Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Conflicting data exist on the impact of mismatched unrelated donor (MMUD) compared to matched unrelated donor (MUD) in hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy), highlighting the need for disease-specific research. We conducted a retrospective analysis of donor characteristics in 350 patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) who received 8/8 human leukocyte antigen (HLA)-matched MUD and 7/8 HLA-matched MMUD. The primary endpoint was leukemia-free survival (LFS).

Limited Diagnostic and Therapeutic Value of Chest X-Rays in Hematological Patients With Febrile Neutropenia.

Background: In hematological patients with febrile neutropenia, chest X-rays are frequently performed to exclude possible pulmonary infections. However, the diagnostic and therapeutic value of this imaging remains unclear.

Methods: We conducted a retrospective observational cohort study over a 2-year period, examining episodes of febrile neutropenia in adult patients treated with myelosuppressive chemotherapy.

Real-time data in cancer registries: Validation of an automated data extraction system.

Timely surveillance of cancer treatment requires real-time integration of electronic health records (EHR) data into population-based registries. We validated data from the Datagateway, an automated system that harmonizes structured EHR data across hospitals into a common model to support near real-time enrichment of the Netherlands Cancer Registry (NCR). Data from patients with acute myeloid leukemia, multiple myeloma, lung cancer, and breast cancer were extracted via the Datagateway and compared to NCR data and EHR source data.

Utility of IDH1/2 mutations as biomarkers for detection of measurable residual disease in acute myeloid leukemia.

Molecular measurable residual disease (MRD) assessment in acute myeloid leukemia (AML) patients has been established for only a few specific markers, i.e. mutant NPM1 and FLT3-ITD.

Allogeneic hematopoietic cell transplantation for older patients with Philadelphia-positive acute lymphoblastic leukemia. A study by the Acute Leukemia Working Party of the EBMT.

The role of allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) is not well established. In this retrospective analysis we evaluated outcomes of 566 patients with median age of 60 (range 55-76) years treated in first complete remission with allo-HCT from either a matched sibling (n = 138), unrelated (n = 343) or haploidentical (n = 85) donor between the years 2016 and 2022. The probability of overall survival (OS) and leukemia-free survival (LFS) at 2 years was 71% and 59.

Impact of pre-transplant induction cycles on post-transplant outcomes in patients with ALL: a study from the ALWP EBMT.

The impact of the number of induction cycles required to achieve first complete remission (CR1) on transplant outcomes in adult acute lymphoblastic leukemia (ALL) patients remains unknown. We conducted a retrospective EBMT registry analysis (2000-2022) of ALL patients who underwent transplantation in CR1 after one (n = 2038), two (n = 296), or three or more (n = 110) induction cycles. Median age was 40 years (range 18-73); 79% had B-ALL.

Challenging the Adverse Label: Diverse Outcomes of ELN 2022 Adverse Cytogenetic Subgroups in Acute Myeloid Leukemia Patients Allografted in First Remission: From EBMT ALWP.

According to the European LeukemiaNet (ELN) 2022 classification, acute myeloid leukemia (AML) patients with intermediate or adverse risk are offered allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission. In this EBMT study, we included 1735 adult AML patients with ELN-2022 adverse-risk cytogenetics allografted between 2010 and 2022 in first remission (67% de novo AML, median age 56 years). Eleven non-overlapping adverse-risk cytogenetics groups were defined.

Comparability of external and internal control patients for the prospective randomized HOVON-103 trial in older AML patients.

Real-world data (RWD) previously contributed to post-marketing regulatory decision-making, but are currently also considered as external controls to single-arm trials. The use of RWD control data may be compromised by methodological issues, urging validation of RWD control cohorts. Two external control cohorts of newly diagnosed acute myeloid leukaemia patients, one registered by the HARMONY Alliance (HA) and one by the Netherlands Cancer Registry (NCR), were compared to the control arm of the randomized HOVON-103 trial (H103 controls).

A revised prognostic model for patients with acute myeloid leukemia and first relapse.

Most patients with acute myeloid leukemia (AML) may obtain remission upon induction chemotherapy, but relapse is frequent and associated with poor survival. Previous prognostic models for outcomes after relapse lacked analysis of comprehensive molecular data. A validated prognostic model integrating clinical, cytogenetic, and molecular variables may support treatment decisions.

Autologous stem cell transplantation for adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission. A study by the Acute Leukemia Working Party of the EBMT.

Background: The role of autologous hematopoietic stem cell transplantation (AHSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL) remains controversial. The aim of this retrospective study was to analyze results of AHSCT and to identify prognostic factors.

Methods: Overall, 700 patients transplanted in first complete remission between the years 1999-2020 were included.

Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia With Myelodysplasia-Related Genetic Features: Relevance of the Genetic Underlying Category. A Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the EBMT.

Patients (pts) with myelodysplasia-related AML (MR-AML) are now genetically recategorized, with three different groups in the International Consensus Classification: AML with mutated TP53 (TP53-AML), with myelodysplasia-related gene mutations (MR-GM AML), and with myelodysplasia-related cytogenetic abnormalities (MR-CG AML). Moreover, TP53-AML is determined by the presence of an additional complex karyotype (TP53-mut CK and non-CK AML, respectively). Nonetheless, the relevance of this classification to transplantation outcomes is largely unknown.

Cytogenetic and molecular risk-driven conditioning intensity in acute myeloid leukemia patients undergoing stem cell transplantation with post-transplant cyclophosphamide: a study from the acute leukemia working party of the EBMT.

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD.

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Double mutant DNMT3A AML: a unique subtype experiencing increased DNA damage and poor prognosis.

Mutation of DNMT3A, encoding a de novo methyltransferase essential for cytosine methylation, is a common early event in clonal hematopoiesis (CH) and adult acute myeloid leukemia (AML). Spontaneous deamination of methylated cytosines damages DNA, which is repaired by the base excision repair (BER) enzymes methyl-CpG binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Congenital MBD4 deficiency has been linked to early-onset CH and AML and is marked by exceedingly high levels of DNA damage and mutation of DNMT3A.

The role of allogeneic stem cell transplantation in acute myeloid leukemia with translocation t(8;16)(p11;p13).

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease-defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML.

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion.

Externally Controlled Studies Using Real-World Data in Patients With Hematological Cancers: A Systematic Review.

Importance: The use of real-world data (RWD) external control arms in prospective studies is increasing. The advantages, including the immediate availability of a control population, must be balanced with the requirements of meeting evidentiary standards.

Objective: To address the question of whether and to what extent the methods of RWD studies compare to standard methods used in randomized clinical trials.

Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi-state modeling.

Background: We recently reported results of the prospective, open-label HOVON-100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first-line treatment with or without clofarabine (CLO). No improvement of event-free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity.

Aim: In order to investigate the effects of CLO in more depth, two multi-state models were developed to identify why CLO did not show a long-term survival benefit despite more MRD-negativity.

Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT.

There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete remission (CR1 or CR2). The primary end point was leukemia-free survival (LFS).