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A Chemotherapy-Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit ATG Followed by Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants for the Treatment of Myeloid Malignancies.

A Chemotherapy-Only Regimen of Busulfan, Melphalan, and Fludarabine, and Rabbit ATG Followed by Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants for the Treatment of Myeloid Malignancies.
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Spitzer B, Jakubowski AA, Papadopoulos EB, Fuller K, Hilden PD, Young JW, Barker J, Koehne G, Perales MA, Hsu KC, van den Brink MRM, Kernan NA, Prockop SE, Scaradavou A, Castro-Malaspina H, O'Reilly RJ, Boulad F,


Spitzer B, Jakubowski AA, Papadopoulos EB, Fuller K, Hilden PD, Young JW, Barker J, Koehne G, Perales MA, Hsu KC, van den Brink MRM, Kernan NA, Prockop SE, Scaradavou A, Castro-Malaspina H, O'Reilly RJ, Boulad F, (click to view)

Spitzer B, Jakubowski AA, Papadopoulos EB, Fuller K, Hilden PD, Young JW, Barker J, Koehne G, Perales MA, Hsu KC, van den Brink MRM, Kernan NA, Prockop SE, Scaradavou A, Castro-Malaspina H, O'Reilly RJ, Boulad F,

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Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2017 07 12() pii S1083-8791(17)30573-6
Abstract

We sought to develop a myeloablative chemotherapeutic regimen to secure consistent engraftment of T-cell depleted (TCD) hematopoietic stem cell transplants (HSCT) without the need for total body irradiation, thereby reducing toxicity, while maintaining low rates of GvHD and without increasing relapse. We investigated the myeloablative combination of busulfan and melphalan, with the immunosuppressive agents fludarabine and rabbit anti-thymocyte gloubin (r-ATG) as cytoreduction prior to a T-cell depleted HSCT. No post-transplant immunosuppression was administered. Between April 2001 and May 2008, 102 patients (median age 55 years) with a diagnosis of primary or secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) underwent cytoreduction with Bu/Mel/Flu, followed by TCD grafts. T-cell depletion was accomplished by CD34(+)-selection followed by E-rosette depletion for peripheral blood stem cell grafts, and soybean agglutination followed by E-rosette depletion for bone marrow grafts. Donors included matched and mismatched, related and unrelated donors. Risk stratification was by ASBMT risk categorization for patients with primary disease. For patients with secondary/treatment-related MDS/AML, patients in complete remission (CR) 1 or refractory anemia (RA) were classified as intermediate-risk, and all other patients high-risk. Neutrophil engraftment occurred at a median of 11 days in 100/101 evaluable patients. The cumulative incidences of grade II-IV acute and chronic GvHD at 1 year were 8.8% and 5.9%, respectively. Overall- and disease-free survivals (DFS) at 5 years were 50.0% and 46.1% respectively, and the cumulative incidence of relapse and treatment related mortality were 23.5% and 28.4% respectively. Stratification by risk group demonstrated superior DFS for low-risk patients (61.5% at 5 years) compared to intermediate or high-risk (34.2, 40.0% respectively, p=0.021). For patients with AML, those in CR1 had superior 5-year DFS compared to those in ≥CR2 (60%, 30.6% respectively, p=0.01), without a significant difference in incidence of relapse (17.1%, 30.6% respectively, p=0.209). There were no differences in DFS for other patient, donor, or disease characteristics. In summary, cytoreduction with Bu/Mel/Flu and r-ATG secured consistent engraftment of TCD transplants. The incidences of acute/chronic GvHD and disease relapse were low, with favorable outcomes in this patient population with high-risk myeloid malignancies.

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