Relapse rate drives stem cell transplant failure in pediatric ALL patients

Relapse was the main impediment to successful hematopoietic stem cell transplant (HSCT) in high-risk pediatric acute lymphocytic leukemia (ALL), according to one of the largest single-center experiences reported to date.

The effects of relapse were especially evident for patients with haploidentical donors; these patients had a 3-year cumulative relapse incidence of 47% and event-free survival rate of 35%, both significantly higher than what was seen in other transplant recipients treated at the same center.

The findings, recently published in the journal Biology of Blood and Marrow Transplantation, suggest a substantial unmet need in the treatment of high-risk patients in first remission.

“Newer methods to improve graft-versus-leukemia effect are being tested and will need to be incorporated into the management of high-risk patients,” Asaf D. Yanir, MD, and coauthors at Baylor College of Medicine in Houston said in the report.

Dr. Yanir and colleagues reported recent outcomes for 124 patients who had undergone HSCT for ALL at their center during 2008-2016. That group included 20 haploidentical transplant recipients, 48 patients with matched sibling donors, and 56 with unrelated matched donors.

The 3-year cumulative incidence of relapse was 47% for haploidentical recipients, compared with 20% for matched sibling donors recipients and 24% for unrelated matched donors recipients (P = .02), according to their findings.

The main cause of HSCT failure was relapse, occurring in 47% of haploidentical transplant recipients, compared with 20% for those with matched sibling donors and 24% for those with unrelated matched donors (P = .02).

 

Those findings are in line with other studies showing inferior outcomes following haploidentical donor HSCT. However, in contrast to those studies, Dr. Yanir and colleagues did find a rate of treatment-related mortality comparable with other transplant approaches. The 3-year incidence of treatment-related mortality was 15% for the haploidentical group and, similarly, 17% in the matched sibling donor group and 16% in the unrelated matched donor group.

That lower rate of treatment-related mortality in the haploidentical group may be caused by improvements in procedures and supportive care. “Unfortunately, the benefits gained by reducing treatment-related mortality were offset by the high rate of relapse, which remains the main obstacle to successful haploidentical donor HSCT,” Dr. Yanir and coauthors wrote in their report.

New strategies are being studied to retain the graft-versus-leukemia effect or enhance it in patients who’ve undergone haploidentical HSCT, such as selectively depleting alloreactive T cells while sparing other immune effectors, investigators wrote.

“Given evolving practices, it is important to continually evaluate the projected event-free survival for pediatric ALL following HSCT, based on the donor type used,” they wrote.

Dr. Yanir and coauthors had no financial disclosures or conflicts of interest to report.

SOURCE: Yanir AD et al. Biol Blood Marrow Transplant. 2018 Mar 14. doi: 10.1016/j.bbmt.2018.03.001.

Relapse was the main impediment to successful hematopoietic stem cell transplant (HSCT) in high-risk pediatric acute lymphocytic leukemia (ALL), according to one of the largest single-center experiences reported to date.

The effects of relapse were especially evident for patients with haploidentical donors; these patients had a 3-year cumulative relapse incidence of 47% and event-free survival rate of 35%, both significantly higher than what was seen in other transplant recipients treated at the same center.

The findings, recently published in the journal Biology of Blood and Marrow Transplantation, suggest a substantial unmet need in the treatment of high-risk patients in first remission.

“Newer methods to improve graft-versus-leukemia effect are being tested and will need to be incorporated into the management of high-risk patients,” Asaf D. Yanir, MD, and coauthors at Baylor College of Medicine in Houston said in the report.

Dr. Yanir and colleagues reported recent outcomes for 124 patients who had undergone HSCT for ALL at their center during 2008-2016. That group included 20 haploidentical transplant recipients, 48 patients with matched sibling donors, and 56 with unrelated matched donors.

The 3-year cumulative incidence of relapse was 47% for haploidentical recipients, compared with 20% for matched sibling donors recipients and 24% for unrelated matched donors recipients (P = .02), according to their findings.

