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Successful allogeneic CD34+ hematopoietic stem cell boost for prolonged cytopenias following CAR T-cell therapy in B-cell acute lymphoblastic leukemia. On behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC)

Bone Marrow Transplantation volume 60, pages 250–253 (2025)Cite this article

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Chimeric antigen receptor (CAR) T-cell therapy has a remarkable impact on the outcome of pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) [1, 2]. Hematological toxicity leading to peripheral-blood cytopenias is one of the most common and severe long-term adverse effects [3]. Moreover, severe cytopenias result in life-threatening bleeding and infectious events, being a major driver of the morbidity and mortality observed after CAR T-cell therapy [4].

Hemato-toxicity after CAR T cell administration can be multifactorial and closely associated with CAR-T and disease-associated inflammation in addition to baseline bone marrow (BM) reserve. However, the underlying pathophysiology of prolonged cytopenias after CAR T-cell infusion remains poorly understood and represents a clinical challenge with a paucity of data to guide management [5, 6]. In this setting, several off-label approaches have been described, including transfusion support, use of granulocyte colony stimulating factors, thrombopoietin analogues and erythroid stimulators. Hematopoietic stem cell (HSC) boost has also been used to treat poor graft function after CAR-T cell therapy mainly based on cryopreserved autologous infusion [7, 8]. However, the experience using allogeneic CD34+ HSC boost remains anecdotal.

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Data availability

The datasets generated and analyzed during the current study are not publicly available due to the lack of formal authorization for this porpoise by the patients providing their clinical information for this study but they are available from the corresponding author and GETH-TC on reasonable request.

References

  1. Rives S, Maude SL, Hiramatsu H, Baruchel A, Bader P, Bittencourt H, et al. Tisagenlecelucel in pediatric and young adult patients (PTS) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL): final analyses from the ELIANA study. HemaSphere. 2022;6:p13–14. https://doi.org/10.1097/01.HS9.0000843344.19780.98

    Article  Google Scholar 

  2. Ortíz-Maldonado V, Rives S, Castellà M, Alonso-Saladrigues A, Benítez-Ribas D, Caballero-Baños M, et al. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19(+) Relapsed/Refractory Malignancies. J Mol Ther. 2021;29:636–44. https://doi.org/10.1016/j.ymthe.2020.09.027.

    Article  CAS  Google Scholar 

  3. Jain T, Knezevic A, Pennisi M, Chen Y, Ruiz JD, Purdon TJ, et al. Hematopoietic recovery in patient receiving chimeric antigen receptor T-cell therapy for hematologic malignancies. Blood Adv. 2020;4:3776–87. https://doi.org/10.1182/bloodadvances.2020002509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cordas-Dos Santos DM, Tix T, Shouval T, Gafter-Gvili A, Alberge JB, Scheffer ER, et al. A systematic review and meta-analysis of non-relapse mortality after CAR T cell therapy. Nat Med. 2024;30:2667–78. https://doi.org/10.1038/s41591-024-03084-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fried S, Avigdor A, Bielorai B, Meir A, Besser MJ, Schachter J, et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transpl. 2019;54:1643–50.

    Article  CAS  Google Scholar 

  6. Rejeski K, Subklewe M, Aljurf M, Bachy E, Balduzzi A, Barba P, et al. Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood. 2023;142:865–77. https://doi.org/10.1182/blood.2023020578

    Article  CAS  PubMed  Google Scholar 

  7. Jain T, Olson TS, Locke FL. How I treat cytopenias after CAR T-cell therapy. Blood. 2023;141:2460–9. https://doi.org/10.1182/blood.2022017415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gagelmann N, Wulf GG, Duell J, Glass B, van Heteren P, von Tresckow B, et al. Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy: a GLA/DRST study. Blood Adv. 2023;7:555–9. https://doi.org/10.1182/bloodadvances.2022008042.

    Article  CAS  PubMed  Google Scholar 

  9. Rejeski K, Greco R, Onida F, Sánchez-Ortega I, Bonini C, Sureda A, et al. An international survey on grading, diagnosis, and management of immune effector cell-associated hemato-toxicity (ICAHT) following CAR T-cell therapy on behalf of the EBMT and EHA. Hemasphere. 2023;7:e889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, et al. CAR-HEMATOTOX: a model for CAR T-cel l related hematologic toxicity in relapsed/ refractory large B-cell lymphoma. Blood. 2021;138:2499–513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rejeski K, Burchert A, Iacoboni G, Sesques P, Francesky L, Bücklein V, et al. Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy. Blood Adv. 2022;6:4719–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mullanfiroze K, Lazareva A, Chu J, Williams L, Burridge S, Silva J, et al. CD34+-selected stem cell boost can safely improve cytopenias following CAR T-cell therapy. Blood Adv. 2022;6:4715–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lipsitt A, Beattie L, Harstead E, Li Y, Goorha S, Maron G, et al. Allogeneic CD34+selected hema-topoietic stem cell boost following CAR T-cell therapy in a patient withprolonged cytopenia and active infection. Pediatr Blood Cancer. 2023;70:e30166.

    Article  CAS  PubMed  Google Scholar 

  14. Shahzad M, Siddiqui RS, Anwar I, Chaudhary SG, Ali T, Naseem N, et al. Outcomes with CD34-selected stem cell boost for poor graft function after allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transpl Cell Ther. 2021;27:877.e1–877.e8.

