Impact of MRD on clinical outcomes of unrelated hematopoietic stem cell transplantation in patients with Ph+ALL: A retrospective nationwide study

Author:

Hirabayashi Shigeki1ORCID,Kondo Tadakazu1ORCID,Nishiwaki Satoshi2,Mizuta Shuichi3,Doki Noriko4,Fukuda Takahiro5,Uchida Naoyuki6ORCID,Ozawa Yukiyasu7,Kanda Yoshinobu8ORCID,Imanaka Ryota9,Takahashi Satoshi10,Ishikawa Jun11,Yano Shingo12,Nakamae Hirohisa13,Eto Tetsuya14,Kimura Takafumi15,Tanaka Junji16,Ichinohe Tatsuo17,Atsuta Yoshiko1819,Kako Shinichi8ORCID

Affiliation:

1. Department of Hematology and Oncology, Graduate School of Medicine Kyoto University Kyoto Japan

2. Department of Advanced Medicine Nagoya University Hospital Nagoya Japan

3. Department of Hematology & Immunology Kanazawa Medical University Kanazawa Japan

4. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan

5. Department of Hematopoietic Stem Cell Transplantation National Cancer Center Hospital Tokyo Japan

6. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital Tokyo Japan

7. Department of Hematology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Nagoya Japan

8. Division of Hematology Jichi Medical University Saitama Medical Center Saitama Japan

9. Department of Hematology Hiroshima Red Cross Hospital & Atomic‐Bomb Survivors Hospital Hiroshima Japan

10. Department of Hematology/Oncology, The Institute of Medical Science The University of Tokyo Tokyo Japan

11. Department of Hematology Osaka International Cancer Institute Osaka Japan

12. Clinical Oncology and Hematology The Jikei University School of Medicine Tokyo Japan

13. Department of Hematology Osaka Metropolitan University Hospital Osaka Japan

14. Department of Hematology Hamanomachi Hospital Fukuoka Japan

15. Preparation Department Japanese Red Cross Kinki Block Blood Center Osaka Japan

16. Department of Hematology Tokyo Women's Medical University Tokyo Japan

17. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan

18. Japanese Data Center for Hematopoietic Cell Transplantation Nagakute Japan

19. Department of Registry Science for Transplant and Cellular Therapy Aichi Medical University School of Medicine Nagakute Japan

Abstract

AbstractMeasurable residual disease (MRD) status before transplantation has been shown to be a strong prognostic factor in patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL). However, the outcomes of unrelated hematopoietic stem cell transplantation based on the MRD status have not been fully investigated. In this retrospective study, we compared the outcomes of 715 consecutive adults with Ph+ ALL in complete remission who underwent unrelated cord blood transplantation (UCBT) (single‐unit UCBT, n = 232 [4/6, 5/6, and 6/6 HLA match]), HLA‐matched unrelated bone marrow transplantation (UBMT; n = 292 [8/8 HLA match]), or HLA‐mismatched UBMT (n = 191 [7/8 HLA match]). In the MRD+ cohort, adjusted 3‐year leukemia‐free survival rates were 59.8%, 38.3%, and 55.5% after UCBT, HLA‐matched UBMT, and HLA‐mismatched UBMT, respectively. In the MRD cohort, the corresponding rates were 65.3%, 70.4%, and 69.7%, respectively. The MRD+ HLA‐matched UBMT group had a significantly higher risk of relapse than the MRD+ HLA‐mismatched UBMT group (hazard ratio [HR] in the MRD+ HLA‐mismatched UBMT group, 0.33; 95% confidence interval [CI] 0.15–0.74) and the MRD+ UCBT group (HR in the MRD+ UCBT group, 0.38; 95% CI 0.18–0.83). Furthermore, HLA‐matched UBMT had a significant effect of MRD on death (HR 1.87; 95% CI 1.19–2.94), relapse or death (HR 2.24; 95% CI 1.50–3.34), and relapse (HR 3.12; 95% CI 1.75–5.57), while UCBT and HLA‐mismatched UBMT did not. In conclusion, our data indicate Ph+ ALL patients with positive MRD may benefit from undergoing UCBT or HLA‐mismatched UBMT instead of HLA‐matched UBMT to reduce leukemic relapse.

Funder

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Wiley

Subject

Hematology

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