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European journal of haematology
Jun, 2023;110 (6): 659-668.

Prognosis of patients with acute lymphoblastic leukaemia relapsing after allogeneic stem cell transplantation.

Christelle Ferra Coll, Mireia Morgades de la Fe, Laura Prieto García, Carlos Pinho Vaz, María Inmaculada Heras Fernando, Rebeca Bailen Almorox, Irene Garcia-Cadenas, Marisa Calabuig Muñoz, Teresa Zudaire Ripa, Joud Zanabili Al-Sibai, Sandra Novoa, Beatriz Aguado, Anna Torrent Catarineu, Oriana López-Godino, Rodrigo Martino Bofarull, Mi Kwon, Antonio Campos Júnior, Dolores Caballero Barrigón, Josep-Maria Ribera Santasusana
Author Information
  1. Christelle Ferra Coll: Clinical Hematology Department, Institut Català d'Oncologia, Institut de Recerca contra la Leucemia Josep Carreras, Hospital Germans Trias i Pujol. Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain. ORCID
  2. Mireia Morgades de la Fe: Clinical Hematology Department, Institut Català d'Oncologia, Institut de Recerca contra la Leucemia Josep Carreras, Hospital Germans Trias i Pujol. Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain. ORCID
  3. Laura Prieto García: Hematology Department, Hospital Universitario de Salamanca, IBSAL (Instituto Biosanitario de Salamanca), Salamanca, Spain. ORCID
  4. Carlos Pinho Vaz: Marrow Transplant Department, Instituto Português de Oncologia, Porto, Portugal. ORCID
  5. María Inmaculada Heras Fernando: Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain. ORCID
  6. Rebeca Bailen Almorox: Hematology Department Hospital General Universitario Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. ORCID
  7. Irene Garcia-Cadenas: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. ORCID
  8. Marisa Calabuig Muñoz: Hematology Department, Hospital Universitario Clínico de Valencia, Valencia, Spain. ORCID
  9. Teresa Zudaire Ripa: Hematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. ORCID
  10. Joud Zanabili Al-Sibai: Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain. ORCID
  11. Sandra Novoa: Hematology Department Hospital Universitari Vall d'Hebrón, Universitat Autònoma de Barcelona, Barcelona, Spain. ORCID
  12. Beatriz Aguado: Hematology Department, Hospital Universitario La Princesa, Madrid, Spain. ORCID
  13. Anna Torrent Catarineu: Clinical Hematology Department, Institut Català d'Oncologia, Institut de Recerca contra la Leucemia Josep Carreras, Hospital Germans Trias i Pujol. Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain. ORCID
  14. Oriana López-Godino: Hematology Department, Hospital General Universitario Morales Meseguer, Murcia, Spain. ORCID
  15. Rodrigo Martino Bofarull: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. ORCID
  16. Mi Kwon: Hematology Department Hospital General Universitario Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. ORCID
  17. Antonio Campos Júnior: Marrow Transplant Department, Instituto Português de Oncologia, Porto, Portugal. ORCID
  18. Dolores Caballero Barrigón: Hematology Department, Hospital Universitario de Salamanca, IBSAL (Instituto Biosanitario de Salamanca), Salamanca, Spain. ORCID
  19. Josep-Maria Ribera Santasusana: Clinical Hematology Department, Institut Català d'Oncologia, Institut de Recerca contra la Leucemia Josep Carreras, Hospital Germans Trias i Pujol. Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain. ORCID
PMID: 36813736 DOI: 10.1111/ejh.13947

Abstract

The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo-SCT) are poor, with few data available in this setting.
OBJECTIVE AND METHODS: To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centres in Spain.
RESULTS: Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo-SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis.
CONCLUSION: Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT.

Keywords

acute lymphoblastic leukaemia allogeneic haematopoietic stem cell transplant relapse

