Total body irradiation-free haploidentical peripheral blood stem cell transplantation compared to related and unrelated donor transplantation in pediatrics with acute lymphoblastic leukemia.
Humans
Child
Adolescent
Peripheral Blood Stem Cell Transplantation
/ adverse effects
Unrelated Donors
Transplantation, Homologous
/ adverse effects
Cyclophosphamide
/ therapeutic use
Hematopoietic Stem Cell Transplantation
/ adverse effects
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Graft vs Host Disease
/ etiology
Recurrence
Transplantation Conditioning
/ methods
Cyclosporins
Retrospective Studies
acute lymphoblastic leukemia
haploidentical
hematopoietic stem cell transplantation
pediatrics
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
10
01
2023
received:
23
11
2022
accepted:
26
01
2023
pubmed:
24
2
2023
medline:
25
3
2023
entrez:
23
2
2023
Statut:
ppublish
Résumé
Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant. The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide. The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01). Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients.
Sections du résumé
BACKGROUND
Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant.
PATIENTS AND METHODS
The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide.
RESULTS
The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01).
CONCLUSION
Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients.
Substances chimiques
Cyclophosphamide
8N3DW7272P
Cyclosporins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e30255Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Wu C, Li W. Genomics and pharmacogenomics of pediatric acute lymphoblastic leukemia. Crit Rev Oncol Hematol. 2018;126:100-111.
Pui C-H, Mullighan CG, Evans WE, et al. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? 2012;120(6):1165-1174.
Nguyen K, Devidas M, Cheng S-C, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-2150.
Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541-1552.
Vrooman LM, Silverman LB. Treatment of childhood acute lymphoblastic leukemia: prognostic factors and clinical advances. Curr Hematol Malig Rep. 2016;11(5):385-394.
Schrappe M, Hunger SP, Pui C-H, et al. Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med. 2012;366(15):1371-1381.
Pulsipher MA, Peters C, Pui C-H. High-risk pediatric acute lymphoblastic leukemia: to transplant or not to transplant? Biol Blood Marrow Transplant. 2011;17(1):S137-S148.
Ottinger HD, Ferencik S, Beelen DW, et al. Hematopoietic stem cell transplantation: contrasting the outcome of transplantations from HLA-identical siblings, partially HLA-mismatched related donors, and HLA-matched unrelated donors. Blood. 2003;102(3):1131-1137.
Gragert L, Eapen M, Williams E, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the US registry. N Engl J Med. 2014;371(4):339-348.
Johansen K, Schneider JF, Mccaffree MA, et al. Efforts of the United States’ National Marrow Donor Program and Registry to improve utilization and representation of minority donors. Transfus Med. 2008;18(4):250-259.
Aljurf M, Weisdorf D, Hashmi SK, et al. Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic stem cell transplantation program in countries with limited resources (part II): clinical, technical and socio-economic considerations. Hematol Oncol Stem Cell Ther. 2020;13(1):7-16.
Ruggeri A, Sun Y, Labopin M, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102(2):401-410.
Ciurea SO, Zhang M-J, Bacigalupo AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126(8):1033-1040.
Fabricius WA, Ramanathan M. Review on haploidentical hematopoietic cell transplantation in patients with hematologic malignancies. Adv Hematol. 2016;2016:5726132.
Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Am Soc Hematol Educ Program. 2012;2012(1):230-236.
Kongtim P, Lee DA, Cooper LJN, et al. Haploidentical hematopoietic stem cell transplantation as a platform for post-transplantation cellular therapy. Biol Blood Marrow Transplant. 2015;21(10):1714-1720.
Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15(5):1767-1777.
Mo XD, Tang B-L, Zhang X-H, et al. Comparison of outcomes after umbilical cord blood and unmanipulated haploidentical hematopoietic stem cell transplantation in children with high-risk acute lymphoblastic leukemia. Int J Cancer. 2016;139(9):2106-2115.
Fuchs EJ, O'donnell PV, Eapen M, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420-428.
Gaballa S, Ge I, El Fakih R, et al. Results of a 2-arm, phase 2 clinical trial using post-transplantation cyclophosphamide for the prevention of graft-versus-host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation. Cancer. 2016;122(21):3316-3326.
Wieduwilt MJ, Metheny L, Zhang M-J, et al. Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia. Blood Adv. 2021;6(1):339-357.
Al Malki MM, Yang D, Labopin M, et al. Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation. Blood Adv. 2020;4(9):2073-2083.
Berger M, Lanino E, Cesaro S, et al. Feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide for children and adolescents with hematologic malignancies: an AIEOP-GITMO retrospective multicenter study. Biol Blood Marrow Transplant. 2016;22(5):902-909.
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.
Ruggeri A, Galimard J-E, Paina O, et al. Outcomes of unmanipulated haploidentical transplantation using post-transplant cyclophosphamide (PT-Cy) in pediatric patients with acute lymphoblastic leukemia. Transplant Cell Ther. 2021;27(5):424.e1-424.e9.
