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Extended Dose-Total Body Irradiation (18Gy) Followed By an Allogeneic Cell Transplantation for the Treatment of Refractory Acute Myeloid Leukemia: Early Results

Track: Poster Abstracts
Wednesday, February 26, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Mitchell Sabloff, MSc., MDCM , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Sultan Altouri, MD , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Harold Atkins, MD , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
David S Allan, MD , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Jason Tay, MD, Msc. , The University of Ottawa, Ottawa, ON, Canada
Mai Le , The Ottawa Hospital, Ottawa, ON, Canada
Linda Hamelin, APN , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Rajiv Samant, MD , The University of Ottawa, Ottawa, ON, Canada
Dawn Sheppard, BSc, MSc, MD , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Lothar B Huebsch, MD , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Tim Ramsay, MSc, PhD , The University of Ottawa, Ottawa, ON, Canada
Christopher N. Bredeson, MD, MSc , The Ottawa Hospital Blood & Marrow Transplant Program, Ottawa, ON, Canada
Introduction: Overall survival (OS) after a standard allogeneic hematopoietic cell transplantation (alloHCT) for refractory AML (rAML) is poor (<20%). Higher TBI doses have been shown to reduce AML relapse for patients in CR1. Cyclophosphamide in the conditioning is suspected of contributing to significant toxicity. Preliminary work with high doses of TBI (16Gy), without cyclophosphamide, followed by an HLA matched related or unrelated donor (MRD or MUD)-alloHCT has resulted in long-term remissions in 2 out of 4 patients. Based on these encouraging results we initiated and report on the preliminary results of a phase 2 study of single agent extended dose TBI (ED-TBI) (18Gy).

Methods: Patients (18-60 years old) with rAML and an HLA MRD or MUD received an alloHCT after ED-TBI, 2.25Gy BID (days -4 to -1) x 8 fractions (total 18Gy). Donor cells were infused on day 0. Tacrolimus (day -3) and mycophenolate mofetil (MMF) (day 1) were used for graft vs. host disease (GVHD) prophylaxis. Toxicity was measured using the CTCAE v.4 and the LENT-SOMA scales. The primary end point was treatment related mortality (TRM). Secondary endpoints included: engraftment, morbidity/mortality at 30, 100 and >180 days, incidence of GVHD, relapse rate and one year progression-free (PFS) and OS.

Results:          

Patients: Five patients have been enrolled. One patient had rAML following two induction attempts. Another patient had rAML (secondary) after one induction attempt and three had relapsed (<6 months) rAML. All had persistent leukemia at the start of ED-TBI, with 4 out of 5 having > 50% blast cells in the marrow.

Toxicity: <30 days, 2 patients had grade 3 mucositis. Two patients required parenteral feeding. One patient experienced reversible veno-occlusive disease. All patients developed diarrhea. Two patients suffered from grade 3 dehydration, requiring prolonged intravenous hydration (days 37-107).

Engraftment: Neutrophil engraftment occurred between days 15-25 and the patients were discharged from the hospital between days 19-30.

GVHD: Immunosuppression was completely tapered at day 101 in 1 patient. One patient continues to taper off at day 217, due to persistent chronic GVHD (cGVHD) and 3 did not complete tapering before relapse.  Acute GVHD occurred in 1 patient <day 30, treated with prednisone. cGVHD occurred in all patients >day 100, involving the GI tract (n=2) and liver (n=2). One patient has persistent cGVHD beyond 4 months involving the mouth and lungs.

Response: Of the 4 patients who had circulating blast cells, all were cleared by day 1. Two patients are in continuous CR on days 217 and 338. Three patients have relapsed at days 96, 110 and 139 and died on days 106, 145 and 257, respectively.

Conclusion: rAML is controlled by ED-TBI followed by an alloHCT.  The toxicity of ED-TBI is acceptable and comparable to other alloHCT conditioning regimens.  Safety and efficacy are continuing to be assessed with a goal to recruit 20 patients.

Disclosures:
M. Sabloff, Celgene, advisory committee: Advisory Board, Honoraria and Research Funding
Lundbeck, advisory committee: Advisory Board and Honoraria

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