For children and young adults with acute myeloid leukaemia (AML) and measurable residual disease (MRD) negativity, proceeding to allogeneic hematopoietic stem cell transplant (HSCT) after two rounds of chemotherapy is as effective as completing a third cycle prior to HSCT, yielding similar transplant outcomes, according to a multicentre retrospective study.
Receipt of three vs two chemotherapy cycles prior to HSCT was not associated with better overall survival (OS) or leukaemia-free survival (LFS) or reduced relapse, reported first study author Dr Lindsey Murphy from City of Hope in Duarte, California, US.
“Findings were consistent regardless of timing of achieving MRD negativity,” Murphy said.
In the cohort of patients achieving MRD negativity after cycle 1, the 4-year OS rates were 77.9 percent among those who received two cycles of chemotherapy vs 65.2 percent among those who received three cycles prior to HSCT (p=0.17). The 4-year LFS rates were 74.3 percent vs 63.4 percent (p=0.16), respectively. [EHA 2026, abstract S136]
Over 4 years, relapse occurred in 14.5 percent of patients in the 2-cycle group and in 26.7 percent of those in the 3-cycle group (p=0.091), demonstrating a nonsignificant trend toward more relapse with more cycles of chemotherapy, according to Murphy. There was no significant difference in treatment-related mortality between the 2- and 3-cycle groups (adjusted odds ratio [aOR], 7.25, 95 percent confidence interval [CI], 0.79–66.85; p=0.081).
Similar results were observed in the cohort of patients achieving MRD negativity only after cycle 2. The 4-year OS rates were 74.7 percent in the 2-cycle group vs 62.1 percent in the 3-cycle group (p=0.23), while the 4-year LFS rates were 59.7 percent vs 54.5 percent (p=0.36), respectively. The 4-year relapse rates were 35 percent vs 38 percent (p=0.43), respectively, with no significant between-group difference in treatment-related mortality (aOR, 0.43, 95 percent CI, 0.03–7.06; p=0.55).
“Historically, three chemotherapy cycles have been administered prior to HSCT. However, many centres now proceed more rapidly after fewer cycles once MRD negativity is achieved,” Murphy noted. “The results of this study challenge the paradigm that additional chemotherapy beyond MRD clearance improves HSCT outcomes for paediatric AML patients in their first complete remission.”
The study included 274 children and young adults (median age at diagnosis 12 years, median age at transplant 12.29 years, 51.1 percent male) with AML from 15 institutions across the US. Of the patients, 95 (34.7 percent) underwent HSCT after two chemotherapy cycles and 179 (65.3 percent) underwent transplant after three cycles. MRD negativity was achieved after cycle 1 in 149 patients (54.38 percent) and after cycle 2 in 125 (45.62 percent).
Disease-related characteristics were similar between the 2- and 3-cycle groups, except the number of chemotherapy cycles to achieve first complete remission and extramedullary disease presentation. A smaller percentage of patients achieved first complete remission after cycle 1 in the group that underwent transplant after 3 cycles of chemotherapy (68.2 percent vs 84.2 percent), and more patients in the 3-cycle than the 2-cycle group had extramedullary disease at diagnosis (34.6 percent vs 20 percent).
Transplant-related characteristics, such as stem cell source and donor type, were similar between the 2- and 3-cycle groups.
When outcomes were analysed in the combined MRD-negative cohort, 4-year OS rates did not significantly differ between the 2- and 3-cycle groups (p=0.060), as were 4-year LFS (p=0.083) and relapse (p=0.061) rates and treatment-related mortality (p=0.33).
Murphy said her team is currently conducting additional analyses to delineate the impact of additional disease and treatment-related factors that may influence these findings. “These include a subanalysis on high-risk patients; looking at certain individual cytogenetic risk groups like the FLT3 and KMT2A; and looking at donor features, chemotherapy and conditioning regimens, and post-transplant complications, among others.”