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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)

Track: Poster Abstracts
Saturday, March 1, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Teresa Field, MD PhD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Janelle Perkins, PharmD , BMT, Moffitt Cancer Center, Tampa, FL
Ryan Hillgruber , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Taiga Nishihori, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Marcie Riches, MD, MS , H. Lee Moffitt Cancer Center, Tampa, FL
Asmita Mishra, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Joseph Pidala, MD, MS , H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Frederick Locke , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Lia Elena Perez, M.D. , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Brian Betts, MD , BMT, H. Lee Moffitt Cancer Institute, Tampa, FL
Ernesto Ayala , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Melissa Alsina, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Jose-Leonel Ochoa, MD , BMT, H. Lee Moffitt Cancer Center, Tampa, FL
Eric Padron, MD , Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
Jeffery Lancet, MD , Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
Hugo Fernandez, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Alan F. List, MD , Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Rami Komrokji , Hematology, H. Lee Moffitt Cancer Center, Tampa, FL
Mohamed Kharfan-Dabaja , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center, Tampa, FL
Claudio Anasetti, MD , Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
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.

 

 

CI NRM

CI REL

RFS

OS

No AZA 

 

 

 

 

              1yr

18.7

(10.5 – 28.7)

 

38.6

(27.6 – 50.2)

 

42.9

(31.6 – 54.5)

 

58.6

(46.9 – 69.8)

 

              3yrs

35.7

(24.7 – 47.4)

 

41.4

(30.2 – 53.1)

 

24.1

(14.8 – 34.8)

 

28.3

(18.4 – 39.4)

 

Yes AZA 

 

 

 

 

              1yr

18.1

(10.8 – 26.8)

 

27.0

(18.3 – 36.6)

 

55.1

(44.7 – 65.2)

 

67.4

(57.4 – 76.7)

 

              3yrs               

24.1

(15.7 – 33.5)

 

33.9

(24.4 – 44.0)

 

42.5

(32.5 – 52.9)

 

48.0

(37.7 – 58.4)

 

 

 

 

P=0.05

P=0.06

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.

Disclosures:
T. Field, Celgene, None: Research Funding

M. Alsina, Millennium, Investigator and consultant: Consultancy and Research Funding

J. Lancet, Celgene, Research & Consultant: Consultancy and Research Funding

A. F. List, Celgene, None: DSMC on a trial

R. Komrokji, Celgene, None: Honoraria and Research Funding

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