Shifting Paradigms: The Case of Autologous Reconstitution After an Upfront Matched Unrelated Hematopoietic Cell Transplantation for Severe Acquired Aplastic Anemia in a Child

Overview

Journal Medicina (Kaunas)

Publisher MDPI

Specialty General Medicine

Date 2023 Nov 25

PMID 38003941

Authors

Cecile Pochon

Marion Lubnau

Simona Pagliuca

Affiliations

Soon will be listed here.

Abstract

During the last few years, the therapeutic landscape of idiopathic aplastic anemia (IAA) has been profoundly revolutionized by the increased use of alternative transplant procedures, such that today hematopoietic cell transplantation (HCT) from a matched unrelated donor (MUD) has been suggested as a possible first line strategy in pediatric patients with severe IAA, in the absence of a matched related donor. However, in this particular context, outcomes and early and long-term toxicities remain to be determined, as compared to non-transplant procedures. While prospective trials are ongoing, we report here the case of a 12-year-old boy with IAA, receiving an upfront bone marrow HCT from a MUD, who experienced early graft rejection associated with autologous hematological recovery, which could induce remission of his hemopathy. This case offers the opportunity to discuss the challenges associated with these new transplant paradigms and provides a brief review of the literature regarding the issue of autologous recoveries after allogeneic HCT in IAA.

References

Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel S, Cook R, Griffin M . Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med. 2022; 386(1):11-23. DOI: 10.1056/NEJMoa2109965. View

Speck B, Cornu P, Jeannet M, Nissen C, BURRI H, Groff P . Autologous marrow recovery following allogeneic marrow transplantation in a patient with severe aplastic anemia. Exp Hematol. 1976; 4(3):131-7. View

Marsh J, Gupta V, Lim Z, Ho A, Ireland R, Hayden J . Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia. Blood. 2011; 118(8):2351-7. DOI: 10.1182/blood-2010-12-327536. View

Lee J, Sicre de Fontbrune F, Lee L, Pessoa V, Gualandro S, Fureder W . Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2018; 133(6):530-539. PMC: 6367644. DOI: 10.1182/blood-2018-09-876136. View

Tichelli A, Peffault de Latour R, Passweg J, Knol-Bout C, Socie G, Marsh J . Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a Severe Aplastic Anemia Working.... Haematologica. 2019; 105(5):1223-1231. PMC: 7193468. DOI: 10.3324/haematol.2019.222562. View

Liu H, Sun Z, Geng L, Wang X, Ding K, Tang B . Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival. Bone Marrow Transplant. 2012; 47(9):1186-90. DOI: 10.1038/bmt.2011.251. View

Pulsipher M, Lehmann L, Bertuch A, Sasa G, Olson T, Nakano T . A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of.... Pediatr Blood Cancer. 2020; 67(10):e28444. PMC: 9533334. DOI: 10.1002/pbc.28444. View

Devillier R, Dalle J, Kulasekararaj A, dAveni M, Clement L, Chybicka A . Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party. Haematologica. 2016; 101(7):884-90. PMC: 5004469. DOI: 10.3324/haematol.2015.138727. View

Alotaibi H, Aljurf M, de Latour R, Alfayez M, Bacigalupo A, El Fakih R . Upfront Alternative Donor Transplant versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack a Fully HLA-Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies, on Behalf of the Severe Aplastic.... Transplant Cell Ther. 2021; 28(2):105.e1-105.e7. DOI: 10.1016/j.jtct.2021.10.006. View

10.

Bacigalupo A, Locatelli F, Lanino E, Marsh J, Socie G, Maury S . Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant. 2005; 36(11):947-50. DOI: 10.1038/sj.bmt.1705165. View

11.

Kulasekararaj A, Hill A, Rottinghaus S, Langemeijer S, Wells R, Gonzalez-Fernandez F . Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2018; 133(6):540-549. PMC: 6368201. DOI: 10.1182/blood-2018-09-876805. View

12.

Bacigalupo A . Alternative donor transplants for severe aplastic anemia. Hematology Am Soc Hematol Educ Program. 2018; 2018(1):467-473. PMC: 6245994. DOI: 10.1182/asheducation-2018.1.467. View

13.

Li Y, Sheng Z, Niu S, Ge L, Ren C, Zou Y . Rapid and complete reconstitution of autologous haemopoiesis after cord blood infusion in treatment-naive patients with severe aplastic anemia receiving high-dose cyclophosphamide/ATG therapy. Eur J Haematol. 2012; 90(1):45-50. DOI: 10.1111/ejh.12033. View

14.

Piccin A, McCann S, Socie G, Oneto R, Bacigalupo A, Locasciulli A . Survival of patients with documented autologous recovery after SCT for severe aplastic anemia: a study by the WPSAA of the EBMT. Bone Marrow Transplant. 2009; 45(6):1008-13. DOI: 10.1038/bmt.2009.296. View

15.

Jaing T, Huang I, Chen S, Yang C, Liang D, Hung I . Cord blood transplantation in children with relapsed or refractory severe aplastic anemia. J Pediatr Hematol Oncol. 2010; 33(1):18-21. DOI: 10.1097/MPH.0b013e3181f46e51. View

16.

Samarasinghe S, Steward C, Hiwarkar P, Saif M, Hough R, Webb D . Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience. Br J Haematol. 2012; 157(3):339-46. DOI: 10.1111/j.1365-2141.2012.09066.x. View

17.

Devillier R, Eikema D, Dufour C, Aljurf M, Wu D, Maschan A . Graft--host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT. Haematologica. 2023; 108(9):2305-2315. PMC: 10483355. DOI: 10.3324/haematol.2022.281876. View

18.

Salamonowicz-Bodzioch M, Rosa M, Fraczkiewicz J, Gorczynska E, Gul K, Janeczko-Czarnecka M . Fludarabine-Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia. J Clin Med. 2021; 10(19). PMC: 8509585. DOI: 10.3390/jcm10194416. View

19.

Iftikhar R, Chaudhry Q, Anwer F, Neupane K, Rafae A, Mahmood S . Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies. Blood Rev. 2020; 47:100772. DOI: 10.1016/j.blre.2020.100772. View

20.

DeZern A, Zahurak M, Symons H, Cooke K, Rosner G, Gladstone D . Haploidentical BMT for severe aplastic anemia with intensive GVHD prophylaxis including posttransplant cyclophosphamide. Blood Adv. 2020; 4(8):1770-1779. PMC: 7189283. DOI: 10.1182/bloodadvances.2020001729. View