20 April 2020

People whose acute leukaemia becomes refractory to initial or re-induction chemotherapy can tolerate ‘total therapy’ well, according to a new population-based study.

Research led by a team at the Peking University Institute of Haematology, China, analysed the outcomes of 932 consecutive patients who underwent transplantation during relapse or primary induction failure, to evaluate the impact of more intensive conditioning or safer donor lymphocyte infusion in relapsed/refractory acute leukaemia (RRAL).

Study leader Professor Xiao-Jun Huang said their findings indicated that patients with RRAL can tolerate both prophylactic/pre-emptive donor lymphocyte infusion (p/pDLI) and intensified myeloablative conditioning (intenseMAC) and achieve a reasonable outcome.

The three-year leukaemia-free survival rate was 56% for patients receiving both interventions and 30% for those receiving neither therapy.

Existing strategies to decrease post-transplant relapse for patients with RRAL include more effective pre-transplant conditioning, safer donor lymphocyte infusion (DLI), and improved donor selection (including haploidentical donor). However, the study authors say that relevant real-world data to provide evidence for the effectiveness of these measures is scarce.

What’s more, in the two largest population-based studies coming from international registries, most patients underwent haematopoietic cell transplant from matched sibling donors or unrelated donors, while patients receiving haploidentical donations account for less than 10% of the population.

The authors said it is vital to understand the influence of treatment-relevant variables in patients with active acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) in the therapeutic decision-making process.

Prof Huang and his team performed multivariate analyses to evaluate the effectiveness for patients of intensified conditioning, DLI, or the combined treatment, among sibling and haploidentical recipients.

They found that p/pDLI was associated with significantly higher leukaemia-free survival than non-DLI for both AML and ALL patients, without increasing non-relapse mortality.

IntenseMAC was linked to significantly lower relapse and higher survival than non-intensified MAC in ALL, despite higher non-relapse mortality rates. There was no impact of intenseMAC in AML.

p/pDLI had superior outcomes in both sibling and haploidentical transplant, while intenseMAC only had influence on outcomes of patients receiving stem cells from a matched sibling donor.

Prof Huang said: “So, RRAL patients receiving ‘total therapy’ by way of p/pDLI and intenseMAC have an improved chance for leukaemia-free survival, with p/pDLI being safer with a more extensive impact relative to intenseMAC.”


Source: Wang Y, Liu QF, Wu DP, Wang JB, Zhang X, Wang HX, Gao F, Wang SQ, Sun ZM, Ouyang J, Xu KL, Gao SJ, Xu LP, Yan CH, Huang XJ (2020) “Impact of prophylactic/preemptive donor lymphocyte infusion and intensified conditioning for relapsed/refractory leukemia: a real-world study”, Sci China Life Sci, doi: 10.1007/s11427-019-1610-2

 

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