Abstract
We undertook a retrospective study using the national registry data of hematopoietic stem cell transplantation (HSCT) in Japan to investigate the effect of graft source, particularly autologous or allogeneic tissue, on the treatment outcome in patients aged less than 18 years with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Survival analysis was conducted on 31 autologous HSCT (auto-HSCT) and 48 allogeneic HSCT (allo-HSCT) recipients between 1990 and 2013. The 5-year survival rates were significantly lower for allo-HSCT compared to auto-HSCT recipients (32% vs. 55%; P = 0.036). Multivariate analysis of survival rates identified allogeneic graft, Burkitt histology, and lack of response to chemotherapy as poor prognostic factors for survival. The cumulative incidence of treatment-related mortality (TRM) was significantly higher in allo-HSCT compared to auto-HSCT recipients (P = 0.017), explaining the difference in survival rates. In patients with Burkitt lymphoma (BL), overall survival was significantly inferior in the group of patients undergoing HSCT within 12 months from the initial diagnosis (P = 0.039). These data indicate that treatment outcomes for HSCT in children and adolescents with B-NHL were better in autograft recipients, suggesting that greater attention should be paid to the risk of TRM, especially after allografts, for patients with BL.
Similar content being viewed by others
References
Minard-Colin V, Brugières L, Reiter A, Cairo MS, Gross TG, Woessmann W, et al. Non-Hodgkin lymphoma in children and adolescents: progress through effective collaboration, current knowledge, and challenges ahead. J Clin Oncol. 2015;33:2963–74.
Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmerman M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin–Frankfurt–Munster Group Trial NHL-BFM 90. Blood. 1999;94:3294–306.
Patte C, Auperin A, Michon J, Behrendt H, Leverger G, Frappaz D, et al. The Societe Francaise d’Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphoma and L3 leukemia. Blood. 2001;97:3370–9.
Bradley MB, Cairo MS. Stem cell transplantation for pediatric lymphoma: past, present and future. Bone Marrow Transplant. 2008;41:149–58.
Fujita N, Mori T, Mitsui T, Inada H, Horibe K, Tsurusawa M. The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia: a retrospective analysis of enrolled cases in Japan. Pediatr Blood Cancer. 2008;51:188–92.
Bureo E, Ortega JJ, Muñoz A, Cubells J, Madero L, Verdaguer A, et al. Bone marrow transplantation in 46 pediatric patients with non-Hodgkin’s lymphoma. Bone Marrow Transplant. 1995;15:353–9.
Giulino-Roth L, Ricafort R, Kernan NA, Small TN, Tripett TM, Steinherz PG, et al. Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation. Pediatr Blood Cancer. 2013;60:2018–24.
Jourdain A, Auperin A, Minard-Colin V, Aladjidi N, Zsiros J, Coze C, et al. Outcome and prognostic factors of relapse in children and adolescents with mature B-cell lymphoma and leukaemia treated in 3 consecutive prospective lymphomes malins B protocols. Study of the Societe Francaise des Cancers de l’Enfant. Haematologica. 2015;100:810–7.
Gross TG, Hale GA, He W, Camitta BM, Sanders JE, Cairo MS, et al. Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. Biol Blood Marrow Transplant. 2010;16:223–30.
Okur FV, Krance R. Stem cell transplantation in childhood non-Hodgkin’s lymphoma. Curr Hematol Malig Rep. 2010;5:192–9.
Levine JE, Harris RE, Loberiza FR Jr, Armitage JO, Vose JM, Besien KV, et al. A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma. Blood. 2003;101:2476–82.
Mitsui T, Mori T, Fujita N, Inada H, Horibe K, Tsurusawa M. Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan. Pediatr Blood Cancer. 2009;52:591–5.
Woessmann W, Peters C, Lenhard M, Burkhardt B, Sykora KW, Dilloo D, et al. Allogeneic hematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents: a Berlin–Frankfurt–Munster group report. Br J Haematol. 2006;133:176–82.
Peniket AJ, Ruiz de Elvira MC, Taghipour G, Cordonnier C, Gluckman E, de Witte T, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003;31:667–78.
