Allogeneic stem cell transplant (allo-SCT) is a potentially curative option for high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Disease relapse after transplant is the major cause of treatment failure and is associated with a poor outcome. Intensive chemotherapy followed by donor lymphocytes infusion (DLI) or a second SCT may result in a durable response in some patients, but is associated with increased toxicity. More recently, a less aggressive therapy with hypomethylating agents (HA) has been reported to have activity in treatment of post-SCT relapse. We compared the treatment outcomes of intensive chemotherapy with that of HA. The primary end points were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression free survival (PFS). A total of 100 patients with AML in morphological evidence of relapse were included: 73 patients received chemotherapy and 27 patients received a HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least one DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% vs. 18.5%, p = 0.004) and a higher CR rate (40% vs. 7%, p= 0.002). The median OS (6 months vs. 4 months, p = 0.024) and PFS (8 months vs. 2.3 months, p = 0.053) were longer in chemotherapy group. The overall survival (OS) at one year was 32% in the chemotherapy group compared with 4% in the HA group (p = 0.024). Similar benefit of chemotherapy over HA was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI may offer the greatest benefit ( ORR of 68%; 1-year OS of 44%; and median OS of 18 months). Conclusion: our results suggest that intensive chemotherapy may result in a better response rate and a better overall survival compared with hypomethylating therapy in patients with morphological relapse of AML after SCT. We propose prospective studies before the use of hypomethylating agents in this setting for medically fit patients.

Disclosures

Off Label Use: Rituximab is a genetically engineered monoclonal antibody that targets a specific protein, known as CD20 found on the surface of normal and malignant B-lymphocytes.Use of Rituximab treatment for other than FDA approved indications include a rare condition of acquired factor VIII inhibitors in individuals without inherited hemophilia as an autoimmune phenomenon that may lead to life-threatening bleeding. Due to the low incidence rate of acquired inhibitors, published data consists of only case reports, and reviews.. Vij:celgene: Honoraria, Research Funding.

Topics:
allogeneic stem cell transplant, chemotherapy regimen, leukemia, myelocytic, acute, myelodysplastic syndrome, rituximab, surrogate endpoints, allopurinol, cd20 antigens, complete remission, factor viii inhibitors, acquired

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
Sign in via your Institution