Hematology

ASH 2026 standardizes frontline management for AYA ALL

These ASH guidelines recommend pediatric-inspired, asparaginase-containing regimens as preferred frontline therapy for adolescents and young adults with ALL over adult-type protocols. They emphasize the need for intensive supportive care and close monitoring given regimen-associated toxicities and adherence challenges in this age group. Allogeneic HSCT in first remission is not routinely advised and is reserved for biologically high-risk disease or inadequate early treatment response. The panel supports incorporating targeted agents into frontline therapy but notes that optimal combinations, timing, and sequencing require further study. 1

Conventional vs HMA/LDAC±venetoclax in older AML: systematic synthesis

This systematic review of 21 studies compared 7+3-type induction and post-remission therapy with HMA- or LDAC-based strategies in older adults with newly diagnosed AML. Conventional therapy increased complete remission rates versus HMA/LDAC monotherapy and may reduce mortality and recurrence, at the expense of more severe toxicities. Against HMA or LDAC combined with venetoclax, very low-certainty evidence suggested conventional therapy may lower 1-year mortality and increase allogeneic transplant use. Differences in remission, recurrence, and severe toxicities versus venetoclax combinations were inconsistent, supporting equipoise for randomized head-to-head trials. 2

Long-term outcomes with fixed-duration ibrutinib+venetoclax in R/R CLL

In this phase II study, 79 treated patients with relapsed or refractory CLL received three cycles of ibrutinib then 24 cycles of ibrutinib plus venetoclax. Most evaluable patients had unmutated IGHV, and over one third carried del(17p) or TP53 mutation, indicating a high-risk population. The regimen achieved a 67% CR/CRi rate and 61% bone marrow undetectable MRD at 10⁻⁴ sensitivity, indicating deep remissions. With a median follow-up of 95.5 months, the estimated 7-year progression-free survival was 63.3%, with manageable rates of grade ≥3 neutropenia and thrombocytopenia. 3

Dual CD19/CD22 CAR-T±ASCT offers durable control in TP53-altered B-NHL

This study followed 122 patients with relapsed or refractory aggressive B-cell NHL treated with dual CD19/CD22 CAR-T alone or after autologous transplantation for a median 77.8 months. TP53 alterations were present in nearly half of patients but did not significantly affect overall or progression-free survival in either treatment cohort. Sequential ASCT followed by CAR-T produced higher 5-year overall and progression-free survival than CAR-T alone, with limited nonrelapse mortality. Serious infections beyond three months and secondary malignancies were infrequent, supporting favorable long-term safety for this dual-target CAR-T approach. 4