Maramattom LV, Hari PN, Burns LJ, Carreras J, Arcese W, Cairo MS, et al. Autologous and allogeneic transplantation for Burkitt lymphoma outcomes and changes in utilization: a report from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2013;19:173–9.
Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP system. Int J Hematol. 2007;86:269–74.
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.
Osumi T, Mori T, Fujita N, Saito AM, Nakazawa A, Tsurusawa M, et al. Relapsed/refractory pediatric B-cell non-Hodgkin lymphoma treated with rituximab combination therapy: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. Pediatr Blood Cancer. 2016;63:1794–9.
Anoop P, Sankpal S, Stiller C, Tewari S, Lancaster DL, Khabra K, et al. Outcome of childhood relapsed or refractory mature B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia. Leuk Lymphoma. 2012;53:1882–8.
Kim H, Park ES, Lee SH, Koo HH, Kim HS, Lyu CJ, et al. Clinical outcome of relapsed or refractory Burkitt lymphoma and mature B-cell lymphoblastic leukemia in children and adolescents. Cancer Res Treat. 2014;46:358–65.
Ladenstein R, Pearce R, Hartmann O, Patte C, Goldstone T, Philip T. High-dose chemotherapy with autologous bone marrow rescue in children with poor-risk Burkitt’s lymphoma: a report from the European lymphoma bone marrow transplantation registry. Blood. 1997;90:2921–30.
Jones RJ, Ambinder RF, Piantadosi S, Stantos GW. Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood. 1991;77:649–53.
Kobayashi R, Mitsui T, Fujita N, Osumi T, Aoki T, Aoki K, Suzuki R, Fukuda T, Miyamoto T, Kato K, Nakamae H, Goto H, Eto T, Inoue M, Mori T, Terui K, Onizuka M, Koh K, Koga Y, Ichinohe T, Sawada A, Atsuta Y, Suzumiya J (2017) Outcome differences between children and adolescents and young adults with non-Hodgkin lymphoma following stem cell transplantation. Int J Hematol 105(3):369–376
Rosenwald A, Ott G. Burkitt lymphoma versus diffuse large B-cell lymphoma. Ann Oncol. 2008;19:67–9.
Reiter A, Klapper W. Recent advances in the understanding and management of diffuse large B-cell lymphoma in children. Br J Haematol. 2008;142:329–47.
Fujita N, Kobayashi R, Takimoto T, Nakagawa A, Ueda K, Horibe K. Results of the Japan Association of Childhood Leukemia Study (JACLS) NHL-98 protocol for the treatment of B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia in childhood. Leuk Lymphoma. 2011;52:223–9.
Cairo MS, Woessmann W, Pagel J. Advances in hematopoietic stem cell transplantation in childhood and adolescent lymphomas. Biol Blood Marrow Transplant. 2013;19:38–43.
Gopal AK, Guthrie KA, Rajendran J, Pagel JM, Oliveira G, Maloney DG, et al. 90Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistant high-risk B-cell lymphoma. Blood. 2011;118:1132–9.
Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS, Mott MR, et al. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood. 2016;127:2980–90.
Lee S, Luo W, Shah T, Yin C, O’Connell T, Chung T, et al. The effects of DLEU1 gene expression in Burkitt lymphoma (BL): potential mechanism of chemoimmunotherapy resistance in BL. Oncotarget. 2017;8:27839–53.
Grigg AP, Seymour JF. Graft versus Burkitt’s lymphoma effect after allogeneic marrow transplantation. Leuk Lymphoma. 2002;43:889–92.
El-Mallawany NK, Cairo MS. Advances in the diagnosis and treatment of childhood and adolescent B-cell non-Hodgkin lymphoma. Clin Adv Hematol Oncol. 2015;13:113–23.
Satwani P, Jin Z, Martin PL, Bhatia M, Garvin JH, George D, et al. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma. Leukemia. 2015;29:448–55.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Fujita, N., Kobayashi, R., Atsuta, Y. et al. Hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory B-cell non-Hodgkin lymphoma. Int J Hematol 109, 483–490 (2019). https://doi.org/10.1007/s12185-019-02608-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-019-02608-y