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Haploidentical stem cell transplantation cures autoimmune hepatitis and cerebrovascular disease in a patient with sickle cell disease

Bone Marrow Transplantation volume 53, pages 644–646 (2018)Cite this article

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Sickle Cell Disease (SCD) may lead to several acute and chronic complications and the end-organ damage may be aggravated by co-existing conditions. [1] Among SCD patients, autoimmune disorders, such as autoimmune hepatitis (AIH) or systemic lupus erythematosus, are not infrequent and are difficult to treat due to the high risk of adverse events associated with steroids or other immunosuppressive treatments. [2–4] Hematopoietic Stem Cell Transplantation (HSCT) is the most consolidated curative therapy for patients with SCD, but benefits and risks in both the short and long term must be carefully considered, taking into consideration disease variability and the recent appearance of new drugs. Despite the progressive broadening of indications for HSCT, [5] the majority of pediatric haematologists still offers it only to patients with a severe phenotype: cerebrovascular disease, recurrent vaso-occlusive crises (VOC) or acute chest syndrome not responsive to Hydroxycarbamide, or sickle nephropathy. [6, 7] HSCT is also an option for the management of severe autoimmune disorders such as multiple sclerosis, systemic sclerosis and rheumatoid arthritis, but it has not been previously reported for autoimmune hepatitis. [8] We report a patient with SCD and AIH, both cured after HSCT.

At the age of 16 years, the patient underwent a HSCT after conditioning with Treosulfan, Fludarabine, Thiotepa, Rituximab and Graphalon® anti-thymocyte globulins. The intensive transfusion program required to control the cerebrovascular disease as well as the recurrent VOCs constituted the main indication for HSCT. Due to the lack of a matched sibling donor or a matched unrelated donor, her HbSA haploidentical father was employed as a donor and an ex-vivo TCRαβ and CD19 depletion on PBSC (peripheral blood stem cell) was performed. [9] The regimen-related toxicity included grade 4 thrombocytopenia, grade 3 anemia, grade 3 febrile neutropenia and grade 3 mucositis, all resolving completely. No post-transplant immune suppression was given and all treatments for AIH were interrupted before the beginning of conditioning. On day +35 post HSCT, the patient presented with fever, abdominal pain and anorexia; a gastric and rectal biopsy showed hystological signs of Graft-versus-Host disease (GvHD) and the patient was diagnosed with grade II acute GvHD. She received treatment with cyclosporine and extracorporeal photochemotherapy, which resulted in complete remission of symptoms within one week. Cyclosporine was continued for one month and extracorporeal photochemotherapy for 4 months. At two years post-HSCT, chimerism analysis showed a full donor hematopoiesis, no SCD manifestation occurred, cerebral vasculopathy resolved almost completely (Fig. 1b) and the patient was without any medical treatment. The patient did not experience any relapse of AIH and anti-nuclear and anti-smooth muscle autoantibodies were found negative two months after HSCT and thereafter.

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Acknowledgements

EC, AM, MC, SR, MT, GB, LS and RC were involved in the clinical management of the patient, MP and MR performed and reviewed the histological examination, RM performed the neuroimaging, AM wrote the paper, and EC, MC, RC and LS critically reviewed the paper. The authors would like to thank Chiara Messina, Marta Pillon, Chiara Mainardi and Maria Gabelli for their participation in the clinical management of the patient. This project was performed thanks to a Grant from Fondazione Città della Speranza ONLUS (16/04).

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    Authors and Affiliations

    1. Pediatric Hematology-Oncology Unit, Department of Women’s and Children’s Health, Azienda Ospedaliera-University of Padova, Padova, Italy

      Elisabetta Calore, Antonio Marzollo, Sara Rossin, Manuela Tumino, Giuseppe Basso, Raffaella Colombatti & Laura Sainati

    2. Pediatric Gastroenterology and Hepatology Unit, Department of Women’s and Children’s Health, Azienda Ospedaliera-University of Padova, Padova, Italy

      Mara Cananzi

    3. General Pathology and Cytopathology Unit, Department of Medicine—DIMED, Azienda Ospedaliera-University of Padova, Padova, Italy

      Marco Pizzi & Massimo Rugge

    4. Neuroradiology Unit, University of Salerno, Salerno, Italy

      Renzo Manara

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    Correspondence to Antonio Marzollo.

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    Raffaella Colombatti and Laura Sainati contributed equally to the work.

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    Calore, E., Marzollo, A., Cananzi, M. et al. Haploidentical stem cell transplantation cures autoimmune hepatitis and cerebrovascular disease in a patient with sickle cell disease. Bone Marrow Transplant 53, 644–646 (2018). https://doi.org/10.1038/s41409-017-0065-5

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