Maintenance Hypomethylating Therapy Post Allogeneic Stem Cell Transplantation Provides Favorable Progression Free Survival in High Risk Acute Myelogenous Leukemia or Non Responsive Myelodysplastic Syndrome

Introduction

Patients with acute myelogenous leukemia (AML) or non responsive myelodysplastic syndrome (MDS) who fail to achieve a complete remission, have unfavorable cytogenetics or are refractory to therapy have a poor prognosis.  Allogeneic HSCT is frequently considered a salvage option for these patients although remissions are short-lived.  New strategies are needed for maintaining remission in this extremely high risk patient group.  We hypothesized hypomethylating agents post allogeneic HSCT would enable patients to remain in complete remission.

Methods

Eleven patients were treated.  Patient characteristics: median age, 48 years (range, 18-70 years), PBSC (n=9) or bone marrow (n=2); Diagnoses AML= 10, Non- responsive MDS=1, CIBMTR disease risk category: High [n=8], Intermediate [n=1], Low [n=2]; 36% of the patients had primary induction failure, 54% had complex molecular abnormalities with 18% of the patients having deletion 11q 23 molecular abnormalities.  Donors were unrelated (36%) and related (64%). All but 1 donor-recipient pairs were fully matched.  Preparative regimen- busulfan based (16mg/kg or equivalent) (82%), TBI ≥ 12 Gy (9%) based or reduced-intensity haplo-identical regimen (9%).  The median number of prior chemotherapy regimens was 2.5 (range, 2-6).  Azacitidine (n=10) or decitabine (n=1) was selected at physician discretion as a planned prophylactic regimen post allogeneic HSCT engraftment.  Initial starting doses were based on hematological conditions at the time of therapy initiation.

Results

Ten patients received azacitidine subcutaneously daily for seven days for a median of 5 cycles (range, 1-10 cycles) and one patient received decitabine 20mg/m² intravenously for 5 days for 3 cycles. Median initial Azacitidine dose of 50 mg/m² (range, 25-75 mg/m²) were given at a median of 40 days (range, 38-101 days) post HSCT engraftment. Azacitidine doses were increased based on counts to a maximum dose of 75mg/m².  With a median follow-up of 24 months (range, 1.7-49 months) 6 patients are alive in complete remission.  Twenty-four month progression free survival is 51% with overall survival of 76%. 

Conclusion

Given the dismal results of progression free survival and overall survival following allogeneic HSCT in high risk AML or non responsive MDS, hypomethylating agents given post transplantation provide a valuable approach to prolonging remission.