Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Unrelated donor transplantation for relapsed refractory aplastic anemia, with quadruple GvHD prophylaxis

Bone Marrow Transplantation (2025)Cite this article

Subjects

The outcome of unrelated donor (UD) transplants in patients with acquired severe aplastic anemia (SAA) has improved over time [1, 2], such that survival is now comparable to transplants from matched sibling donors (MSD) [3]. Despite high-resolution HLA matching [1], improved supportive care and GvHD prophylaxis, a longer interval from diagnosis to transplant, and older patient age remain negative predictors [4, 5]. The Baltimore group has developed a transplant platform for haploidentical (HAPLO) transplants in SAA, with four drugs for GvHD prophylaxis, namely anti-thymocyte globulin ATG, post-transplant cyclophosphamide (PTCY), a calcineurin inhibitor (CNI), and mycophenolate (MMF) [6]: results have been very good in terms of engraftment and control of GvHD, such that the Baltimore group has moved from HAPLO transplants in relapse/refractory (R/R) patients [6] to upfront transplant at diagnosis of SAA [7]. A small number of patients have been reported in Brazil, using the Baltimore regimen for UD transplants in SAA with encouraging early results [8].

Here we report a multicenter retrospective study of the original Baltimore regimen with TBI 2 Gy and four-drug GvHD prophylaxis, in R/R SAA patients, grafted from UD or MSD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Main transplant outcome.

Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Maury S, Balère-Appert ML, Chir Z, Boiron JM, Galambrun C, Yakouben K, et al. Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica. 2007;92:589–96.

    Article  PubMed  Google Scholar 

  2. Bacigalupo A, Socie' G, Lanino E, Prete A, Locatelli F, Locasciulli A, et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low-dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA Working Party. Haematologica. 2010;95:976–982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bacigalupo A, Socié G, Hamladji RM, Aljurf M, Maschan A, Kyrcz-Krzemien S, et al. On behalf of the Aplastic Anemia Working Party of the European Group for Blood Marrow Transplantation. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica. 2015;100:696–702.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Devillier R, Eikema DJ, Dufour C, Aljurf M, Wu D, Maschan A, et al. Graft-versus-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;108:2305–15.

    PubMed  PubMed Central  Google Scholar 

  5. Giammarco S, Peffault de Latour R, Sica S, Dufour C, Socie G, Passweg J, et al. European Group for Blood and Marrow Transplantation Severe Aplastic Anemia Working Party. Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved? Blood. 2018;131:1989–92.

  6. DeZern AE, Zahurak M, Symons H, Cooke K, Jones RJ, Brodsky RA. Alternative Donor transplantation with high-dose post-transplantation Cyclophosphamide for refractory severe aplastic anemia. Biol Blood Marrow Transpl. 2017;23:498–504.

    Article  CAS  Google Scholar 

  7. DeZern AE, Zahurak M, Symons HJ, Cooke KR, Huff CA, Jain T, et al. Alternative donor BMT with posttransplant cyclophosphamide as initial therapy for acquired severe aplastic anemia. Blood. 2023;141:3031–8.

    CAS  PubMed  Google Scholar 

  8. Arcuri LJ, Nabhan SK, Loth G, Atta EH, Oliveira M, Nichele S, et al. A case series of post-transplantation cyclophosphamide in unrelated donor hematopoietic cell transplantation for aplastic anemia. Biol Blood Marrow Transpl. 2020;26:e222–e226.

    Article  CAS  Google Scholar 

  9. Montoro J, Eikema DJ, Tuffnell J, Potter V, Kalwak K, Halkes CJM, et al. Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT. Blood. 2024;144:323–33.

    Article  CAS  PubMed  Google Scholar 

  10. Risitano A, Eikema DJ, Tuffnell BP, Potter V, Sicre de Fontbrune F, Benakli M, et al. Role of age and donor type in 3646 severe aplastic anemia patients undergoing hemopoietic stem cell transplantation in 2011-2020: a retrospective EBMT SAAWP study. Blood. 2024;144:595.S1.

    Article  Google Scholar 

  11. Fujimoto A, Hiramoto N, Yamasaki S, Inamoto Y, Uchida N, Maeda T, et al. Risk factors and predictive scoring system for post-transplant lymphoproliferative disorder after hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2019;25:1441–9.

    Article  Google Scholar 

  12. Peffault de Latour R, Chevret S, Juber C, Sirvent A, Galambrun C, Ruggeri A, et al. Unrelated cord blood transplantation in patients with idiopathic refractory aplastic anemia : a nationwide phase 2 study. Blood. 2018;132:750–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by AIRC Milano, grant to AB 2017. This study was supported by FARITMO, Genova, Italy.

