The online version of this article (https://doi.org/10.1186/s13045-018-0655-8) contains supplementary material, which is available to authorized users.
Federica Giannotti, Myriam Labopin and Roni Shouval contributed equally to this work.
Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established.
This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics.
SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002).
Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.
Additional file 1: Table S1. HLA haploidentical transplantation strategy. Table S2. GvHD prophylaxis in patients receiving NTD-Haplo. Table S3. GvHD prophylaxis in patients receiving single umbilical cord blood transplantation. Table S4. Causes of Death. Table S5. The impact of MRC cytogenetic risk groups. (DOCX 19 kb)13045_2018_655_MOESM1_ESM.docx
Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P, et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008;112(9):3574–81. CrossRefPubMed
Rocha V, Wagner JE Jr, Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med. 2000;342(25):1846–54. CrossRefPubMed
Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107(8):3065–73. CrossRefPubMed
Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, et al. 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. 2013;31(10):1310–6. CrossRefPubMed
Sanz J, Boluda JC, Martin C, Gonzalez M, Ferra C, Serrano D, et al. Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transplant. 2012;47(10):1287–93. CrossRefPubMed
Ruggeri A, Sanz G, Bittencourt H, Sanz J, Rambaldi A, Volt F, et al. Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the Acute Leukemia Working Party of EBMT. Leukemia. 2014;28(4):779–86. CrossRefPubMed
Lee KH, Lee JH, Lee JH, Kim DY, Kim SH, Shin HJ, et al. Hematopoietic cell transplantation from an HLA-mismatched familial donor is feasible without ex vivo-T cell depletion after reduced-intensity conditioning with busulfan, fludarabine, and antithymocyte globulin. Biol Blood Marrow Transplant. 2009;15(1):61–72. CrossRefPubMed
Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19(1):117–22. CrossRefPubMed
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92(7):2322–33. PubMed
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81. CrossRef
Cox DR. Regression models and life-tables. In Breakthroughs in statistics. New York: Springer; 1992. p. 527–41.
Pascal L, Mohty M, Ruggeri A, Tucunduva L, Milpied N, Chevallier P, et al. Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies. Bone Marrow Transplant. 2015;50(1):45–50. CrossRefPubMed
Dumas PY, Ruggeri A, Robin M, Crotta A, Abraham J, Forcade E, et al. Incidence and risk factors of EBV reactivation after unrelated cord blood transplantation: a Eurocord and Societe Francaise de Greffe de Moelle-Therapie Cellulaire collaborative study. Bone Marrow Transplant. 2013;48(2):253–6. CrossRefPubMed
Brunstein CG, Weisdorf DJ, DeFor T, Barker JN, Tolar J, van Burik JA, et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood. 2006;108(8):2874–80. CrossRefPubMedPubMedCentral
Saraceni F, Beohou E, Labopin M, Arcese W, Bonifazi F, Stepensky P, et al. Thiotepa, busulfan and fludarabine compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia. Am J Hematol. 2018. https://doi.org/10.1002/ajh.25225. [Epub ahead of print].
Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50(Suppl 2):S37–9. CrossRefPubMed
- Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine
Josep-Maria Ribera Santasusana
Michele Angelo Carella
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II