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Unmanipulated haplo-identical donor transplantation compared with identical sibling donor had better anti-leukemia effect for refractory/relapsed acute myeloid leukemia not in remission status

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Abstract

Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.

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References

  1. Lu D-P, Dong L, Wu T, Huang X-J, Zhang M-J, Han W et al (2006) Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 107:3065–3073

    Article  CAS  Google Scholar 

  2. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Fan ZP, Wu DP, Huang XJ (2015) Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 125:3956–3962

    Article  CAS  Google Scholar 

  3. Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR (2013) T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol 31:1310–1316

    Article  CAS  Google Scholar 

  4. Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, Bacigalupo A (2014) Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant 20:1573–1579

    Article  Google Scholar 

  5. Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A et al (2015) Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia 29:1891–1900

    Article  CAS  Google Scholar 

  6. Eapen M, O’Donnell P, Brunstein CG, Wu J, Barowski K, Mendizabal A et al (2014) Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant 20:1485–1492

    Article  Google Scholar 

  7. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH, Han W, Shi HX, Huang XJ (2011) Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant 17:821–830

    Article  Google Scholar 

  8. Liu N, Ning HM, Hu LD, Jiang M, Xu C, Hu JW et al (2015) Outcome of myeloablative allogeneic peripheral blood hematopoietic stem cell transplantation for refractory/relapsed AML patients in NR status. Leuk Res 39:1375–1381

    Article  Google Scholar 

  9. Duléry R, Ménard AL, Chantepie S, El-Cheikh J, François S, Delage J et al (2018) Sequential conditioning with thiotepa in T cell- replete hematopoietic stem cell transplantation for the treatment of refractory hematologic malignancies: comparison with matched related, Haplo-mismatched, and unrelated donors. Biol Blood Marrow Transplant 24:1013–1021

    Article  Google Scholar 

  10. Gu B, Zhang X, Chen G, Wu X, Ma X, Chen S, Wu D (2018) Efficacy of haploidentical hematopoietic stem cell transplantation compared to HLA-matched transplantation for primary refractory acute myeloid leukemia. Ann Hematol 97:2185–2194

    Article  CAS  Google Scholar 

  11. Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28:3730–3738

    Article  Google Scholar 

  12. Craddock C, Labopin M, Pillai S, Finke J, Bunjes D, Greinix H, Ehninger G, Steckel NK, Zander AR, Schwerdtfeger R, Buchholz S, Kolb HJ, Volin L, Fauser A, Polge E, Schmid C, Mohty M, Rocha V (2011) Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukaemia. Leukemia 25:808–813

    Article  CAS  Google Scholar 

  13. Mrózek K, Heerema NA, Bloomfield CD (2004) Cytogenetics in acute leukemia. Blood Rev 18:115–136

    Article  Google Scholar 

  14. Kanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, Karasuno T et al (2003) Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991–2000). Blood 102:1541–1547

    Article  CAS  Google Scholar 

  15. Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH et al (1997) Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol 15:1767–1777

    Article  CAS  Google Scholar 

  16. Chang YJ, Wang Y, Liu YR, Xu LP, Zhang XH, Chen H et al (2017) Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol 10:1–13

    Article  Google Scholar 

  17. Barrett AJ, Battiwalla M (2010) Relapse after allogeneic stem cell transplantation. Expert Rev Hematol 3:429–441

    Article  Google Scholar 

  18. Wang Y, Liu DH, Fan ZP, Sun J, Wu XJ, Ma X, Xu LP, Liu KY, Liu QF, Wu DP, Huang XJ (2012) Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study. Clin Transpl 26:635–643

    Article  Google Scholar 

  19. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Zhang XH, Chen YH, Han W, Wang FR, Wang JZ, Yan CH, Huang XJ (2012) Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis. Bone Marrow Transplant 47:1099–1104

    Article  CAS  Google Scholar 

  20. Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F, Grasso R, Zupo S, Raiola AM, Gobbi M, Frassoni F, Bacigalupo A (2007) Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia [2]. Blood 109:5063–5064

    Article  CAS  Google Scholar 

  21. Jackson G, Taylor P, Smith GM, Marcus R, Smith A, Chu P, Littlewood TJ, Duncombe A, Hutchinson M, Mehta AB, Johnson SA, Carey P, Mackie MJ, Ganly PS, Turner GE, Deane M, Schey S, Brookes J, Tollerfield SM, Wilson MP (2001) A multicentre, open, non-comparative phase II study of a combination of fludarabine, cytarabine and G-CSF in relapsed and refractory AML and de novo RAEB-MDS. Br J Haematol 112:127–137

    Article  CAS  Google Scholar 

  22. Sierra J, Storer B, Hansen JA, Bjerke JW, Martin PJ, Petersdorf EW, Appelbaum FR, Bryant E, Chauncey TR, Sale G, Sanders JE, Storb R, Sullivan KM, Anasetti C (1997) Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood 89:4226–4235

    Article  CAS  Google Scholar 

  23. Ferguson P, Hills RK, Grech A, Betteridge S, Kjeldsen L, Dennis M, Vyas P, Goldstone AH, Milligan D, Clark RE, Russell NH, Craddock C, UK NCRI AML Working Group (2016) An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation. Haematologica 101:1351–1358

    Article  CAS  Google Scholar 

  24. Pfrepper C, Klink A, Behre G, Schenk T, Franke GN, Jentzsch M, Schwind S, al-Ali HK, Hochhaus A, Niederwieser D, Sayer HG (2016) Risk factors for outcome in refractory acute myeloid leukemia patients treated with a combination of fludarabine, cytarabine, and amsacrine followed by a reduced-intensity conditioning and allogeneic stem cell transplantation. J Cancer Res Clin Oncol 142:317–324

    Article  CAS  Google Scholar 

  25. Zhang C, Chen X, Mb JL, Gao L, Liu Y, Gao L et al (2015) Decitabine as a conditioning regimen in haploidentical stem cell transplantation for refractory acute myeloid leukaemia. J Clin Pharm Ther 40(3):336–338

    Article  CAS  Google Scholar 

  26. Hong M, Wu Q, Hu C, Fang J, You Y, Zhong Z, Zou P, Hu Y, Xia L (2012 Feb) Idarubicin-intensified BUCY2 regimens may lower relapse rate and improve survival in patients undergoing allo-SCT for high-risk hematological malignancies : a retrospective analysis. Bone Marrow Transplant 47(2):196–202

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, China Si Pu Lan Road, Yanjiao Development Zone, Langfang, 065201, Hebei, China

    Yue Lu, Yan-Li Zhao, Jian-Ping Zhang, Min Xiong, Xing-Yu Cao, De-Yan Liu, Rui-Juan Sun, Zhi-Jie Wei, Jia-Rui Zhou & Dao-Pei Lu

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  1. Yue Lu
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  2. Yan-Li Zhao
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  3. Jian-Ping Zhang
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Highlights

• The anti-leukemia effect could be improved among R/R AML patients in NR status undergoing an allo-HSCT by using a haplo-identical donor SCT compared with an identical sibling donor SCT.

• Pre-transplantation adverse factors can delineate subgroups of R/R AML patients in NR status that could derive maximal benefit from HSCT.

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Lu, Y., Zhao, YL., Zhang, JP. et al. Unmanipulated haplo-identical donor transplantation compared with identical sibling donor had better anti-leukemia effect for refractory/relapsed acute myeloid leukemia not in remission status. Ann Hematol 99, 2911–2925 (2020). https://doi.org/10.1007/s00277-020-04283-0

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