References

Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J med. 2015;373:1541-1552. doi:10.1056/NEJMra1400972
Aldoss I, Stein AS. Advances in adult acute lymphoblastic leukemia therapy. Leuk Lymphoma. 2018;59:1033-1050. doi:10.1080/10428194.2017.1354372
Leonard JT, Hayes-Lattin B. Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia; current evidence, and improving outcomes going forward. Curr Hematol Malig Rep. 2018;13:329-340. doi:10.1007/s11899-018-0462-x
Marks DI, Alonso L, Radia R. Allogeneic hematopoietic cell transplantation in adult patients with acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2014;28:995-1009. doi:10.1016/j.hoc.2014.08.008
Poon LM, Hamdi A, Saliba R, et al. Outcomes of adults with acute lymphoblastic leukemia relapsing after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:1059-1064. doi:10.1016/j.bbmt.2013.04.014
Poon LM, Bassett JR, Rondon G, et al. Outcomes of second allogeneic hematopoietic stem cell transplantation for patients with acute lymphoblastic leukemia. Bone Marrow Transplant. 2013;48:666-670. doi:10.1038/bmt.2012.195
Spyridonidis A, Labopin M, Schmid C, et al. Immunotherapy Subcommittee of Acute Leukemia Working Party. Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT. Leukemia. 2012;26:1211-1217. doi:10.1038/leu.2011.351
Aljasem HA, Messner HA, Lipton JH, et al. Outcome following second allogeneic hematopoietic cell transplantation: a single-center experience. Eur J Haematol. 2018;100:308-314. doi:10.1111/ejh.13015
Yaniv I, Krauss AC, Beohou E, et al. Second hematopoietic stem cell transplantation for post-transplantation relapsed acute leukemia in children: a retrospective EBMT-PDWP study. Biol Blood Marrow Transplant. 2018;24:1629-1642. doi:10.1016/j.bbmt.2018.03.002
Al Malki MM, Aldoss I, Stiller T, et al. Outcome of second allogeneic hematopoietic cell transplantation in patients with acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2016;16:519-522. doi:10.1016/j.clml.2016.06.005
Nagler A, Labopin M, Dholaria B, et al. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol. 2019;186:767-776. doi:10.1111/bjh.15973 Epub 2019 May 22.
Topp MS, Gökbuget N, Zugmaier G, et al. Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab cancer. 2021;127:554-559. doi:10.1002/cncr.33298
Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125:2474-2487. doi:10.1002/cncr.32116
Martino M, Alati C, Canale FA, Musuraca G, Martinelli G, Cerchione C. A review of clinical outcomes of car t-cell therapies for b-acute lymphoblastic leukemia. Int J Mol Sci. 2021;22:2150. doi:10.3390/ijms22042150
Shah BD, Ghobadi A, Oluwole OO, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021;398:491-502. doi:10.1016/S0140-6736(21)01222-8
Shah BD, Bishop MR, Oluwole OO, et al. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood. 2021;138:11-22. doi:10.1182/blood.2020009098
Przepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825-828.
Atkinson K. Chronic graft-versus-host disease. Bone Marrow Transplant. 1990;5:69-82.
Filipovich 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;11:945-956. doi:10.1016/j.bbmt.2005.09.004
Bachanova V, Burke MJ, Yohe S, et al. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012;18:963-968. doi:10.1016/j.bbmt.2012.02.012
Hirschbühl K, Labopin M, Houhou M, et al. Mohty M. second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party Bone Marrow Transplant. 2021;56:1190-1199. doi:10.1038/s41409-020-01173-x
Bazarbachi A, Labopin M, Aljurf M, et al. 20-year steady increase in survival of adult patients with relapsed Philadelphia-positive acute lymphoblastic leukemia post allogeneic hematopoietic cell transplantation. Clin Cancer Res. 2022;28:1004-1012. doi:10.1158/1078-0432.CCR-21-2675
Passweg JR, Tiberghien P, Cahn JY, et al. Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia. Bone Marrow Transplant. 1998;21:153-158. doi:10.1038/sj.bmt.1701064
Ferrá C, Sanz J, de la Cámara R, et al. On behalf of GETH (Grupo Español de Trasplante Hematopoyético) and PETHEMA (Programa Español de Tratamiento en Hematología), Spanish Society of Hematology. Unrelated transplantation for poor-prognosis adult acute lymphoblastic leukemia: long-term outcome analysis and study of the impact of hematopoietic graft source. Biol Blood Marrow Transplant. 2010;16:957-966. doi:10.1016/j.bbmt.2010.02.003
Shimoni A. Relapse of acute leukemia after a second allogeneic stem- cell transplantation; is there any hope for cure? Bone Marrow Transplant. 2022 Jan 14;57:336-337. doi:10.1038/s41409-021-01508-2
Ortí G, Sanz J, García-Cadenas I, et al. Analysis of relapse after transplantation in acute leukemia: a comparative on second allogeneic hematopoietic cell transplantation and donor lymphocyte infusions. Exp Hematol. 2018;62:24-32. doi:10.1016/j.exphem.2018.03.002
Arellano ML, Langston A, Winton E, Flowers CR, Waller EK. Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience. Biol Blood Marrow Transplant. 2007;13:116-123. doi:10.1016/j.bbmt.2006.09.005
Eapen M, Giralt SA, Horowitz MM, et al. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant bone marrow transplant. 2004;34:721-727. doi:10.1038/sj.bmt.1704645
Bosi A, Laszlo D, Labopin M, et al. Acute Leukemia Working Party of the European Blood and Marrow Transplant Group. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2001;19:3675-3684. doi:10.1200/JCO.2001.19.16.3675
Andreola G, Labopin M, Beelen D, et al. Long-term outcome and prognostic factors of second allogeneic hematopoietic stem cell transplant for acute leukemia in patients with a median follow-up of 10 years. Bone Marrow Transplant. 2015;50:1508-1512. doi:10.1038/bmt.2015.193
Kharfan-Dabaja MA, Labopin M, Bazarbachi A, et al. Comparing outcomes of a second allogeneic hematopoietic cell transplant using HLA-matched unrelated versus T-cell replete haploidentical donors in relapsed acute lymphoblastic leukemia: a study of the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant. 2021 Sep;56(9):2194-2202. doi:10.1038/s41409-021-01317-7
Zhang M, Huang H. How to combine the two landmark treatment methods-allogeneic hematopoietic stem cell transplantation and chimeric antigen receptor T cell therapy together to cure high-risk B cell acute lymphoblastic leukemia? Front Immunol. 2020;11:611710. doi:10.3389/fimmu.2020.611710

MeSH Term

Humans
Retrospective Studies
Transplantation, Homologous
Neoplasm Recurrence, Local
Hematopoietic Stem Cell Transplantation
Stem Cell Transplantation
Prognosis
Acute Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Journal Article

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