Global expert perspectives on the future of hematopoietic cell transplantation and cell therapies

Defining global priorities in hematopoietic transplantation and cellular therapy: a statement paper from EBMT Global ComMittee.

Hematopoietic cell transplantation, cellular and gene therapies, and (CAR)-T cells have revolutionized outcomes in hematologic disorders. However, major disparities persist in their availability, accessibility, and affordability, particularly in low- and middle-income countries (LMICs). The EBMT Global Committee aims to address these inequalities. A structured survey was distributed to EBMT members to identify regional and thematic priorities, assess current infrastructure, and assess willingness to contribute to global initiatives. Responses were analyzed descriptively and served as the basis for the current statement paper. A total of 145 responses from 43 countries were collected. Most respondents (67.1%) reported working in JACIE- or FACT-accredited centers. The highest priority regions for EBMT outreach were Eastern Europe (non-EU) (43.9%), Latin America (38.2%), and Africa (33.5%), followed by the Middle East (29.5%). The leading thematic priorities were education and training (74.3%), scientific collaboration (56.0%), and registry development (43.4%). Most respondents expressed willingness to actively contribute, particularly in educational activities (59.7%). Qualitative responses emphasized the need for practical guidelines, mentorship programs, telemedicine, virtual discussion/clinical rounds on difficult cases, and support for LMIC capacity building. The EBMT community strongly supports an expanded global role focused on education, capacity building, and collaboration in underserved regions.

Cellular therapy in mantle cell lymphoma: recommendations from the EBMT practice harmonisation and guidelines committee.

Cellular therapies, namely autologous hematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) and more recently, chimeric antigen receptor T-cell therapies (CART), play a major role in state-of-the-art treatment of mantle cell lymphoma (MCL). With numerous therapeutic innovations currently entering the MCL treatment landscape, guidance for indication, sequencing and application of cellular therapies is of key importance. To address this practical need, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonisation and Guidelines Committee convened an international expert meeting in Berlin on Sept 29/30, 2025. EBMT provided funding and logistical support. Two appointed chairpersons invited experts in MCL and cellular therapy, who completed three work packages devoted to the three types of cellular therapy. A literature search was performed beforehand and suitable published evidence was considered collectively in structured discussions and consensus-building exercises. The recommendations developed as a result of this process provide a sound basis for practical counseling and decision-making in the care of patients with treatment-naïve and relapsed/refractory MCL.

[Hematopoietic cell transplantation in the era of genome analysis].

Pharmacogenetic Profiling of Allogeneic Stem Cell Transplantation Patients: An Exploratory Descriptive Study

Background/Objectives: Patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are at high risk for severe disease and treatment-related complications and toxicities. Pharmacogenetic studies suggest that genetic variants can alter the response to several drugs critical to alloHCT outcomes, including tacrolimus and cyclophosphamide, potentially impacting toxicity and treatment outcomes. Methods: To assess the frequency of pharmacogenetic variants in AML/ALL patients undergoing alloHCT, we used a validated 11-gene pharmacogenetic panel in an exploratory descriptive study. We retrospectively genotyped 142 AML/ALL patients including two atypical chronic myeloid leukemia (aCML) patients, ≥18 years, who underwent alloHCT at our center between January 2020 and June 2024. Results obtained from 470 individuals in the Lifelines NEXT population cohort were used as controls. Results: Almost all patients carried at least one pharmacogenetic variant (97.2%), with a mean of 3.2 (standard deviation = 1.5) variants per patient. Variants known to influence tacrolimus metabolism (CYP3A4 and CYP3A5) were present in 26.8% of patients. Variants known to influence cyclophosphamide metabolism (CYP2B6, CYP2C9, CYP2C19) were present in 81.7% of patients. Variant frequencies did not significantly differ from controls. Conclusions: Actionable pharmacogenetic variants are highly prevalent in alloHCT-recipients. Future studies should investigate whether genotype-guided drug selection and dosing could improve outcomes in alloHCT recipients.

Accelerating Translation of NK Cell Therapies to the Clinic: A European Perspective

Adoptive immunotherapies have emerged as a promising strategy in the treatment of hematological malignancies. To date, seven chimeric antigen receptor (CAR)-T cell products have obtained market authorization in Europe for B-cell malignancies, where they have revolutionized treatment for eligible patients. In addition, natural killer (NK) cells and γδ T cells are of particular interest for cell-based therapies due to their strong intrinsic cytotoxicity and favorable safety profile. Addressing challenges facing the clinical translation of NK cell therapies was one of the issues discussed in the NK & ILC Symposium that took place in Freiburg, Germany from March 11 to 13, 2026, as the annual meeting of the NK & ILC study group of the German Society for Immunology (DGfI). Topics ranging from basic immunological research to technological innovations and clinical trial results were discussed during the 3-day conference, spanning over 40 presentations and 100 posters. A highlight of the conference was a workshop featuring short presentations and a panel discussion that focused specifically on the current challenges and future prospects of the clinical implementation of NK cell therapies; the findings of this workshop are summarized in this opinion paper. Graphical abstract

Clinical trial landscape and translational prospects of natural killer cell-based immunotherapy: an analysis based on the INFORMA database

Abstract Natural killer (NK) cell-based immunotherapy is an increasingly important cancer treatment strategy because of its innate cytotoxicity, allogeneic potential, and compatibility with off-the-shelf manufacturing. We analyzed 287 clinical trials identified in the INFORMA database to characterize the global development of NK-cell therapies across phases, regions, indications, combinations, cell sources, product origins, and engineering platforms. Most trials were planned or early-phase, and combination regimens were more frequent than monotherapy. The USA, China, and South Korea led clinical activity. Hematologic malignancies remained the principal testing ground, while lung, colorectal, and other solid tumors reflected broader expansion. Platform-level analysis showed a predominance of allogeneic products and rapid growth of CAR-engineered NK-cell trials after 2020. These findings indicate a transition from proof-of-concept adoptive transfer toward standardized, genetically programmable, off-the-shelf platforms. The principal challenge is shifting from manufacturing feasibility alone to durable biological activity. Future development should align cell engineering, combination partners, translational endpoints, and biomarker-guided patient selection with specific barriers involving persistence, tumor delivery, microenvironmental fitness, and immune escape.