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A fludarabine and melphalan reduced-intensity conditioning regimen for HSCT in fifteen chronic granulomatous disease patients and a literature review

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Abstract

Chronic granulomatous disease (CGD) is a life-threatening immunodeficiency condition. To date, hematopoietic stem cell transplantation (HSCT) is the only curative modality. We prospectively studied the outcomes of fifteen CGD patients undergoing HSCT with fludarabine and melphalan plus anti-thymocyte globulin (ATG). Most of the donors were fully matched siblings (n = 12). Cyclosporine A and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. CGD diagnosis had been suspected upon clinical symptoms and was confirmed in all patients by an abnormal neutrophil functional assay. The three-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 46.7%, respectively. With the median follow-up time of 33.12 months, the mean OS and EFS were 42.6 and 26.8 months; respectively. Eleven patients (73.33%) achieved full donor chimerism. Two stable mixed chimerisms with no sign of the underlying disease (13.33%) and two secondary graft failure (13.33%) occurred as well. The cumulative incidence of transplant-related mortality was 23.1% and it was two times more in adults compared with children. Three years GVHD-FS (free survival) was 57.8% in all patients and it was 70% and 42.9% in children and adults, respectively. Our results indicate that fludarabine, melphalan, and ATG have relatively favorable outcomes in CGD patients. Also, we suggest that HSCT should be performed as soon as a suitably matched donor is found.

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Acknowledgements

We would like to thank the transplantation ward’s staff of Shariati Hospital and Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Vaezi, Maryam Souri, Seyed Amin Setarehdan, Kamran Alimoghaddam & Ardeshir Ghavamzadeh

  2. Department of Pediatric Hematology and Oncology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Amir Ali Hamidieh

  3. Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Amir Ali Hamidieh

  4. Immunology, Asthma and Allergy Research Institute, Children’s Medical Center Hospital, Tehran University of Medical Sciences, No. 62, Dr. Gharib Street, Keshavarz Blvd, 14194, Tehran, Iran

    Mohammad Reza Fazlollahi, Zahra Pourpak, Mohsen Badalzadeh & Shaghayegh Tajik

  5. Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Alireza Mahdaviani

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  1. Mohammad Vaezi
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Correspondence to Mohammad Reza Fazlollahi.

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Vaezi, M., Souri, M., Setarehdan, S.A. et al. A fludarabine and melphalan reduced-intensity conditioning regimen for HSCT in fifteen chronic granulomatous disease patients and a literature review. Ann Hematol 101, 869–880 (2022). https://doi.org/10.1007/s00277-022-04751-9

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