Long-Term Outcomes of Stem-Cell Transplantation for Sickle Cell Disease

David Green, MD, PhD

Nonmyeloablative transplantation ameliorated many clinical manifestations of SCD.

The quality of life for many patients with sickle cell disease (SCD) is dismal because of recurrent hospitalizations for crises, persistent pain, strokes, and cognitive decline. In 2009, NIH investigators reported promising initial results of a phase I and II trial of a nonmyeloablative allogeneic hematopoietic stem-cell transplantation (HSCT) regimen for patients with severe SCD (NEJM JW Oncol Hematol Dec 15 2009). The investigators now report outcomes at a median follow-up of 3.4 years (range, 1.0–8.6).

Donor leukocyte engraftment occurred in 26 of 29 patients (87%); 1 year after HSCT, 25 patients (83%) had full donor-type hemoglobin. A concomitant decline in measures of hemolysis was seen, including significant increases in hemoglobin (11.9 g/dL in women and 12.1 g/dL in men) and decreases in lactate dehydrogenase, bilirubin, and reticulocyte counts (P<0.001 for all comparisons vs. pretransplant values). The level of hemoglobin S (HbS) was 35.3% if the donor had sickle-cell trait versus 0% if the donor had normal hemoglobin.

Following engraftment, mean donor chimerism occurred more rapidly with myeloid cells (CD14 or CD15) than with T-cells (CD3); at a median follow-up of 3.6 years, mean chimerism was 86% for donor myeloid cells and 48% for donor T-cells. Immunosuppression with sirolimus was discontinued after 1 year in 15 patients who achieved 50% CD3 chimerism. Subsequently, the percentage of chimerism, HbS, and total hemoglobin remained stable, and graft-versus-host disease did not develop.

Following successful HSCT, no new strokes occurred, tricuspid regurgitant velocity significantly decreased (P=0.01), and liver-function tests improved. In addition, it became possible to institute phlebotomy for patients with prior iron overload, and ferritin levels fell to <300 ng/mL in seven patients. Overall narcotic usage declined, and six chronic users were successfully weaned from their drugs.

Citation(s):

Hsieh MM et al. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA 2014 Jul 2; 312:48.