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Long-term outcome and prognostic factors of unrelated cord blood transplantation in children with haematological malignancies: a retrospective study using the Spanish Working Party for BMT in Children (GETMON) database

Bone Marrow Transplantation volume 49, pages 767–772 (2014)Cite this article

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Abstract

Outcomes of unrelated cord blood transplants (UCBT) were assessed in 172 consecutive children, median age 5 years (range: 0.5–18), with haematological malignancies treated at nine Spanish hospitals between February 1996 and April 2009. Data were collected from the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) database. ALL was diagnosed in 125 patients, AML in 43 and myelodysplastic syndrome in 4. Myeloid engraftment (ANC⩾0.5 × 109/L) occurred in 87.2% at a median of 22 days and was associated with the total nucleated cell (TNC) dose infused and use of a TT-containing conditioning regimen. Cumulative incidence of relapse was 20% at 1 year post transplant and 29% at 3 years, being higher in patients with a diagnosis of ALL, very high risk disease and GVHD grades 0–1. Cumulative incidence of non-relapse mortality (NRM) was 19% at 100 days post transplant and 39% at 1 year. BU-FLU-TT-ATG-conditioned patients had lower NRM. Disease-free survival (DFS) was 40% at 2 years post transplant (for patients transplanted since 2006). On multivariate analysis, TNC dose infused, AML and BU-FLU-TT-ATG-conditioning regimen increased the probability of DFS. It is of paramount importance to select cord blood units with the highest cell dose. As the BU-FLU-TT-ATG-conditioning regimen was associated with better DFS owing to lower NRM, further prospective studies testing this regimen are warranted.

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References

  1. Gluckman E, Ruggeri A, Volt F, Cunha R, Boudjedir K, Rocha V . Milestones in umbilical cord blood transplantation. Br J Haematol 2011; 154: 441–447.

    Article  PubMed  Google Scholar 

  2. Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.

    CAS  PubMed  Google Scholar 

  3. Rocha V, Kabbara N, Ionescu I, Ruggeri A, Purtill D, Gluckman E . Pediatric related and unrelated cord blood transplantation for malignant diseases. Bone Marrow Transplant 2009; 44: 653–659.

    Article  CAS  PubMed  Google Scholar 

  4. Smith AR, Wagner JE . Alternative hematopoietic stem cell sources for transplantation: Place of umbilical cord blood. Br J Haematol 2009; 147: 246–261.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Sanz J, Boluda JCH, Martín C, González M, Ferrá 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: 1287–1293.

    Article  CAS  PubMed  Google Scholar 

  6. Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.

    CAS  PubMed  Google Scholar 

  7. Iori AP, Arcese W, Milano F, Calabrese E, Torelli GF, Barberi W et al. Unrelated cord blood transplant in children with high-risk acute lymphoblastic leukemia: a long-term follow-up. Haematologica 2007; 92: 1051–1058.

    Article  PubMed  Google Scholar 

  8. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.

    Article  CAS  PubMed  Google Scholar 

  9. Ohnuma K, Isoyama K, Ikuta K, Toyoda Y, Nakamura J, Nakajima F et al. Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies. Br J Haematol 2001; 112: 981–987.

    Article  CAS  PubMed  Google Scholar 

  10. Bertaina A, Bernardo MA, Caniglia A, Vinti L, Giorgiani G, Locatelli F . Cord blood transplantation in children with heamatological malignancies. Best Pract Res Clin Haematol 2010; 23: 189–196.

    Article  PubMed  Google Scholar 

  11. Díaz MA, Gonzalez-Vicent M, Ramirez M, Sevilla J, Lassaletta A, Perez A et al. Allogenic cord blood transplantation in children with hematological malignancies: A long-term follow-up single-center study. Pediatr Hematol Oncol 2009; 26: 165–174.

    Article  PubMed  Google Scholar 

  12. Wang J, Zhan P, Ouyang J, Chen B, Zhou R, Yang R . Unrelated donor umbilical cord blood transplantation versus unrelated bone marrow transplantation in adult and paediatric patients: A meta-analysis. Leuk Res 2010; 34: 1018–1022.

    Article  PubMed  Google Scholar 

  13. Kurtzberg J, Prasad VK, Carter SL, Wagner JE, Baxter-Lowe LA, Wall D et al. Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 2008; 112: 4318–4327.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Madureira AB, Eapen M, Locatelli F, Teira P, Zhang MJ, Davies SM et al. Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation. Leukemia 2011; 25: 449–454.

    Article  CAS  PubMed  Google Scholar 

  15. Ciurea SO, Saliba RM, Hamerschlak N, Karduss AA, Bassett R, Fernández VM et al. Fludarabine, melphalan, thitepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Leukemia &Lymphoma 2012; 53: 901–906.

    Article  CAS  Google Scholar 

  16. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  17. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  18. Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.

    Article  CAS  PubMed  Google Scholar 

  19. Hwang WY, Samuel M, Tan D, Koh LP, Lim W, Linn YC . A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant 2007; 13: 444–453.

    Article  PubMed  Google Scholar 

  20. Shi-Xia X, Xian-Hua T, Xiang-Feng T . Unrelated umbilical cord blood transplantation and unrelated bone marrow transplantation in children with hematological disease: a meta-analysis. Pediatr Transplant 2009; 13: 278–284.

