Pre-Transplant Azacitidine and Allogeneic Hematopoietic Cell Transplant (HCT) Outcomes of One Hundred Fifty-Nine Patients up to Age Seventy-Five with Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

Abstract

HCT is the only known curative treatment for MDS. Treatment with the DNA methyltransferase inhibitor azacitidine (aza) has been utilized prior to HCT for tumor debulking and to slow leukemic progression. To discern the impact of aza treatment, we retrospectively analyzed the post transplant outcomes of 159 patients (pts) according to pre-HCT aza exposure. Patients included those with a diagnosis of MDS or CMML at any time point in their disease course and subsequently received a HCT. Eligible patients proceeded to HCT if they had adverse disease features such as elevated IPSS risk, treatment related MDS, progression or refractory disease. Consecutive patients receiving a HCT from July 2004 and May 2011 were evaluated. All obtained a myeloablative HCT using fludarabine and IV-busulfan [targeted to an AUC of 3500, 5300, 6000 or 7500]. GVHD prophylaxis was with tacrolimus plus either methotrexate or sirolimus or mycophenolate mofetil. Those with mismatched donors also received ATG. Seventy pts, median age of 56.5 (24.8 – 71.6) years (yrs), did not receive pre-transplant aza (NO AZA group). Forty pts were older than 55 yrs (57%). At diagnosis, IPSS risk was Low (4), Int-1 (25), Int-2 (17), High (5), not evaluable (4) (NE), AML (6) and CMML (9). Twenty-one had treatment related MDS and 15 had AML at one time. Donors included 28 match related donors (MRD), 31 matched unrelated donors (MUD) and 11 mismatched unrelated donors (mMUD). Median follow-up of surviving patients was 70.0 (29.7 – 106.6) months. Eighty-nine pts, median age of 57.8 (25.6 – 73.8) yrs, received a median of 4 (1-12) cycles of aza prior to HCT (YES AZA group). Fifty-four (61 %) were older than 55 yrs. At diagnosis, IPSS risk was Low (n=4), Int-1 (n=26), Int-2 (n=32), High (n=15), NE (n=2), AML (n=2) and CMML (n=8). Twenty-three had treatment related MDS and 11 had AML at one point. Donors included MRD (n=38), MUD (n=40) and mMUD (n=11). Median follow-up of surviving patients was 48.3 (24.1 – 103.2) months. Prior to allografting the number of marrow blasts in the No-AZA vs Yes-AZA was: <5% (n=41 vs 49), 5-10% (n=12 vs 19), 11 – 20% (n=10 vs 11), >20% (n=3 vs 4) and CMML (n=4 vs 6). All patients engrafted with no difference in engraftment rates or toxicities between the groups. At 3 years, the RFS and OS suggest improvement with preHCT AZA and approached statistical significance. Tabled 1CI NRMCI RELRFSOSNo AZA 1yr18.7 (10.5 – 28.7)38.6 (27.6 – 50.2)42.9 (31.6 – 54.5)58.6 (46.9 – 69.8) 3yrs35.7 (24.7 – 47.4)41.4 (30.2 – 53.1)24.1 (14.8 – 34.8)28.3 (18.4 – 39.4)Yes AZA 1yr18.1 (10.8 – 26.8)27.0 (18.3 – 36.6)55.1 (44.7 – 65.2)67.4 (57.4 – 76.7) 3yrs24.1 (15.7 – 33.5)33.9 (24.4 – 44.0)42.5 (32.5 – 52.9)48.0 (37.7 – 58.4)P=0.05P=0.06 Open table in a new tab Utilization of pre-HCT 5-aza is a feasible strategy and doesn’t appear to have any negative impact on HCT outcomes. Given the beneficial disease control facilitated by aza it should be offered to patients with high risk MDS being considered for a HCT.