Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil
Corresponding Author
Rita de Cássia Barbosa Tavares
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Correspondence
Rita de Cássia Barbosa Tavares, CEMO- Centro de Transplante de Medula óssea, Instituto Nacional de Cancer (INCA), Praça Cruz Vermelha 23, 7º andar, Centro, Rio de Janeiro- RJ, CEP: 20230-130, Brazil.
Email: [email protected]
Search for more papers by this authorCarmem Sales Bonfim
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorAdriana Seber
Hospital Samaritano Higienópolis, São Paulo, Brazil
Search for more papers by this authorSimone Pereira Lermontov
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Search for more papers by this authorVictor Gottardello Zecchin
Instituto de Oncologia pediátrica-GRAACC-Unifesp, São Paulo, Brazil
Search for more papers by this authorLisandro Ribeiro
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorJuliana Folloni Fernandes
Hospital Israelita Albert Einstein, São Paulo, Brazil
Instituto da Criança - Universidade de São Paulo, São Paulo, Brazil
Search for more papers by this authorLiane Esteves Daudt
Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorCarlos S. Grecco
Hospital das Clínicas da, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorLuiz Guilherme Darrigo-Jr
Hospital das Clínicas da, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorNeysimélia Villela
Hospital de Cancer de Barretos, São Paulo, Brazil
Search for more papers by this authorSamantha Nichele
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorRoseane Gouveia
Hospital Samaritano Higienópolis, São Paulo, Brazil
Search for more papers by this authorLuís Fernando Bouzas
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Search for more papers by this authorNelson Hamerschlak
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorAfonso Celso Vigorito
Universidade de Campinas, São Paulo, Brazil
Search for more papers by this authorPriscila de Oliveira da Silva
Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorCinthya Corrêa da Silva
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorCecília de Souza Fernandez
Universidade Federal Fluminense, Niterói, Brazil
Search for more papers by this authorMary Evelyn Flowers
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, USA
Search for more papers by this authorLeonardo Javier Arcuri
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorCorresponding Author
Rita de Cássia Barbosa Tavares
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Correspondence
Rita de Cássia Barbosa Tavares, CEMO- Centro de Transplante de Medula óssea, Instituto Nacional de Cancer (INCA), Praça Cruz Vermelha 23, 7º andar, Centro, Rio de Janeiro- RJ, CEP: 20230-130, Brazil.
Email: [email protected]
Search for more papers by this authorCarmem Sales Bonfim
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorAdriana Seber
Hospital Samaritano Higienópolis, São Paulo, Brazil
Search for more papers by this authorSimone Pereira Lermontov
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Search for more papers by this authorVictor Gottardello Zecchin
Instituto de Oncologia pediátrica-GRAACC-Unifesp, São Paulo, Brazil
Search for more papers by this authorLisandro Ribeiro
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorJuliana Folloni Fernandes
Hospital Israelita Albert Einstein, São Paulo, Brazil
Instituto da Criança - Universidade de São Paulo, São Paulo, Brazil
Search for more papers by this authorLiane Esteves Daudt
Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorCarlos S. Grecco
Hospital das Clínicas da, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorLuiz Guilherme Darrigo-Jr
Hospital das Clínicas da, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
Search for more papers by this authorNeysimélia Villela
Hospital de Cancer de Barretos, São Paulo, Brazil
Search for more papers by this authorSamantha Nichele
Universidade Federal do Paraná, Curitiba, Brazil
Search for more papers by this authorRoseane Gouveia
Hospital Samaritano Higienópolis, São Paulo, Brazil
Search for more papers by this authorLuís Fernando Bouzas
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Search for more papers by this authorNelson Hamerschlak
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorAfonso Celso Vigorito
Universidade de Campinas, São Paulo, Brazil
Search for more papers by this authorPriscila de Oliveira da Silva
Hospital das Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Search for more papers by this authorCinthya Corrêa da Silva
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorCecília de Souza Fernandez
Universidade Federal Fluminense, Niterói, Brazil
Search for more papers by this authorMary Evelyn Flowers
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, USA
Search for more papers by this authorLeonardo Javier Arcuri
Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
Hospital Israelita Albert Einstein, São Paulo, Brazil
Search for more papers by this authorAbstract
The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.
CONFLICT OF INTEREST
The authors have no conflict of interest to declare.
REFERENCES
- 1Eapen M, Klein JP, Ruggeri A, et al. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood. 2014; 123(1): 133-140.
- 2Eapen M, Rubinstein P, Zhang MJ, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukemia: a comparison study. Lancet. 2007; 369(9577): 1947-1954.
- 3Milano F, Gooley T, Wood B, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016; 375(10): 944-953.
- 4Cohen Y, Nagler A. Umbilical cord blood transplantation – how, when and for whom? Blood Rev. 2004; 18(3): 167-179.
