PF746 IMPACT OF PRETRANSPLANTATION CYTOREDUNCTION STRATEGY AND PROGNOSTIC MUTATIONS IN ACUTE MYELOID LEUKEMIA WITH MYELODYSPLASTIC‐RELATED CHANGES
Authors: Tien F.‐M. , Tsai C.‐H. , Liao X.‐W. , Liu J.‐H. , Hou H.‐A. , Tang J.‐L. 
Published: June 2019

Background:

Acute myeloid leukemia with myelodysplastic‐related changes (AML‐MRC) represents a unique group in the 2016 WHO classification with unfavorable prognosis. Allogeneic stem cell transplantation (Allo‐SCT) is the only method for cure; however, the best pretransplantation cytoreduction strategy remains to be elucidated. Although previous studies showed comparable post‐SCT outcome for induction chemotherapy (IC) or Azacitidine in MDS/AML cohorts, the results should be interpreted cautiously because AML patients represent a minority part of the study population. Besides, previous studies have not comprehensively evaluated effect of prognostic mutations on post‐SCT outcome.

Aims:

In this study, we aim to investigate the impact of pretransplantation IC or Azacitidine on post‐SCT outcome. The post‐SCT outcome was also evaluated by incorporating a comprehensive mutation panel of 22 relevant genes.

Methods:

We recruited 223 AML‐MRC patients fulfilled the 2016 WHO classification diagnosed from 1996 to 2017. Therapy‐related AML was excluded. Cytogenetics was classified according to Medical Research Council criteria. The mutation status of 22 relevant genes was determined by Sanger sequencing and/or next generation sequencing. Clinical response was defined by 2006 IWG criteria. We examined a novel composite end point of GVHD‐free/relapse‐free survival (GRFS), in which events include grade 3–4 acute GVHD, systemic therapy‐requiring chronic GVHD, relapse, or death. Eighty‐three patients received allo‐SCT, and the conditioning regimen was either myeloablative (n = 17), reduced intensity (n = 58) or TBI based (n = 8). The donors were sibling (n = 37), haplo‐identical (n = 18) or HLA‐matched unrelated (n = 28).

Results:

The median age was 47 (range 17–72). The most frequent mutation was U2AF1, followed by NRAS, TET2, KRAS, and ASXL1 mutations. Nighty seven patients received IC and 66 patients received Azacitidine. The response rate was 41.2% in IC group and 26.2% in Azacitidine group. Of the 83 patients who underwent allo‐SCT, 56 received IC before transplantation, 19 patients had azacitidine and 8 received upfront SCT. Post‐SCT relapse rate was 58.9% in IC group and 63.2% in Azacitidine group. With a median follow up of 65.5 months from allo‐SCT, 3‐year outcomes in the IC, Azacitidine and upfront SCT groups were 50%, 23%, and 25% for overall survival (OS), 35%, 9%, 25% for GRFS. The OS and GRFS were significantly better in IC than Azacitidine group (P = 0.032, P = 0.019) (Figure 1A). Taking account of the SCT status, the estimated 3‐year overall survival (OS) was 30% in the azacitidine responders but 0% in non‐responders. For IC group, SCT at CR1 and outside CR1 had a 3‐year survival of 36% and 34% respectively. Presence of U2AF1, RUNX1, RAS pathway mutations (NRAS, KRAS), and P53 affect the post‐SCT outcome (Figure 1B). After adjustment for age, cytogenetic risk, donor, conditioning regimen and mutation status, IC group still had better OS (P = 0.01, HR 0.337, CI 0.148–0.766), GRFS (P = 0.028, HR 0.399, CI 0.176–0.905) compared to the Azacitidine group.

Summary/Conclusion:

The results showed that pre‐SCT therapy with IC is associated with a significantly better post‐SCT OS and GRFS than Azacitidine in AML‐MRC patients. Presence of prognostic mutations also predict distinct post‐SCT outcome.

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