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Feasibility of early sirolimus cessation post non-myeloablative transplantation in adult patients with severe sickle cell disease

Bone Marrow Transplantation volume 57, pages 319–322 (2022)Cite this article

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Non-myeloablative transplantation (NMA) using alemtuzumab and total body irradiation (TBI) in adult patients with severe sickle cell disease (SCD) is feasible with favorable long term outcomes [1]. Sirolimus is administered as graft vs. host disease (GvHD) prophylaxis frequently resulting in a state of mixed chimerism. It is typically continued for at least 1-year post-transplant with progressive taper initiated when lymphoid chimerism is sustained ≥50% [2]. Such prolonged course of sirolimus can cause undesirable toxicity such as metabolic syndrome, arthralgias, peripheral edema, proteinuria, and secondary malignancies among others [3]. On the other hand, the impact of premature cessation of sirolimus particularly when lymphoid chimerism is low is unknown. Our aim from this analysis is to further examine patients with low or unknown CD3 chimerism that discontinued sirolimus post NMA for severe SCD at our center.

Following IRB approval, adult patients that underwent allogeneic hematopoietic stem cell transplantation (HSCT) from 2015 to 2020 for severe SCD with at least 6 months of follow up post taper (minimum 18 months post HSCT) were included. Conditioning regimen consisted of alemtuzumab (1 mg/kg divided over 5 days on days −7 to −3) and 300 cGy TBI on day −2 or −1 with sirolimus starting on day −1 for GvHD prophylaxis. Peripherally mobilized CD34 cells were infused on day 0 targeting a minimum cell dose of 10 × 106/kg of recipient weight, as feasible. Post-transplant, sirolimus taper began starting at 1 year if lymphoid chimerism is sustained ≥50%, however some patients discontinued earlier due to toxicity or personal preference. Categorical and continuous variables were compared using chi-squared or Kruskal–Wallis, as appropriate.

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Fig. 1: Post-HSCT Hemoglobin.
Fig. 2: Post-HSCT Chimerism.

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Authors and Affiliations

  1. King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia

    Moussab Damlaj, Bader Alahmari, Ahmed Alaskar, Ayman Alhejazi, Husam Alsadi, Inaam Shehab-Eddine, Abdulrahman Alghamdi, Walid Almashaqbeh, Heba Alshobaki, Isam Mahasneh, Ashwaq Alotaibi, Tahany Alanazi, Maybelle Balili, Mohammed Quarshi, Mazin Ahmed & Mohsen Alzahrani

  2. King Abdullah International Medical Research Center, Riyadh, Saudi Arabia

    Moussab Damlaj, Bader Alahmari, Ahmed Alaskar, Ayman Alhejazi & Mohsen Alzahrani

  3. King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

    Moussab Damlaj, Bader Alahmari, Ahmed Alaskar, Ayman Alhejazi & Mohsen Alzahrani

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  1. Moussab Damlaj
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Contributions

MD designed the project, data analysis, data interpretation, and wrote the paper. BA data interpretation and wrote the paper. AAlaskar data interpretation and wrote the paper. AAlhejazi data interpretation and wrote the paper. HAlsadi data interpretation and wrote the paper. ISE data collection and wrote the paper. AAlghamdi data interpretation and wrote the paper. WA data interpretation and wrote the paper. HAlshobaki data interpretation and wrote the paper. IM data interpretation and wrote the paper. AAlotaibi data interpretation and wrote the paper. TA data interpretation and wrote the paper. MB data collection and wrote the paper. MQ data interpretation and wrote the paper. MAhmed data interpretation and wrote the paper. MAlzahrani designed the project, data analysis, data interpretation and wrote the paper.

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Correspondence to Moussab Damlaj.

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Damlaj, M., Alahmari, B., Alaskar, A. et al. Feasibility of early sirolimus cessation post non-myeloablative transplantation in adult patients with severe sickle cell disease. Bone Marrow Transplant 57, 319–322 (2022). https://doi.org/10.1038/s41409-021-01548-8

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