Stem cell transplant may be feasible for young SCD patients

Transplant linked to fewer pain crises, less fatigue than standard care

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A hematopoietic stem cell transplant (HCT) may be a feasible treatment option for adolescents and adults with severe sickle cell disease (SCD), according to a U.S. study.

Two-year survival rates were similar among patients who had an available donor for HCT and among those who did not, although they were not statistically compared. HCT was associated with fewer vaso-occlusive crises (VOCs) and less fatigue relative to standard care.

Overall, “results of this trial following a descriptive analysis supports the notion that HCT … is a suitable treatment option in adolescents and young adults with severe SCD,” researchers wrote. “The choice to pursue a curative treatment is the patient’s decision and the findings of this trial extend generalizable knowledge for informed decision-making.”

The study, “Hematopoietic Cell Transplant compared with Standard Care in Adolescents and Young Adults with Sickle Cell Disease,” was published in Blood Advances.

In SCD, genetic mutations give rise to abnormally shaped red blood cells that cannot move properly through blood vessels. Patients experience recurrent pain episodes called VOCs, among other symptoms.

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Standard treatments help reduce frequency, severity of pain episodes

Standard treatments are generally meant to ease the frequency and severity of these pain episodes.

HCT, more simply referred to as a stem cell transplant, is a potentially curative treatment that’s sometimes used for patients with severe SCD for whom standard treatments failed to keep the disease under control.

Hematopoietic stem cells can give rise to all types of blood cells. A stem cell transplant usually involves collecting these cells from a healthy donor and transplanting them to an SCD patient. The goal is to repopulate the patient’s bone marrow with donor stem cells that are capable of producing healthy red blood cells. Before the transplant, patients usually undergo chemotherapy and/or radiation to destroy the stem cells already in their bone marrow to make room for the new ones.

Data in children with SCD indicate stem cell transplants are associated with a long-term survival benefit. However, the benefits of the procedure in older patients, especially given the risks associated with it, are not as well-established.

The Phase 2 STRIDE2 study (NCT02766465) was designed to evaluate whether a stem cell transplant was associated with a survival benefit relative to standard care in adolescents and young adults with SCD in the U.S.

To receive a stem cell transplant, SCD patients must have a suitable donor who matched them in specific immune markers called human leukocyte antigens, or HLA.

A total of 113 patients, ages 15-40, with severe SCD were enrolled in the study before knowing whether or not they had an HLA-matched donor available. A suitable donor was subsequently found for 28 people (donor group), 24 of whom ultimately underwent the transplant. The remaining 85 people did not have a donor available and received standard care (no donor group).

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Not enough participants for statistical analysis

Low patient recruitment and a lower-than-expected proportion of patients with an HLA-matched donor had caused trial investigators to close it early. As such, the researchers indicated there were not enough participants to power a statistical analysis comparing survival as originally planned, so they performed a descriptive analysis instead.

At two years after group assignment, the overall estimated survival was 89% among those in the donor group and 93% in the standard care group.

There were a total of eight deaths during the two-year period, including five in the standard care arm and three in the donor arm.

Patients in the no donor group experienced significantly more VOCs in the first year than those in the donor arm — a difference that grew larger in the second year, “suggesting that [standard care] was not as effective as HCT in eliminating severe VOC,” the researchers wrote.

Moreover, data indicated benefits in terms of fatigue and ability to participate in social activities for those in the donor arm relative to the no donor group.

Of the 24 people who ultimately underwent a stem cell transplant, three experienced a secondary graft failure, where the transplanted stem cells initially take hold but are lost later, resulting in one death.

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Graft-versus-host disease possible transplant complication

Graft-versus-host disease (GVHD), another possible transplant complication where the donor cells recognize the patient’s body as foreign and start attacking it, was the cause of death for one person.

Nine people developed acute GVHD, which usually occurs in the first 100 days after the transplant, and 11 people developed chronic GVHD, which occurs later.

Overall, the researchers believe the findings support the notion that HCT is a feasible option for adolescents and young adults with severe SCD.

Research indicates that the number of deaths after a stem cell transplant tend to plateau over time, whereas deaths in those treated with standard care may increase. As such, “we hypothesize that longer follow up … is likely to result in a survival advantage for the donor arm,” the researchers wrote.