    Article  PubMed  Google Scholar 

  21. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  PubMed  Google Scholar 

  22. Zhang MJ, Davies SM, Camitta BM, Logan B, Tiedemann K, Eapen M et al. Comparison of outcomes after HLA-sibling and unrelated donor transplantation for children with high-risk acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2012; 18: 1204–1210.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Stevens CE, Carrier C, Carpenter C, Sung D, Scaradavou A. . HLA. mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood selection. Blood 2011; 118: 3969–3978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Takanashi M, Atsuta Y, Fujiwara K, Kodo H, Kai S, Sato H et al. The impact of anti-HLA antibodies on unrelated cord blood transplantations. Blood 2010; 116: 2839–2846.

    Article  CAS  PubMed  Google Scholar 

  25. Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, Bernstein ID . Notchmediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 2010; 16: 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. New Engl J Med 2012; 367: 2305–2315.

    Article  CAS  PubMed  Google Scholar 

  27. Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693–4699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bautista G, Cabreza JR, Regidor C, Forés R, García-Marco JA, Ojeda E et al. Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third party donor. Bone Marrow Transplant 2009; 43: 365–373.

    Article  CAS  PubMed  Google Scholar 

  29. Frassoni F, Gualandi F, Podesta M, Raiola AM, Ibatici A, Piaggio G et al. Direct intrabone transplant of unrelated cordblood cells in acute leukaemia: a phase I/II study. Lancet Oncol 2008; 9: 831–839.

    Article  CAS  PubMed  Google Scholar 

  30. Bernardo ME, Piras E, Vacca A, Giorgiani G, Zecca M, Bertaina A et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood 2012; 120: 473–476.

    CAS  PubMed  Google Scholar 

  31. Li C, Wu X, Feng X, He Y, Liu H, Pei F et al. A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation. Blood 2012; 120: 3875–3881.

    Article  CAS  PubMed  Google Scholar 

  32. Ciurea SO, Saliba RM, Hamerschlak N, Karduss Aurueta AJ, Bassett R et al. Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Leuk Lymphoma 2012; 53: 901–906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sanz J, Sanz MA, Saavedra S, Lorenzo I, Montesinos P, Senent L et al. Cord blood transplantation from unrelated donors in adults with high risk acute myelogenous leukemia. Biol Blood Marrow Transplant 2010; 16: 86–89.

    Article  PubMed  Google Scholar 

  34. Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A et al. A novel reduced-intensity conditioning regimen for unrelated umbilñical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant 2014; 20: 326–336.

    Article  PubMed  Google Scholar 

  35. 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: 779–786.

    Article  CAS  PubMed  Google Scholar 

  36. Barker JN, Scaradavou A, Stevens CE . Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies. Blood 2010; 115: 1843–1849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.

    Article  CAS  PubMed  Google Scholar 

  38. Chiesa R, Gilmour K, Qasim W, Adams S, Woth A JJ, Zhan H et al. Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol 2012; 156: 656–666.

    Article  CAS  PubMed  Google Scholar 

  39. Wachowiak J, Sykora KW, Cornissh J, Chybicka A, Kowalcyk JR, Gorczyńska E et al. Treosulfan-based preparative regimens for allo-HSCT in childhood haematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party. Bone Marrow Transplant 2011; 46: 1510–1518.

    Article  CAS  PubMed  Google Scholar 

  40. Atsuta Y, Kanda J, Takanashi M, Morishima Y, Taniguchi S, Takahashi S et al. Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia. Haematologica 2013; 98: 814–822.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rocha V, Spellman S, Zhang MJ, Ruggeri A, Purtill D, Brady C et al. Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for haematologic malignancy. Biol Blood Marrow Transplant 2012; 18: 1890–1896.

    Article  PubMed  Google Scholar 

  42. Eapen M, Klein JP, Sanz JF, Spellman S, Ruggeri A, Anasetti C et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol 2011; 12: 1214–1221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Santiago Perez Hoyos for statistical analyses, Marta Pulido, MD, for manuscript editing and editorial assistance and Christine O’Hara for the English revision.

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Authors and Affiliations

  1. Servicio de Oncología y Hematología Pediátricas, Hospital Universitario Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain

    C Díaz de Heredia, I Elorza, T Olivé & J Sánchez de Toledo

  2. Unidad de Trasplante, Hospital Niño Jesús, Universidad Autónoma de Madrid, Madrid, Spain

    M González & M A Díaz

  3. Unidad de Oncología y TPH Pediátrico, Hospital Universitario Politécnico La Fe, Universidad de Valencia, Valencia, Spain

    A Verdeguer & J M Fernández

  4. Servicio de Hematología, Unidad de Hematología Infantil, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain

    A Rodriguez

  5. Unidad de Hematología y Oncología Infantil, Hospital la Paz, Universidad Autónoma de Madrid, Madrid, Spain

    A Martinez

  6. Servicio de Hematología, Hospital Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain

    J M Pérez

  7. Unidad Pediátrica de Hematología, Oncología y TPH, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

    I Badell

  8. Servicio de Hematología, Hospital Universitario Regional Carlos Haya, Universidad de Málaga, Málaga, Spain

    M E Gonzalez

  9. Unidad de Hematología Pediátrica, Servicio de Pediatría, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain

    M S Maldonado

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  1. C Díaz de Heredia
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Correspondence to C Díaz de Heredia.

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Díaz de Heredia, C., González, M., Verdeguer, A. et al. Long-term outcome and prognostic factors of unrelated cord blood transplantation in children with haematological malignancies: a retrospective study using the Spanish Working Party for BMT in Children (GETMON) database. Bone Marrow Transplant 49, 767–772 (2014). https://doi.org/10.1038/bmt.2014.30

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