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Curative allogeneic hematopoietic stem cell transplantation following reduced toxicity conditioning in adults with primary immunodeficiency

Bone Marrow Transplantation volume 57, pages 1520–1530 (2022)Cite this article

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Abstract

Primary immunodeficiencies (PID) are heterogeneous inborn errors of the immune system. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative and safe at the pediatric age but remains underperformed in adults. We report our experience on 32 consecutive adult patients with various PID including 17 (53%) with a combined immune deficiency, six (19%) with a disease of immune dysregulation and nine (28%) with a chronic granulomatous disease (CGD) who underwent an allo-HSCT between 2011 and 2020. The median age at transplant was 27 years (17–41). All assessable patients engrafted. The majority of patients received a fludarabine-Busulfan (FB) based regimen (FB2-3 in 16, FB4 in 12). Overall survival (OS) was 80.4% (100% for CGD and 74% for other PID patients) at 9 months and beyond (median follow-up 51.6 months). Six patients died, all in the first-year post-transplant. Cumulative incidences of grade II–IV acute GVHD/chronic GVHD were 18%/22%. Stem cell source, GVHD prophylaxis and conditioning intensity had no impact on OS. All surviving patients had over 90% donor chimerism, immune reconstitution, no sign of active PID related complications and were clinically improved. Allo-HSCT is effective in young adults PID patients with an acceptable toxicity and should be discussed in case of life-threatening PID.

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Fig. 1: Acute GVHD, Chronic GVHD, Overall survival and GRFS in the whole cohort.
Fig. 2: Acute GVHD, Chronic GVHD, Overall survival and GRFS according to PID subtype.
Fig. 3: Acute GVHD, Chronic GVHD, Overall survival and GRFS according to Busulfan dosage (n = 28).
Fig. 4: Immune reconstitution.

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Correspondence and requests for materials should be addressed to Ambroise Marçais or Felipe Suarez.

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Authors and Affiliations

  1. Service d’Hématologie Adultes, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Université Paris Cité, Paris, France

    Ambroise Marçais, Morgane Cheminant, Olivier Hermine & Felipe Suarez

  2. Laboratoire d’onco-hématologie, Institut Necker-Enfants Malades, INSERM U1151, Université Paris Cité, Paris, France

    Ambroise Marçais & Vahid Asnafi

  3. Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Institut Imagine, Paris, France

    Nizar Mahlaoui & Alain Fischer

  4. Service d’immuno-hématologie pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Université Paris Cité, Paris, France

    Bénédicte Neven, Despina Moshous & Alain Fischer

  5. Service de Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker-Pasteur, Assistance Publique-Hôpitaux de Paris, IHU Imagine, Hôpital Necker Enfants Malades, Université Paris Cité, Paris, France

    Fanny Lanternier & Olivier Lortholary

  6. Service de pneumologie, Hôpital Foch, Suresnes, France

    Émilie Catherinot, Hélène Salvator & Louis-Jean Couderc

  7. Laboratoire d’immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Université Paris Cité, Paris, France

    Maxime Jeljeli

  8. Laboratoire immunologie, INSERM, U1151, 75015, Université Paris Cité, Paris, France

    Peter van Endert

  9. Centre d’études des Déficits Immunitaires, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Institut Imagine, Paris, France

    Capucine Picard

Authors
  1. Ambroise Marçais
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  2. Nizar Mahlaoui
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  3. Bénédicte Neven
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  11. Louis-Jean Couderc
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  15. Olivier Hermine
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  16. Alain Fischer
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  17. Felipe Suarez
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Contributions

AM and FS designed and supervised the study and wrote the manuscript. AM, NM, BN, FL, EC, HS, MC, LJC, OL, CP, DM, OH and AF provided clinical care for the patients included in the study. MJ performed post-vaccination serological assays. VA performed chimerism analysis. PvE performed HLA typing and donor selection and CP performed genetic analysis and immunological cellular reconstitution.

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Correspondence to Ambroise Marçais or Felipe Suarez.

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Marçais, A., Mahlaoui, N., Neven, B. et al. Curative allogeneic hematopoietic stem cell transplantation following reduced toxicity conditioning in adults with primary immunodeficiency. Bone Marrow Transplant 57, 1520–1530 (2022). https://doi.org/10.1038/s41409-022-01739-x

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