Bresters D, Lawitschka A, Cugno C, et al. Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters. Bone Marrow Transplant. 2016;51(11):1482-1489.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825-828.
Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28(3):250-259.
Tanaka Y, Kurosawa S, Tajima K, et al. Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016;51(4):553-559.
Pierro J, Hogan LE, Bhatla T, et al. New targeted therapies for relapsed pediatric acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2017;17(8):725-736.
Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood J Am Soc Hematol. 2011;118(23):6006-6017.
Sanz J, Galimard J-E, Labopin M, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol. 2020;13(1):46.
Zheng F-M, Zhang Xi, L C-Fu, et al. Haploidentical-versus identical-sibling transplant for high-risk pediatric AML: a multi-center study. Cancer Commun. 2020;40(2-3):93-104.
Friend BD, Bailey-Olson M, Melton A, et al. The impact of total body irradiation-based regimens on outcomes in children and young adults with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2020;67(2):e28079.
Peters C, Dalle J-H, Locatelli F, et al. Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority phase III study. J Clin Oncol. 2021;39(4):295-307.
Davies SM, Ramsay NKC, Klein JP, et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000;18(2):340-347.
Socié G, Curtis RE, Deeg HJ, et al. New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. J Clin Oncol. 2000;18(2):348-348.
Baker KS, Bresters D, Sande JE. The burden of cure: long-term side effects following hematopoietic stem cell transplantation (HSCT) in children. Pediatr Clin. 2010;57(1):323-342.
Bresters D, Emons JAM, Nuri N, et al. Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood. Pediatr Blood Cancer. 2014;61(11):2048-2053.
Overbeek A, Van Den Berg MH, Kremer LCm, et al. A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges. BMC Cancer. 2012;12:363.
Dalle J, Lucchini G, Balduzzi A, et al. State-of-the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation: a report on the expert meeting of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) in Baden, Austria, 29-30 September 2015. Bone Marrow Transplant. 2017;52(7):1029-1035.
Hamidieh AA, Monzavi SM, Kaboutari M, et al. Outcome analysis of pediatric patients with acute lymphoblastic leukemia treated with total body irradiation-free allogeneic hematopoietic stem cell transplantation: comparison of patients with and without central nervous system involvement. Biol Blood Marrow Transplant. 2017;23(12):2110-2117.
Esfandbod M, Enshaei M, Monzavi SM, et al. Radiation-Free myeloablative allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia: a comparison of outcomes between patients with and without central nervous system involvement. Leuk Res. 2021;111:106703.
Willasch AM, Peters C, Sedláček P, et al. Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy-a multicenter EBMT-PDWP study. Bone Marrow Transplant. 2020;55(8):1540-1551.
Handgretinger R, Lang P. Could (should) we abandon total body irradiation for conditioning in children with leukemia. Blood Rev. 2022;6:100966.
Xue YJ, Cheng Yi-F, Lu Ai-D, et al. Allogeneic hematopoietic stem cell transplantation, especially haploidentical, may improve long-term survival for high-risk pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era. Biol Blood Marrow Transplant. 2019;25(8):1611-1620.
Wang Y, Liu D-H, Xu L-P, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant. 2011;17(6):821-830.
Chang Y-J, Wang Yu, Liu Y-R, et al. Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol. 2017;10(1):134.
Salvatore 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.
Yu S, Huang F, Wang Yu, et al. Haploidentical transplantation might have superior graft-versus-leukemia effect than HLA-matched sibling transplantation for high-risk acute myeloid leukemia in first complete remission: a prospective multicentre cohort study. Leukemia. 2020;34(5):1433-1443.
Erbey F, Akçay A, Atay D, et al. Comparison of outcomes after HLA-matched unrelated and αβ T-cell-depleted haploidentical hematopoietic stem cell transplantation for children with high-risk acute leukemia. Pediatr Transplant. 2018;22(4):e13192.
Simonin M, Dalissier A, Labopin M, et al. More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia: a retrospective study on behalf of the EBMT Paediatric Diseases Working Party. Bone Marrow Transplant. 2017;52(7):1071-1073.
Kato M, Kurata M, Kanda J, et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transplant. 2019;54(1):68-75.
Bashey A, Zhang Xu, Sizemore CA, 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):1310-1316.
Xiao-Jun H, Lan-Ping Xu, Kai-Yan L, et al. Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res. 2009;15(14):4777-4783.
Klingebiel T, Cornish J, Labopin M, et al. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the acute leukemia and pediatric disease working parties of the European Blood and Marrow Transplant Group. Blood J Am Soc Hematol. 2010;115(17):3437-3446.
Lin CH, Su Y-J, Hsu C-Y, et al. Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia. Transpl Infect Dis. 2019;21(4):e13096.