Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT


Optimal donor choice for a second allogeneic hematopoietic cell transplant (allo-HCT) in relapsed acute lymphoblastic leukemia (ALL) remains undefined. We compared outcomes using HLA-matched unrelated donors (MUD) versus haploidentical donors in this population. Primary endpoint was overall survival (OS). The MUD allo-HCT group comprised 104 patients (male = 56, 54%), median age 36 years, mostly (76%) with B-cell phenotype in complete remission (CR) (CR2/CR3 + = 76, 73%). The 61 patients (male = 38, 62%) in the haploidentical group were younger, median age 30 years (p = 0.002), had mostly (79%) a B-cell phenotype and the majority were also in CR at time of the second allo-HCT (CR2/CR3 + = 40, 66%). Peripheral blood stem cells was the most common cell source in both, but a significantly higher number in the haploidentical group received bone marrow cells (26% vs. 4%, p < 0.0001). A haploidentical donor second allo-HCT had a 1.5-fold higher 2-year OS (49% vs. 31%), albeit not statistically significant (p = 0.13). A longer time from first allo-HCT to relapse was associated with improved OS, leukemia-free survival, graft-versus-host disease-free-relapse-free survival, and lower cumulative incidences of relapse and non-relapse mortality. Results suggest no major OS difference when choosing either a MUD or haploidentical donor for ALL patients needing a second allo-HCT.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Survival outcomes.
Fig. 2: Relapse and nonrelapse mortality.


  1. 1.

    Passweg JR, Baldomero H, Basak GW, Chabannon C, Corbacioglu S, Duarte R, et al. The EBMT activity survey report 2017: a focus on allogeneic HCT for nonmalignant indications and on the use of non-HCT cell therapies. Bone Marrow Transplant 2019;

  2. 2.

    D’Souza A, Fretham C. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2018. Available at 2018.

  3. 3.

    Seibel NL Acute lymphoblastic leukemia: an historical perspective. Hematol Am Soc Hematol Educ Program 2008: 365,

  4. 4.

    Gupta V, Richards S, Rowe J. Acute Leukemia Stem Cell Transplantation Trialists’ Collaborative G. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood. 2013;121:339–50.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Pidala J, Djulbegovic B, Anasetti C, Kharfan-Dabaja M, Kumar A. Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. Cochrane Database Syst Rev. 2011;10:CD008818.

  6. 6.

    Giebel S, Marks DI, Boissel N, Baron F, Chiaretti S, Ciceri F, et al. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transpl. 2019;54:798–809.

    Article  Google Scholar 

  7. 7.

    Nagler A, Labopin M, Dholaria B, Finke J, Brecht A, Schanz U, et al. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2019;186:767–76.

  8. 8.

    Al Malki MM, Yang D, Labopin M, Afanasyev B, Angelucci E, Bashey A, et al. Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation. Blood Adv. 2020;4:2073–83.

    Article  Google Scholar 

  9. 9.

    World Medical A. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–94.

    Article  Google Scholar 

  10. 10.

    Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transpl. 2017;52:811–17.

    CAS  Article  Google Scholar 

  11. 11.

    Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transpl. 2009;15:1628–33.

    Article  Google Scholar 

  12. 12.

    Gray RJ. A class of K-sample tests for comparing the cumulative Incidence of a competing risk. Ann Stat. 1988;16:1141–54.

    Article  Google Scholar 

  13. 13.

    Hothorn T, Zeileis A. Generalized maximally selected statistics. Biometrics. 2008;64:1263–9.

    Article  Google Scholar 

  14. 14.

    Kharfan-Dabaja MA, Labopin M, Polge E, Nishihori T, Bazarbachi A, Finke J, et al. Association of second allogeneic hematopoietic cell transplant vs donor lymphocyte infusion with overall survival in patients with acute myeloid leukemia relapse. JAMA Oncol. 2018;4:1245–53.

    Article  Google Scholar 

  15. 15.

    Moukalled NM, Kharfan-Dabaja MA. What is the role of a second allogeneic hematopoietic cell transplant in relapsed acute myeloid leukemia?. Bone Marrow Transpl. 2020;55:325–31.

    Article  Google Scholar 

  16. 16.

    Orti G, Sanz J, Bermudez A, Caballero D, Martinez C, Sierra J, et al. Outcome of second allogeneic hematopoietic cell transplantation after relapse of myeloid malignancies following allogeneic hematopoietic cell transplantation: a retrospective cohort on behalf of the Grupo espanol de trasplante hematopoyetico. Biol Blood Marrow Transpl. 2016;22:584–8.

    Article  Google Scholar 

  17. 17.

    Stein AS, Kantarjian H, Gokbuget N, Bargou R, Litzow MR, Rambaldi A, et al. Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2019;25:1498–504.

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Mohamad Mohty.

Ethics declarations

Conflict of interest

MAK-D reports consultancy for Daiichi Sankyo and Pharmacyclics; JK: reports research support from Novartis, Miltenyi Biotech and Gadeta and shareholder and scientific cofounder of Gadeta; MM: Consultancy, research funding, honoraria and speaker’s bureau for Sanofi, Janssen, Amgen, Takeda, Celgene, Glaxo Smith Kline, Jazz pharmaceuticals, Adaptive, Stemline, Bristol Myers Squibb, Novartis. The remaining authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kharfan-Dabaja, M.A., Labopin, M., Bazarbachi, A. et al. Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 56, 2194–2202 (2021).

Download citation

Further reading


Quick links