Non-myeloablative human leukocyte antigen-matched related donor transplantation in sickle cell disease: outcomes from three independent centres.

Abstract

Non-myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim-mobilized peripheral blood HPC and sirolimus. The median follow-up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft-versus-host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle-related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well-tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.

• Authors: Mohsen Alzahrani, Moussab Damlaj, Neal Jeffries, Bader Alahmari, Avani Singh, Damiano Rondelli, John F Tisdale, Santosh L Saraf, Matthew M Hsieh
• Journal: British journal of haematology (Br J Haematol) Vol. 192 Issue 4 Pg. 761-768 (02 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 33534948 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © Published 2020. This article is a U.S Government work and is in the public domain in the USA.

Chemical References

• Antineoplastic Agents, Immunological
• HLA Antigens
• Immunosuppressive Agents
• Alemtuzumab
• Sirolimus

Topics

• Adolescent
• Adult
• Alemtuzumab (therapeutic use)
• Anemia, Sickle Cell (immunology, therapy)
• Antineoplastic Agents, Immunological (therapeutic use)
• Child
• Female
• Graft Rejection (etiology, immunology)
• Graft Survival
• Graft vs Host Disease (etiology, immunology)
• HLA Antigens (immunology)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Sirolimus (therapeutic use)
• Tissue Donors
• Transplantation, Homologous (adverse effects, methods)
• Treatment Outcome
• Young Adult