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Durable engraftment after pharmacological pre-transplant immune suppression followed by reduced-toxicity myeloablative haploidentical stem cell transplantation in highly HLA-immunized adults with sickle cell disease

Bone Marrow Transplantation volume 59, pages 918–927 (2024)Cite this article

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Abstract

Allogeneic stem cell transplantation (Allo-SCT) is the only rapidly available curative treatment modality in patients with severe sickle cell disease (SCD). The development of reduced-toxicity myeloablative conditioning (RT-MAC) regimen and the use of partially matched family donors with post-transplantation cyclophosphamide (PT-Cy) have widened the access to Allo-SCT. Antibodies against donor-specific HLA (DSA) increase the risk of engraftment failure in HLA mismatched Allo-SCT. We report the results of five patients with SCD, whereas three with DSA, who underwent an unmanipulated haploidentical stem cell transplantation (Haplo-SCT) after a busulfan-based RT-MAC regimen with PT-Cy. To reduce the risk of engraftment failure, a sequential two courses pharmacological pre-transplant immune suppression (PTIS) phase was added prior to the conditioning regimen. All patients engrafted successfully. The procedure was well tolerated. None of the patients developed acute GVHD, whereas one developed moderate chronic GVHD. After a median follow-up of 5 years (range, 2.2–9), all patients are free of pain with excellent quality of life. Our report shows that Haplo-SCT after a RT-MAC regimen is feasible and safe with stable long-term engraftment and excellent disease control. The risk of graft failure can be abrogated by adding a PTIS phase prior to initiating the conditioning regimen.

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Fig. 1: Pharmacological pre-transplant immune suppression (PTIS).
Fig. 2: Reduced-toxicity myeloablative conditioning regimen (RT-MAC).
Fig. 3: Hemoglobin S and chimerism patient 1.
Fig. 4: Hemoglobin S and chimerism patient 2.
Fig. 5: Hemoglobin S and chimerism patient 3.
Fig. 6: Hemoglobin S and chimerism patient 4.
Fig. 7: Hemoglobin S and chimerism patient 5.

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Data are available on request from the corresponding author.

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Acknowledgements

We thank the patients and their family, and the IPC transplant team.

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Authors and Affiliations

  1. Department of Hematology, Institut Paoli Calmettes, Marseille, France

    Sabine Fürst, Faezeh Legrand, Angela Granata, Samia Harbi, Valerio Maisano, Benjamin Bouchacourt & Thomas Pagliardini

  2. Reference Center for Sickle Cell Disease, Thalassemia and Other Red Cell Rare Diseases, CHU Guadeloupe, Pointe à Pitre, Guadelloupe, France

    Emmanuelle Bernit

  3. Department of Hematology, Institut Paoli Calmettes, Centre de Recherche en Cancérologie de Marseille, INSERM, CNRS, Aix-Marseille University, Marseille, France

    Raynier Devillier & Didier Blaise

  4. Department of Intensive Care, Institut Paoli Calmettes, Marseille, France

    Djamel Mokart

  5. Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France

    Claude Lemarié & Boris Calmels

  6. HLA Laboratory, Etablissement Français du Sang, Marseille, France

    Christophe Picard & Agnès Basire

  7. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Borje S. Andersson

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SF designed and wrote the manuscript. BSA and DB provided substantial support and revised the manuscript. All authors edited the manuscript and approved its submission.

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Correspondence to Sabine Fürst.

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BSA is a consultant for RACE Oncology, Ltd., and member of the Board of reenJay Therapeutics, Inc.

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Fürst, S., Bernit, E., Legrand, F. et al. Durable engraftment after pharmacological pre-transplant immune suppression followed by reduced-toxicity myeloablative haploidentical stem cell transplantation in highly HLA-immunized adults with sickle cell disease. Bone Marrow Transplant 59, 918–927 (2024). https://doi.org/10.1038/s41409-024-02257-8

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