sternberg cells present, a NLPHL patient with aggressive, persistent disease activity with progressive transformation to germinal centres, and a patient with combined morphology of NLPHL and classical Hodgkin’s lymphoma. Conclusion: Aberrant immunophenotype/variant NLPHL might represent a distinct form of NLPHL, sharing characteristics with classical Hodgkin, non-Hodgkin lymphomas or benign, progressive transformation of germinal centre lymphadenopathy.