Blood cancers

Not too little, not too much: the Goldilocks zone for pre-HSCT chemo

A second chemotherapy cycle before haematopoietic stem cell transplantation (HSCT) may improve survival in children with relapsed AML.

A retrospective analysis of data from the Australasian Bone Marrow Transplant Recipient Registry between 1998 and 2013 found two chemotherapy cycles improved overall survival compared to just one or three or more cycles.

Two cycles appeared to “strike a balance between disease control and the potential for increased toxicity and chemoresistance”, the researchers said.

The study of 83 children found about half (52%) had two cycles of chemotherapy prior to HSCT, 30% had only one cycle, 11% had three cycles and 7% had four.

It found the 5-year overall survival (OS) for patients who underwent two cycles of chemotherapy was 73.3%, compared to 46.5% for those who had just one cycle and 40% for those who had three or more cycles.

Just over half the deaths (55%) in the cohort were due to relapse or disease progression with graft-versus-host disease, organ toxicity, infection and other transplant related deaths making up the remainder.

The study also examined the effect of additional cycles of chemotherapy after achievement of measurable residual disease (meRD) negativity.

“Similar to the overall patient group, a statistically significant survival benefit was seen in the group receiving two cycles of chemotherapy, having a 5-year OS of 79.4%, compared to 46.4% for those who proceeded to transplant after cycle 1, and 37.5% for those who had three or more cycles.”

The researchers said their study shed some light on the question of how many cycles of chemotherapy were optimal for relapsed patients prior to HSCT.

“Reinduction chemotherapy in relapsed childhood AML leaves little room for treatment intensification, and so, in the absence of novel therapies, there are limited options for pre-transplant disease reduction besides additional chemotherapy cycles, which also risks increased treatment-related morbidity and mortality.”

“Our retrospective analysis demonstrates a statistically significant survival advantage for those patients transplanted in CR2 who received two cycles of chemotherapy pre-HSCT, compared to those who received one or at least three cycles, both in the whole cohort as well as in those patients with no detectable disease after the first cycle.”

“It was also evident that relatively fewer patients became MeRD negative with each course of chemotherapy. Within the constraints of small numbers, this supports the notion that clearance of MeRD in relapsed AML, like achievement of CR status, becomes more difficult with each subsequent cycle.”

They noted it was possible that the inferior outcomes in patients receiving three or more cycles of chemotherapy may have been influenced by difficulty and/or delay in finding an optimal donor.

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