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. 2022 Dec 9;2022(1):277-282.
doi: 10.1182/hematology.2022000372.

Organ function indications and potential improvements following curative therapy for sickle cell disease

Monica L Hulbert  1 , Allison A King  1 , Shalini Shenoy  1
Affiliations

Organ function indications and potential improvements following curative therapy for sickle cell disease

Monica L Hulbert et al. Hematology Am Soc Hematol Educ Program. .

Abstract

Curative therapies for sickle cell disease include allogeneic hematopoietic stem cell transplantation (HSCT) and gene-modified autologous stem cell transplantation. HSCT has been used for 30 years with success measured by engraftment, symptom control, graft-vs-host disease (GVHD) risk, organ toxicity, and immune reconstitution. While human leukocyte antigen-matched sibling donor (MSD) transplants have excellent outcomes, alternate donor transplants (unrelated/haploidentical) are just beginning to overcome GVHD and engraftment hurdles to match MSD. Gene therapy, a newly developed treatment, is undergoing careful evaluation in many trials with varying approaches. The risk/benefit ratio to the patient in relation to outcomes, toxicities, and mortality risk drives eligibility for curative interventions. Consequently, eligibility criteria for MSD transplants can be less stringent, especially in the young. Posttransplant outcome analysis after the "cure" with respect to organ function recovery is essential. While established damage such as stroke is irreversible, transplant can help stabilize (pulmonary function), prevent further deterioration (stroke), improve (neurocognition), and protect unaffected organs. Tracking organ functions postintervention uniformly between clinical trials and for adequate duration is essential to answer safety and efficacy questions related to curative therapies. Age-appropriate application/outcome analyses of such therapies will be the ultimate goal in overcoming this disease.

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Conflict of interest statement

Monica L. Hulbert is a consultant for Bluebird Bio and Global Blood Therapeutics, has received research funding from Forma Therapeutics and Global Blood Therapeutics, and has family member employment with Pfizer Inc.

Allison A. King has received research funding from Global Blood Therapeutics.

Shalini Shenoy is vice chair on the ASH publications committee, DSMB chair with Aruvant Technologies, a member of NHLBI DSMB, and attended the advisory board meeting for Bristol Myers Squibb.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Expanding transplant indications based on risk/benefit ratio. HLA, human leukocyte antigen; QOL, quality of life; TCD, transcranial Doppler velocity.
See this image and copyright information in PMC

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