War of the Cords: Optimising Graft-versus-Leukaemia in Double Cord Blood Transplantation

War of the Cords: Optimising Graft-versus-Leukaemia in Double Cord Blood Transplantation

In double cord blood transplantation, one unit engrafts and the other is rejected—but the losing unit might be doing more than previously imagined. A 2025 Blood Advances study from the Eurocord–EBMT registry reveals how the immunological battle between cord units can be redirected against leukaemia, particularly when the patient and losing unit share the right HLA mismatches. In this episode, we unpack the elegant biology behind this unintended vaccine effect, explore the surprising lack of excess GVHD, and consider what these findings mean for unit selection in high-risk disease. Could the losing graft be the key to preventing relapse? Episode Type: Deep dive intended for leukaemia and transplant health care professionals Reference: Wynn R, et al. Impact of shared HLA determinants between patient and losing cord blood unit on relapse after double cord blood transplantation. Blood Adv. 2025 May 2:bloodadvances.2025015938. doi: 10.1182/bloodadvances.2025015938. Epub ahead of print. PMID: 40315369.

Deep Dive: Paediatric/AYA AML Transplant Decisions in the Molecular Era

Which children and young adults with acute myeloid leukaemia should receive transplant in first remission? This episode explores a landmark 2025 analysis from the Children's Oncology Group that revisits this longstanding question through a contemporary molecular lens. Huang and colleagues, publishing in the Journal of Clinical Oncology, analysed outcomes for over 1,400 patients from the AAML0531 and AAML1031 trials—studies that enrolled patients up to age 29. By retrospectively applying contemporary molecular risk criteria from the current AAML1831 trial, including newly recognised adverse genetic lesions and measurable residual disease thresholds, they revealed striking patterns in transplant benefit across redefined risk groups. We unpack how this molecular reclassification informs our understanding of transplant outcomes, from the substantial improvements in disease-free survival for most high-risk patients to the unexpected findings in certain subgroups like monosomy 7. Along the way, we explore what these retrospective insights might mean for clinical practice in the genomic era of AML management—from approaches to molecular profiling at diagnosis to considerations around transplant timing in first remission. Episode type: Deep Dive—intended for leukaemia and transplant health care professionals or scientists involved in AML diagnostics or research. Reference: Hematopoietic Stem Cell Transplantation Outcomes for High-Risk AML: A Report From the Children’s Oncology Group by Huang BJ et al., Journal of Clinical Oncology, 2025. DOI: 10.1200/JCO-24-01841 [https://doi.org/10.1200/JCO-24-01841]

Rapid Review: Paediatric/AYA AML Transplant Decisions in the Molecular Era

Which children and young adults with acute myeloid leukaemia should receive transplant in first remission? In this Rapid Review, we explore a landmark analysis by Huang et al., published in the Journal of Clinical Oncology in April 2025. Reclassifying over 1,400 patients using AAML1831 criteria, the study offers a contemporary perspective on who gains from transplant—and who doesn't. The results are compelling: disease-free survival doubles for most molecularly defined high-risk patients, while those with monosomy 7 or 5 continue to fare poorly despite transplant. This three-minute overview highlights key findings and clinical implications, including donor timing, MRD integration, and the future role of targeted agents. The over-arching message is clear—biology now defines benefit. Episode type: Rapid Review of a key paper for anyone interested in AML biology or treatment Reference: Hematopoietic Stem Cell Transplantation Outcomes for High-Risk AML: A Report From the Children’s Oncology Group by Huang BJ et al., Journal of Clinical Oncology, 2025. DOI: 10.1200/JCO-24-01841 [https://doi.org/10.1200/JCO-24-01841]

First-Line Ven/Aza/Revumenib for AML?

Could targeting the menin–KMT2A axis up front improve outcomes in older adults with NPM1-mutated or KMT2A-rearranged AML? In this episode, we examine new phase I data from Zeidner and colleagues, published in The Journal of Clinical Oncology in June 2025, investigating revumenib in combination with azacitidine and venetoclax for newly diagnosed patients ineligible for intensive therapy. We explore the shared biological mechanism linking these two subtypes, the rationale for adding menin inhibition to ven/aza, and early results—including high remission rates, MRD nuances, and challenges around myelosuppression and treatment delays. How do these outcomes compare to VIALE-A? Could molecular MRD clearance inform future consolidation strategies? And where might this triplet fit among the growing field of ven/aza-based combinations? Episode type: Deep Dive potentially relevant to anyone carrying for acute leukaemia patients or interested in menin inhibitors more generally.

Targeting Menin in Acute Leukaemia: AUGMENT-101 Results

Building on our earlier Biology Tangent episode on menin inhibition, this clinical deep-dive explores the pivotal AUGMENT-101 trial results that led to FDA approval of revumenib — the first licensed menin inhibitor for acute leukaemias. Revumenib has shown meaningful activity in relapsed or refractory KMT2A-rearranged and NPM1-mutated acute leukaemias, illustrating how targeting transcriptional dependencies can restore differentiation, even in heavily pretreated patients. We examine key efficacy data, including CR/CRh rates of 23 percent — exceeding historical expectations — with nearly 40 percent of responders proceeding to transplant. The episode also explores biomarkers of response, such as IDH co-mutations; the expected safety profile, marked by differentiation syndrome and QTc prolongation; and emerging resistance mechanisms likely to influence future therapeutic development. Episode type: Deep Dive suitable for anyone involved in caring for acute leukaemia patients, or interested in menin inhibitors generally.