Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Therapies, MPN, Myeloid Malignancies, transplantation
Methods: Regardless of donor source, all patients were conditioned with our institution’s two-step approach. After reduced intensity conditioning consisting of fludarabine, 2 Gy total body irradiation, thiotepa (n=3) OR busulfan (n=8), and in 1 case myeloablative conditioning with 12 Gy total body irradiation, patients received an unmanipulated donor lymphocyte product (DLI) containing 2 x 108/kg CD3+ cells. After 2 days, cyclophosphamide (CY) 60 mg/kg was administered daily x 2 for bidirectional T cell tolerization. One day after CY completion, a CD34-selected stem cell product was infused. All patients received mycophenolate mofetil and tacrolimus beginning on d-1. Pre-conditioning splenic radiation was added starting in 2017 to decrease splenic sequestration of donor cells. This change affected the last six patients in the analysis.
Results: Six patients had primary MF and six patients had secondary MF. Donor source was a HLA matched (n=5, median age 54y, range 44-65) or haploidentical (n=7, median age 66y, range 47-67) relative. Eight patients received pre-HSCT radiation or splenectomy. Outcome data is summarized in the table. Median follow-up is 29 (range 6-95.6) months. Median time to neutrophil and platelet engraftment was 12 (range 9-13) days and 19 (13-40) days respectively. Patients undergoing pre-HSCT splenic therapy recovered platelets more rapidly than those without, median 19 vs 27 days, (p=0.059). All patients ultimately achieved 100% donor chimerism. While there was a trend in the M-HSCT group for higher donor T cell chimerism at d+28 in patients undergoing pre-HSCT splenic therapy, (p=0.083), donor source had the most significant impact on the pace of donor chimerism recovery. All 4 DLIs given in this group for fluctuating donor T cell chimerism occurred in M-HSCT recipients. At d+28 median donor T cell chimerism was 100% (range 91-100) in HI-HSCT versus 92% (range 67-100%) in M-HSCT recipients, (p=0.037). Probability of OS at 3 years was 90%. No patient receiving splenic therapy experienced disease progression. Two patients who received DLI experienced graft versus host disease (GVHD), grade 3 acute GVHD in one and extensive chronic GVHD in the other.
Conclusion: HSCT using the two-step approach is associated with rapid engraftment and excellent survival in patients with MF. Pre-HSCT splenic therapy was associated with more rapid platelet recovery. Unlike HI-HSCT, M-HSCT patients receiving RIC conditioning experienced initial fluctuating donor T-cell chimerism, a finding worth further exploration in larger trials.
Disclosures: Gergis: Jazz: Other: Ad board, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Kite: Speakers Bureau; Mesoblast: Other: Ad Board; Incyte: Speakers Bureau; Merck: Speakers Bureau. Flomenberg: Tevogen: Consultancy, Honoraria.
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