Treatment outcome after induction chemotherapy before allogeneic hematopoietic SCT in patients with advanced MDS

Abstract

6502 Background: The need for induction chemotherapy (IC) before allogeneic hematopoietic stem cell transplant (alloSCT) in advanced myelodysplatic syndrome (MDS) remains controversial. Methods: This is a retrospective analysis of the remission rate in 99 patients with advanced MDS (≥5% marrow blasts) and acute myeloid leukemia (AML, ≥ 20% blasts) evolving from MDS, who were treated with IC before receiving cytoreduction for SCT. These patients were referred to MSKCC for alloSCT from 6/1980 to 10/2004, and subsequently underwent an unmodified or T cell-depleted (TCD) SCT from a matched or mismatched related or unrelated donor after myeloablative cytoreduction in the majority. Results: All patients had MDS at diagnosis: 33% had high risk (HR), 22% intermediate risk (IR) and 42% good risk (GR) cytogenetics; 38% had HR, 32% IR-2 and 25% IR-1 IPSS. The median age was 43 (range 2–66). 76% had primary and 24% had secondary MDS (chemotherapy or radiation). At the time of IC, 64% had frank AML, 33% RAEB-1 and 2, and 3% CMML-2. A combination of an anthracycline (Ac) and standard dose (SD) cytarabine (AraC) was administered to 53% of the patients. Other regimens included Ac with high dose (HD) AraC (15%), Ac with SD AraC and etoposide (15%), HD AraC alone (8%), and HD AraC with etoposide (4%). 26% of patients required a second line regimen and 4% went on to a third. None of the patients died of complications due to IC. CR was achieved in 60% of patients overall (64% in those receiving Ac + SD AraC ± etoposide and 52% for HD AraC ± Ac ± etoposide). The CR rate was 65% in primary and 42% in secondary MDS, and was similar in adults (60%) and children (56%). CR rates were 44% in HR, 68% in IR, and 65% in GR cytogenetics; 58% in HR, 59% in IR-2, and 60% in IR-1 IPSS. According to disease status at IC, the CR rate was 60% for RAEB-1 and 2 and 59% for AML. 12% of complete responders relapsed prior to cytoreduction for SCT. 49% of all patients underwent a TCD SCT from an HLA identical sibling. There are no long term survivors after SCT in patients who did not achieve CR after IC, in contrast to 47% overall survival at 10 years for responders. Conclusions: IC in advanced MDS is associated with a high rate of CR. IC before cytoreduction for SCT is an effective approach to reduce the burden of disease particularly prior to TCD SCT. No significant financial relationships to disclose.