Flamsa Reduced-Intensity Conditioning Regimen in AML Patients – Role of Re-Induction and Disease State Prior to Transplant

Reduced intensity conditioning (RIC) regimens as compared to myeloablative protocols have demonstrated lower toxicity profiles at similar efficacy in the context of allogeneic haematopoietic stem cell transplantation (allo-SCT) for patients with acute myelogenous leukaemia (AML) in first or second remission. In addition, the FLAMSA RIC regimen, combining a cytoreductive part and a transplant-conditioning part, has been described to be efficacious in patients with refractory disease. Re-induction treatment after AML relapse or refractory disease is often accompanied by severe, in particular, infectious complications such as fungal pneumonia caused by long neutropenic phases, precluding a significant proportion of patients from completing allo-SCT. To have a closer look on the role of re-induction therapy prior to transplant, we retrospectively analysed clinical data of 118 consecutive patients with AML after allogeneic stem cell tranplantation following FLAMSA conditioning at our center. No prophylactic donor lymphocyte infusions were administered.

Median age of the cohort was 53 years (19-73 years). Donors were matched related, matched unrelated or mismatched unrelatred in 33, 49 and 18% of the transplants. Complete remission prior to transplant was detected in 29% and 21% of the patients after induction or re-induction, respectively. Twenty-five percent of the patients were transplanted with blast persistence, both in the group of patients after first induction and re-induction treatment. Median follow-up was 27 months.

The 4-yr overall survival of the whole cohort is 44% with a 4-yr relapse-free survival of 42%. Cumulative incidence of relapse was 26, 30 and 40% at one, two and four years, respectively. Cumulative incidence of non-relapse mortality (NRM) was 15, 18 and 18% at one, two and four years, respectively.

There were no significant differences regarding overall and relapse-free survival for patients transplanted in CR1, CR2 or blast persistence after induction treatment. Patients who failed remission after re-induction therapy showed significantly worse overall and relapse-free survival (p=0,049 and 0,003, repectively, log-rank test). NRM was similar in all cohorts.

FLAMSA is a highly effective conditioning regimen for AML patients even not in CR. Thus, the decision for re-induction therapy prior to allogeneic SCT has to be weighted against the potential toxicity of this approach.