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Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies.
Biol Blood Marrow Transplant. 2017 Feb; 23(2):325-332.BB

Abstract

Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT.

Authors+Show Affiliations

Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: oklein2@jhmi.edu.Johns Hopkins University School of Medicine, Baltimore, Maryland.Johns Hopkins University School of Medicine, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.Pediatric Blood and Marrow Transplantation Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland.

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

27888014

Citation

Klein, Orly R., et al. "Nonmyeloablative Haploidentical Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients With High-Risk Hematologic Malignancies." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 23, no. 2, 2017, pp. 325-332.
Klein OR, Buddenbaum J, Tucker N, et al. Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biol Blood Marrow Transplant. 2017;23(2):325-332.
Klein, O. R., Buddenbaum, J., Tucker, N., Chen, A. R., Gamper, C. J., Loeb, D., Zambidis, E., Llosa, N. J., Huo, J. S., Robey, N., Holuba, M. J., Kasamon, Y. L., McCurdy, S. R., Ambinder, R., Bolaños-Meade, J., Luznik, L., Fuchs, E. J., Jones, R. J., Cooke, K. R., & Symons, H. J. (2017). Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 23(2), 325-332. https://doi.org/10.1016/j.bbmt.2016.11.016
Klein OR, et al. Nonmyeloablative Haploidentical Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients With High-Risk Hematologic Malignancies. Biol Blood Marrow Transplant. 2017;23(2):325-332. PubMed PMID: 27888014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. AU - Klein,Orly R, AU - Buddenbaum,Jessica, AU - Tucker,Noah, AU - Chen,Allen R, AU - Gamper,Christopher J, AU - Loeb,David, AU - Zambidis,Elias, AU - Llosa,Nicolas J, AU - Huo,Jeffrey S, AU - Robey,Nancy, AU - Holuba,Mary Jo, AU - Kasamon,Yvette L, AU - McCurdy,Shannon R, AU - Ambinder,Richard, AU - Bolaños-Meade,Javier, AU - Luznik,Leo, AU - Fuchs,Ephraim J, AU - Jones,Richard J, AU - Cooke,Kenneth R, AU - Symons,Heather J, Y1 - 2016/11/22/ PY - 2016/09/02/received PY - 2016/11/21/accepted PY - 2016/11/27/pubmed PY - 2018/2/28/medline PY - 2016/11/27/entrez KW - Acute leukemia KW - Cyclophosphamide KW - HLA-haploidentical transplantation KW - Lymphoma KW - Myelodysplastic syndrome KW - Nonmyeloablative bone marrow transplantation SP - 325 EP - 332 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 23 IS - 2 N2 - Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious for adult patients with hematologic malignancies. We report data for pediatric/young adult patients with high-risk hematologic malignancies (n = 40) treated with nonmyeloablative haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, and total body irradiation. Post-transplantation immunosuppression consisted of cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment occurred in 29 of 32 (91%), with median time to engraftment of neutrophils >500/µL of 16 days (range, 13 to 22) and for platelets >20,000/µL without transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were 33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with 7% moderate-to-severe chronic GVHD, according to National Institutes of Health consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%. The cumulative incidence of relapse at 2 years was 52%. With a median follow-up of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival were 56% and 43%, respectively. Thus, we demonstrate excellent rates of engraftment, GVHD, and TRM in pediatric/young adult patients treated with this regimen. This approach is a widely available, safe, and feasible option for pediatric and young adult patients with high-risk hematologic malignancies, including those with a prior history of myeloablative BMT and/or those with comorbidities or organ dysfunction that preclude eligibility for myeloablative BMT. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/27888014/Nonmyeloablative_Haploidentical_Bone_Marrow_Transplantation_with_Post_Transplantation_Cyclophosphamide_for_Pediatric_and_Young_Adult_Patients_with_High_Risk_Hematologic_Malignancies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(16)30516-X DB - PRIME DP - Unbound Medicine ER -