Abstract
HCT is the only known curative treatment for MDS. Treatment with the DNA methyltransferase inhibitor 5-azacitidine (aza) can slow leukemic progression and has been utilized prior to HCT for both tumor debulking and to provide stabilization of the disease during the pre-allograft period. To discern the impact of pretransplant aza treatment on HCT outcomes, we retrospectively analyzed 132 patients (pts) according to pretransplant aza exposure. Patients included those who had a diagnosis of MDS or CMML at any time point in the course of their disease who subsequently received a HCT from a HLA-compatible donor. Eligible patients proceeded to transplant if they had adverse disease features such as elevated IPSS risk, treatment related MDS, progression of disease or refractory disease.
Consecutive patients referred for HCT between July 2004 and July 2009 were evaluated. Seventy percent of pts with an identified donor proceeded to HCT. All received a myeloablative HCT using fludarabine and IV-busulfan [targeted to a specific AUC of 3500, 5300, 6000 or 7500]. Graft versus host disease prophylaxis was with tacrolimus plus methotrexate or sirolimus or mycophenolate mofetil. Only those with mismatched donors received antithymocyte globulin.
The median age of the 64 allograft pts not receiving preHCT aza (No AZA group) was 56.8 (24.8 –73.5) years (yrs). Thirty-seven (58%) pts were older than 55 yrs. At diagnosis, IPSS risk was Low (n=4), Int-1 (n=23), Int-2 (n=13), High (n=5), not evaluable (n=4) (NE), AML (n=16) and CMML (n=9). Seventeen had treatment related MDS (tMDS) and 18 had AML at one time. Donors included 24 sibling donors (MRD), 29 matched unrelated donors (MUD) and 11 mismatched unrelated donors (mMUD). Median follow-up is 66.2 months (29.7 – 105.7 months).
Sixty-eight pts received a median of four (1-12) cycles of aza prior to HCT (YES AZA group). The median age was 57.3 (25.6 – 73.8) yrs. Thirty-nine pts (57%) were older than 55 yrs. At diagnosis, IPSS risk was Low (n=3), Int-1 (n=21), Int-2 (n=21), High (n=12), NE (n=2), AML (n=2) and CMML (n=7). Eighteen had tMDS and 10 had AML at one point. Donors included MRD (n=32), MUD (n=31) and mMUD (n=5). Median follow-up is 53.8 months (24.1 – 103.2 months).
Prior to transplant the number of marrow blasts in the No-AZA vs Yes-AZA was: <5% (n=37 vs 36), 5-10% (n=12 vs 14), 11 – 20% (n=9 vs 9), >20% (n=2 vs 3) and CMML (n=4 vs 6). All patients engrafted with no difference in engraftment rates or toxicities between the two groups. Additionally, cumulative incidence of non-relapse mortality and relapse rates at 1 yr/ 3 yrs were similar [NRM: No AZA 20.5/ 37.4% vs Yes AZA 20.7/ 23.9 %; REL: 34.2/ 37.5% vs 26.4/ 32.4%]. At 3 years, the RFS and OS suggest improvement with pretransplant AZA but do not reach statistical significance [RFS: No AZA 26% vs Yes AZA 44.1%; p = 0.14; OS: 30.9% vs 51.4%; p=0.15].
Utilization of pre-HCT 5-azaciticidine is a feasible strategy and doesn’t appear to have any negative impact on HCT outcomes. Given the disease control facilitated by aza it should be offered to patients with high risk MDS coming to transplant.
Disclosures:
Field: Celgene: Research Funding. Alsina:Millennium: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Lancet:Celgene: Research Funding. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.
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