Author information

Authors and Affiliations

  1. Dipartimento di Scienze di Laboratorio ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

    Sabrina Giammarco, Andrea Bacigalupo, Patrizia Chiusolo, Elisabetta Metafuni, Federica Sora, Maria Assunta Limongiello & Simona Sica

  2. Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Università Cattolica del Sacro Cuore, Roma, Italy

    Andrea Bacigalupo, Patrizia Chiusolo, Federica Sora & Simona Sica

  3. Divisione di Ematologia, Ospedale di Alessandria, Alessandria, Italy

    Nicola Mordini

  4. SC Ematologia, AO S Croce e Carlo, Cuneo, Italy

    Francesco Zallio

  5. Divisione di Ematologia, Ospedale di Bolzano, Bolzano, Italy

    Irene Cavattoni

  6. BMT Unit, AOR Villa Sofia Cervello, Palermo, Italy

    Luca Castagna

  7. Ematologia, Policlinico Umberto I, Roma, Italy

    Walter Barberi

  8. SS Trapianto Cellule Staminali AOU Citta’ della Salute e della Scienza, Torino, Italy

    Alessandro Busca

  9. Cattedra di Ematologia, Universita’ di Udine, Udine, Italy

    Francesca Patriarca

  10. SC Ematologia con Trapianto di Midollo Osseo, Azienda Ospedaliera, Perugia, Italy

    Alessandra Carotti

  11. Centro Trapianti di Midollo Osseo; Fondazione IRCCS Ca’Granda, Ospedale Maggiore, Policlinico Milano, Milano, Italy

    Giorgia Saporiti

  12. UOC Ematologia con Trapianto, Azienda.Ospedaliera Universitaria Policlinico Bari, Bari, Italy

    Paola Carluccio

  13. Ematologia, Ospedale Careggi, Firenze, Italy

    Chiara Nozzoli

  14. Ematologia ed Trapianto di Cellule Staminali – Ospedale Ca’Foncello, Treviso, Italy

    Marta Stanzani

  15. U.O.C Ematologia e Centro Trapianti CSE Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Angelo Michele Carella

Authors
  1. Sabrina Giammarco
    View author publications

    Search author on:PubMed Google Scholar

  2. Andrea Bacigalupo
    View author publications

    Search author on:PubMed Google Scholar

  3. Nicola Mordini
    View author publications

    Search author on:PubMed Google Scholar

  4. Francesco Zallio
    View author publications

    Search author on:PubMed Google Scholar

  5. Irene Cavattoni
    View author publications

    Search author on:PubMed Google Scholar

  6. Luca Castagna
    View author publications

    Search author on:PubMed Google Scholar

  7. Walter Barberi
    View author publications

    Search author on:PubMed Google Scholar

  8. Patrizia Chiusolo
    View author publications

    Search author on:PubMed Google Scholar

  9. Elisabetta Metafuni
    View author publications

    Search author on:PubMed Google Scholar

  10. Federica Sora
    View author publications

    Search author on:PubMed Google Scholar

  11. Maria Assunta Limongiello
    View author publications

    Search author on:PubMed Google Scholar

  12. Alessandro Busca
    View author publications

    Search author on:PubMed Google Scholar

  13. Francesca Patriarca
    View author publications

    Search author on:PubMed Google Scholar

  14. Alessandra Carotti
    View author publications

    Search author on:PubMed Google Scholar

  15. Giorgia Saporiti
    View author publications

    Search author on:PubMed Google Scholar

  16. Paola Carluccio
    View author publications

    Search author on:PubMed Google Scholar

  17. Chiara Nozzoli
    View author publications

    Search author on:PubMed Google Scholar

  18. Marta Stanzani
    View author publications

    Search author on:PubMed Google Scholar

  19. Angelo Michele Carella
    View author publications

    Search author on:PubMed Google Scholar

  20. Simona Sica
    View author publications

    Search author on:PubMed Google Scholar

Contributions

SG and APB designed the study; SG and AB merged, revised and analyzed the data from all participating centers; PC, FS, EM and MAL were involved in the management of patients at Fondazione Policlinico Universitario A. Gemelli IRCCS; NM was involved in the management of patients at Alessandria Hospital; FZ was involved in the management of patients at S Croce e Carlo Hospital in Cuneo, IR was involved in the management of patients at Bolzano Hospital; LC was involved in the management of patients in the BMT Unit, at Villa Sofia Cervello Hospital in Palermo; WB was involved in the management of patients in Hematology Departement at, Policlinico Umberto I Hospital in Rome; AB was involved in the management of patients in Citta’ della Salute e della Scienza Hospital in Turin; FP was involved in the management of patient at Udine Hospital; AC was involved in the management of patient at Perugia Hospital; GS was involved in the management of patients at IRCCS Ca’Granda, Hospital Maggiore in Milan; PC was involved in the management of patients at Bari Hsopital; CN was involved in the management of patients at Careggi Hsopriola in Florence; MS was involved in the management of patients at Treviso Hospital; AMC was involved in the management of patients at IRCCS Casa Sollievo della Sofferenza in San Giovanni Rotondo; SG and APB wrote the paper; SS revised the manuscript.

Corresponding author

Correspondence to Andrea Bacigalupo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giammarco, S., Bacigalupo, A., Mordini, N. et al. Unrelated donor transplantation for relapsed refractory aplastic anemia, with quadruple GvHD prophylaxis. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02750-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41409-025-02750-8

Search

Advanced search

Quick links