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Matched related hematopoietic cell transplant for sickle cell disease with alemtuzumab: the Texas Children’s Hospital experience

Bone Marrow Transplantation volume 56, pages 2797–2803 (2021)Cite this article

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Abstract

Serotherapeutic agents facilitate engraftment and prevent graft-versus-host disease (GVHD) following hematopoietic stem cell transplant. Anti-thymocyte globulin is generally added to conditioning chemotherapy for matched related donor transplant (MRD-HCT) for sickle cell disease (SCD). Alemtuzumab, however, is appealing due to its broad lymphocyte killing that may achieve very low rejection and GVHD rates. To assess the impact of alemtuzumab in MRD-HCT for SCD, we retrospectively reviewed transplant-related outcomes and markers of immunity in 38 consecutive patients at Texas Children’s Hospital having received myeloablative conditioning with alemtuzumab. Median follow-up was 4.8 years (range: 0.2–17). All patients engrafted. Donor chimerism was mixed in 47.1% of patients at ≥2-years. Donor chimerism <50% was uncommon (n = 2). One patient with low myeloid chimerism (19%) had sickle-related hemolysis at 10-years. Incidence of acute GVHD grade II–IV (5.3%) and extensive chronic GVHD (2.8%) was very low. Five-year event-free survival (EFS) and composite chronic GVHD-EFS were excellent at 94.7% (95% CI: 80.3, 98.6) and 89.2% (95% CI: 73.7, 95.8), respectively. Infections did not contribute to mortality although cytomegalovirus reactivation occurred commonly in the first 3 months after transplant. Our data suggest potential for alemtuzumab in myeloablative transplant for children with SCD although further evaluation in older patients and with unrelated donors is warranted.

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Fig. 1: Schematic depicting the conditioning regimen.
Fig. 2: Scatter plot depiction  of donor chimerism by density sorted STR representing myeloid and lymphoid compartments.
Fig. 3: Boxplot representation of absolute lymphocyte counts at 1-year (n = 19).
Fig. 4: 5-year overall and event-free survival, and chronic GVHD, event-free survival  by Kaplan–Meir method.

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Authors and Affiliations

  1. Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Tami D. John, Brian Friend, Khaled Yassine, Ghadir Sasa, Saleh Bhar, Baheyeldin Salem, Bilal Omer, John Craddock, Erin Doherty, Caridad Martinez & Robert A. Krance

  2. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Houston, TX, USA

    Helen E. Heslop

  3. Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA

    Kathryn Leung

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TDJ concept creation, data collection and analysis, manuscript writing. KY, GS, SB, BS, BO, JC, ED, CM manuscript editing. BF, HEH, RAK, KL concept creation, manuscript editing.

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Correspondence to Tami D. John.

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Dr HEH is a co-founder with equity in Allovir and Marker Therapeutics, has served on advisory boards for Gilead, Kiadis, Novartis, Tessa Therapeutics and received research support from Tessa Therapeutics and Kuur Therapeutics.

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John, T.D., Friend, B., Yassine, K. et al. Matched related hematopoietic cell transplant for sickle cell disease with alemtuzumab: the Texas Children’s Hospital experience. Bone Marrow Transplant 56, 2797–2803 (2021). https://doi.org/10.1038/s41409-021-01415-6

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