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Nishiwaki, S.1; Mizuta, S.2; Ohashi, K.3; Fukuda, T.4; Uchida, N.5; Kanamori, H.6; Onizuka, M.7; Ozawa, Y.8; Tanaka, J.9; Ichinohe, T.10; Atsuta, Y.11; Kako, S.12

doi: 10.1097/01.HS9.0000558932.95646.b6
Poster Session I: Acute lymphoblastic leukemia - Clinical

1Department of Advanced Medicine, Nagoya University Hospital, Nagoya

2Department of Hematology & Immunology, Kanazawa Medical University, Kanazawa

3Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital

4Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital

5Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations TORANOMON HOSPITAL, Tokyo

6Department of Hematology, Kanagawa Cancer Center, Yokohama

7Department of Hematology/Oncology, Tokai University School of Medicine, Isehara

8Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya

9Department of Hematology, Tokyo Women's Medical University, Tokyo

10Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima

11Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya

12Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

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Prognostic significance of different BCR breakpoints in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) has not been established. BCR-ABL1-positive cells outside the B-lineage compartment was reported in 40% of adult patients with Ph+ALL and the frequency was different between patients with minor BCR (mi-bcr) and those with Major BCR (Ma-bcr). This could suggest the possibility of biological differences in Ph+ALL according to BCR breakpoint. In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic cell transplantation (allo-HCT) is still considered to be a choice to cure Ph+ALL. Different effect of unrelated graft source was reported on the outcome of allo-HCT with positive minimal residual disease (MRD) in a recent study.

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We aimed to clarify the impact of BCR breakpoint as well as MRD status and graft source on the outcome of allo-HCT for Ph+ALL in the era of TKI.

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We analyzed data from a registry database for 803 adult Ph+ALL patients who underwent unrelated allo-HCT in the first complete remission. BCR breakpoint was mi-bcr in 627 patients (78%), and Ma-bcr in 154 (19%).

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Overall survival (OS) rates at 4 years were 64% in mi-bcr and 61% in Ma-bcr among patients who underwent unrelated bone marrow or peripheral blood transplantation (UBMT) (P = 0.43), and 65% in mi-bcr and 67% in Ma-bcr among patients who underwent unrelated cord blood transplantation (UCBT) (P = 0.53). Similarly, the cumulative incidence of relapse or non-relapse mortality (NRM) was not significantly different between patients with mi-bcr and those with Ma-bcr in either UBMT or UCBT (Relapse: UBMT, 20% in mi-bcr and 18% in Ma-bcr at 4 years, P = 0.73; UCBT, 20% in mi-bcr and 15% in Ma-bcr at 4 years, P = 0.35; NRM: UBMT, 25% in mi-bcr and 30% in Ma-bcr at 4 years, P = 0.31; UCBT, 23% in mi-bcr and 26% in Ma-bcr at 4 years, P = 0.98). BCR breakpoint was not a significant prognostic factor in multivariate analyses, regardless of graft source. However, in subanalyses, Ma-bcr was a significant risk factor for survival and NRM in multivariate analyses among patients with MRD(+) at UBMT [Ma-bcr (vs. mi-bcr): OS: Hazard ratio (HR) 2.29, 95%CI 1.38 to 3.80, P = 0.001; NRM: HR 3.29, 95%CI 1.72 to 6.27, P < 0.001]. NRM was higher in patients with Ma-bcr than in those with mi-bcr among patients with MRD(+) at UBMT (44 % in Ma-bcr vs. 14% in mi-bcr at 4 years, P< 0.001), which led to lower survival rate in patients with Ma-bcr.

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BCR breakpoint was a significant prognostic factor in Ph+ALL patients with MRD(+) at UBMT. This is the first study reporting the possibility of significant impact of BCR breakpoint on MRD-based transplant outcome in Ph+ALL in the era of TKI.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.