- 5Barker JN, Kurtzberg J, Ballen K, et al. Optimal practices in unrelated donor cord blood transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2017; 23(6): 882-896.
- 6Alsultan A, Giller RH, Gao D, et al. GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome. Bone Marrow Transplant. 2011; 46(5): 668-675.
- 7Eapen M, Kurtzberg J, Zhang MJ, et al. Umbilical cord blood transplantation in children with acute leukemia: impact of conditioning on transplantation outcomes. Biol Blood Marrow Transplant. 2017; 23(10): 1714-1721.
- 8Lazaryan A, Weisdorf DJ, DeFor T, et al. Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biol Blood Marrow Transplant. 2016; 22(1): 134-140.
- 9Shaw PJ, Kan F, Woo Ahn K, et al. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related or matched unrelated donors. Blood. 2010; 116(19): 4007-4015.
- 10Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation. 1974; 18(4): 295-304.
- 11Filipovich AH, Weisdorf D, Pavletic S, et al. National institutes of health: consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12): 945-956.
- 12Pasquini M, Zhu X. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR summary slides, 2015. 2015. http://www.cibmtr.org. Accessed February 14, 2018.
- 13Stussi G, Seebach L, Muntwyler J, et al. Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience. Br J Haematol. 2001; 113(1): 251-253.
- 14Kudek MR, Shanley R, Zantek ND, McKenna DH, Smith AR, Miller WP. Impact of graft-recipient ABO compatibility on outcomes after umbilical cord blood transplant for nonmalignant disease. Biol Blood Marrow Transplant. 2016; 22(11): 2019-2024.
- 15Kurtzberg J, Prasad VK, Carter SL, 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(10): 4318-4327.
- 16Geyer MB, Jacobson JS, Freedman J, et al. A comparison of immune reconstitution and graft-versus-host disease following myeloablative conditioning versus reduced toxicity conditioning and umbilical cord blood transplantation in paediatric recipients: immune reconstitution and cord blood transplantation. Br J Haematol. 2011; 155(2): 218-234.
- 17Ruggeri A, Volt F, Locatelli F, et al. Unrelated cord blood transplantation for acute leukemia diagnosed in the first year of life: outcomes and risk factor analysis. Biol Blood Marrow Transplant. 2017; 23(1): 96-102.
- 18Page KM, Labopin M, Ruggeri A, et al. Factors associated with long-term risk of relapse after unrelated cord blood transplantation in children with acute lymphoblastic leukemia in remission. Biol Blood Marrow Transplant. 2017; 23(8): 1350-1358.
- 19Dumas P-Y, Ruggeri A, Robin M, et al. Incidence and risk factors of EBV reactivation after unrelated cord blood transplantation: a Eurocord and Societé Française de Greffe de Moelle-Therapie Cellulaire collaborative study. Bone Marrow Transplant. 2013; 48(2): 253-256.
- 20Politikos I, Boussiotis VA. The role of the thymus in T-cell immune reconstitution after umbilical cord blood transplantation. Blood. 2014; 124(22): 3201-3211.
- 21Walker CM, van Burik J-AH, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007; 13(9): 1106-1115.
- 22Beck JC, Wagner JE, DeFor TE, et al. Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2010; 16(2): 215-222.
- 23Granier C, Biard L, Masson E, et al. Impact of the source of hematopoietic stem cell in unrelated transplants: comparison between 10/10, 9/10-HLA matched donors and cord blood: impact of source in unrelated HSCT: 9/10-HLA donors and UCB. Am J Hematol. 2015; 90(10): 897-903.
- 24Ponce DM, Eapen M, Sparapani R, et al. In vivo T cell depletion with myeloablative regimens on outcomes after cord blood transplantation for acute lymphoblastic leukemia in children. Biol Blood Marrow Transplant. 2015; 21(12): 2173-2179.
- 25Souza MA, Passos AM, Treitinger A, Spada C. Seroprevalence of cytomegalovirus antibodies in blood donors in southern, Brazil. Rev Soc Bras Med Trop. 2010; 43(4): 359-361.
- 26Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11): 3214-3219.
- 27Piemontese S, Ciceri F, Labopin M, et al. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol. 2017; 10(1): 24.
- 28Salvatore D, Labopin M, Ruggeri A, et al. Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the acute leukemia working party of the European society for blood and marrow transplantation. Haematologica. 2018; 103(8): 1317-1328.
- 29Ringdén O, Labopin M, Ciceri F, et al. Is there a stronger graft-versus-leukemia effect using HLA-haploidentical donors compared with HLA-identical siblings? Leukemia. 2016; 30(2): 447-455.
- 30Di Stasi A, Milton DR, Poon LM, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen–matched unrelated and related donors. Biol Blood Marrow Transplant. 2014; 20(12): 1975-1981.
- 31McCurdy SR, Kasamon YL, Kanakry CG, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017; 102(2): 391-400.
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