    Article  CAS  Google Scholar 

  15. Klyuchnikov E, El-Cheikh J, Sputtek A, Lioznov M, Calmels B, Furst S, et al. CD34.-Selected Stem Cell Boost without Further Conditioning for Poor Graft Function after Allogeneic Stem Cell Transplantation in patients with Hematological Malignancies. Biol Blood Marrow Transpl. 2014;20:382e386.

    Article  Google Scholar 

  16. Bader P, Alonso A, Attarbaschi A, Bodmer N, Boing H, Burridge S, et al. Treatment of post-transplant relapse in children, adolescents and young adults with BCP ALL using CD19-CAR-T: A European retrospective analysis of real-world data. Hemasphere. 2023;7:e239539.

    Article  Google Scholar 

  17. Penack O, Pecznski C, Koenecke C, Polge E, Kuhnl A, Fegueux N, et al. Severe cytopenia after CD19 CAR T-cell therapy: a retrospective study from the EBMT Transplant Complications Working Party. J Immunother Cancer. 2023;11:e006406. https://doi.org/10.1136/jitc-2022-006406.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, et al. GLA/DRST real-world outcome analysis of car T-cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140:349–58.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the clinical care teams for their assistance in providing excellent patient care.

Author information

Authors and Affiliations

  1. Pediatric Unit, Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS) / CSIC, Universidad de Sevilla, Seville, Spain

    Águeda Molinos-Quintana, Concepción Pérez de Soto & José María Pérez-Hurtado

  2. Haematology Department, Hospital Clinic de Barcelona, Barcelona, Spain

    Nuria Martínez-Cibrian & Valentín Ortiz-Maldonado

  3. CAR T-cell Unit, Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu de Barcelona, Barcelona, Spain

    Anna Alonso-Saladrigues

  4. Institut de Recerca Sant Joan de Déu, Barcelona, Spain

    Anna Alonso-Saladrigues

  5. Medicine and Surgery School, University of Barcelona, Barcelona, Spain

    Anna Alonso-Saladrigues

  6. Pediatric Hemato-Oncology Department, University Hospital La Paz, Institute for Health Research (IdiPAZ), Universidad Autónoma de Madrid, Madrid, Spain

    Víctor Galán-Gómez & Berta González-Martínez

  7. Haematology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    Rebeca Bailén

  8. Pediatric Hemato-Oncology Department, Peditric University Hospital del Niño Jesús, Madrid, Spain

    Susana Buendía-López

  9. Pediatry Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Carolina Fuentes-Socorro

  10. Haematology Department, Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón. Universidad Complutense de Madrid, Madrid, Spain

    Mi Kwon

  11. Department of Stem Cell Transplantation, Hospital Infantil Universitario Niño Jesús, Madrid, Spain

    Marta González-Vincent

  12. Pediatric Cancer Center Barcelona (PCCB), Institut de Recerca Sant Joan de Déu, Leukemia and Pediatric Hematology Disorders, Developmental Tumors Biology Group, Barcelona, Spain

    Susana Rives

  13. Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red De Enfermedades Raras (CIBERER), Madrid, Spain

    Susana Rives

  14. Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Universidad de Sevilla, Seville, Spain

    José Antonio Pérez-Simón

Authors
  1. Águeda Molinos-Quintana
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  2. Nuria Martínez-Cibrian
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  4. Víctor Galán-Gómez
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  7. Carolina Fuentes-Socorro
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  8. Mi Kwon
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  9. Marta González-Vincent
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  14. Valentín Ortiz-Maldonado
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  15. José Antonio Pérez-Simón
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Contributions

AM-Q was responsible for designing the study, data curation and formal analyzing data, interpreting results, updating reference list, creating tables and writing original draft. NM-C and AA-S were responsible for designing the study and they contributed to writing the original report and extracting and analyzing data. VG-G, RB, SB-G and CF-S contributed to data extraction and provided feedback on the report. MK, MG-V, CP-S and BG-M contributed to methodology and helped write the manuscript. SR, JMP-H were responsible for conceptualization, methodology and writing and review the manuscript VO-M and JAP-S were responsible for conceptualization and designing the study, screening potencially eligible studies. They supervised the methodology, interpreting results and conclusions. They contributed to writing, review and editing the original draft.

Corresponding authors

Correspondence to Águeda Molinos-Quintana or Valentín Ortiz-Maldonado.

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Competing interests

The authors declare no competing interests.

Ethics

The study involving humans was approved by the local institutional ethics committee: CEI de los Hospitales Universitarios Virgen Macarena y Virgen del Rocı́o (Code: 0600-N-22). The study was conducted in accordance with the local legislation and institutional requirements. Written Informed consent was obtained from all subjects or participants’ legal guardians protected by the GETH-TC.

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Molinos-Quintana, Á., Martínez-Cibrian, N., Alonso-Saladrigues, A. et al. Successful allogeneic CD34+ hematopoietic stem cell boost for prolonged cytopenias following CAR T-cell therapy in B-cell acute lymphoblastic leukemia. On behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC). Bone Marrow Transplant 60, 250–253 (2025). https://doi.org/10.1038/s41409-024-02473-2

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