Patients with high-risk sickle cell disease had significantly improved health-related quality of life (QOL) and remained stable or saw improvement in other outcomes of interest, including neurocognitive outcomes, after undergoing myeloablative conditioning (MAC) and parental haploidentical stem cell transplantation (HISCT) with CD34 enrichment and mononuclear cell addback, according to results of a study presented at the 60th Annual ASH Meeting and Exposition.
With a median follow-up of more than 3 years, there have been no recurrences of sickle cell pain crises, no patients have required blood transfusion, and no new patients have developed graft-versus-host disease, according to study researcher Mitchel Cairo, MD, of New York Medical College, Valhalla, N.Y.
“These individuals have a completely new lease on life,” Cairo said in a prepared statement. “They’re either stable or better in every organ system. What’s more, this could mean that every person with sickle cell disease who has a living parent could have a potential donor in their family.”
According to the study, the only cure for sickle cell disease is HLA-matched sibling allogeneic stem cell transplantation after either MAC or reduced toxicity conditioning. However, only a small percentage of patients have an unaffected HLA-matched sibling donor.
This study was designed to look at long-term outcomes of transplant from parental donors, who have only 50% matched bone marrow. During the transplant the bone marrow is enriched with CD34 protein that promotes the acceptance of transplanted blood-forming cells. In addition, the researchers added back the patients’ T cells after transplant (mononuclear cell addback)
In the study, patients with sickle cell disease and one or more high-risk features underwent MAC and parental HISCT using CD34 enrichment and mononuclear cell addback with tacrolimus acute graft-versus-host disease prophylaxis. Outcome measures were performed at baseline and 2 years post-transplant.
Nineteen patients underwent transplant at a mean age of 13.1; the 18 parental HLA-matched donors had a mean age of 41.3. The 1-year mean whole white blood cell and red blood cell mixed donor chimerism was 97.1% and 96.4%, respectively, constituting long-term stability.
At 2 years, transplant recipients had significantly improved processing speed (P<.026). There were also improvements in both emotional functioning (P<.03) and physical functioning (P<.01) at 2 years compared with baseline. Intellectual functioning, memory, language, and executive function were all stable or improved.
The probability of 1 year event-free survival was 90%. Recipients either remained stable or saw improvements on pulmonary function tests (P<.026) and cardiac SF and TRJ velocity. Imaging follow-up showed no new overt and/or silent strokes and no new cerebral vasculopathy. The incidence of grade 2-4 acute and chronic graft versus host disease was 6.2% and 6.7%, respectively.
In discussing the results, Cairo cautions that the procedure is not successful in all patients, adding that whether patients will develop late adverse effects is not yet known.
Cairo M, et al. Significantly improved long term health related quality of life (HRQOL) and neurocognition following familial haploidentical stem cell transplantation (HISCT) utilizing CD34 enrichment and mononuclear (CD3) addback in high risk patients with sickle cell disease (SCD). Presented at 60th Annual ASH Meeting and Exposition; December 1-4, 2018; San Diego. Abstract #162.