The main cause of HSCT failure was relapse, occurring in 47% of haploidentical transplant recipients, compared with 20% for those with matched sibling donors and 24% for those with unrelated matched donors (P = .02).

 

Those findings are in line with other studies showing inferior outcomes following haploidentical donor HSCT. However, in contrast to those studies, Dr. Yanir and colleagues did find a rate of treatment-related mortality comparable with other transplant approaches. The 3-year incidence of treatment-related mortality was 15% for the haploidentical group and, similarly, 17% in the matched sibling donor group and 16% in the unrelated matched donor group.

That lower rate of treatment-related mortality in the haploidentical group may be caused by improvements in procedures and supportive care. “Unfortunately, the benefits gained by reducing treatment-related mortality were offset by the high rate of relapse, which remains the main obstacle to successful haploidentical donor HSCT,” Dr. Yanir and coauthors wrote in their report.

New strategies are being studied to retain the graft-versus-leukemia effect or enhance it in patients who’ve undergone haploidentical HSCT, such as selectively depleting alloreactive T cells while sparing other immune effectors, investigators wrote.

“Given evolving practices, it is important to continually evaluate the projected event-free survival for pediatric ALL following HSCT, based on the donor type used,” they wrote.

Dr. Yanir and coauthors had no financial disclosures or conflicts of interest to report.

SOURCE: Yanir AD et al. Biol Blood Marrow Transplant. 2018 Mar 14. doi: 10.1016/j.bbmt.2018.03.001.

Relapse was the main impediment to successful hematopoietic stem cell transplant (HSCT) in high-risk pediatric acute lymphocytic leukemia (ALL), according to one of the largest single-center experiences reported to date.

The effects of relapse were especially evident for patients with haploidentical donors; these patients had a 3-year cumulative relapse incidence of 47% and event-free survival rate of 35%, both significantly higher than what was seen in other transplant recipients treated at the same center.

The findings, recently published in the journal Biology of Blood and Marrow Transplantation, suggest a substantial unmet need in the treatment of high-risk patients in first remission.

“Newer methods to improve graft-versus-leukemia effect are being tested and will need to be incorporated into the management of high-risk patients,” Asaf D. Yanir, MD, and coauthors at Baylor College of Medicine in Houston said in the report.

Dr. Yanir and colleagues reported recent outcomes for 124 patients who had undergone HSCT for ALL at their center during 2008-2016. That group included 20 haploidentical transplant recipients, 48 patients with matched sibling donors, and 56 with unrelated matched donors.

The 3-year cumulative incidence of relapse was 47% for haploidentical recipients, compared with 20% for matched sibling donors recipients and 24% for unrelated matched donors recipients (P = .02), according to their findings.

The main cause of HSCT failure was relapse, occurring in 47% of haploidentical transplant recipients, compared with 20% for those with matched sibling donors and 24% for those with unrelated matched donors (P = .02).

 

Those findings are in line with other studies showing inferior outcomes following haploidentical donor HSCT. However, in contrast to those studies, Dr. Yanir and colleagues did find a rate of treatment-related mortality comparable with other transplant approaches. The 3-year incidence of treatment-related mortality was 15% for the haploidentical group and, similarly, 17% in the matched sibling donor group and 16% in the unrelated matched donor group.

That lower rate of treatment-related mortality in the haploidentical group may be caused by improvements in procedures and supportive care. “Unfortunately, the benefits gained by reducing treatment-related mortality were offset by the high rate of relapse, which remains the main obstacle to successful haploidentical donor HSCT,” Dr. Yanir and coauthors wrote in their report.

New strategies are being studied to retain the graft-versus-leukemia effect or enhance it in patients who’ve undergone haploidentical HSCT, such as selectively depleting alloreactive T cells while sparing other immune effectors, investigators wrote.

“Given evolving practices, it is important to continually evaluate the projected event-free survival for pediatric ALL following HSCT, based on the donor type used,” they wrote.

Dr. Yanir and coauthors had no financial disclosures or conflicts of interest to report.

SOURCE: Yanir AD et al. Biol Blood Marrow Transplant. 2018 Mar 14. doi: 10.1016/j.bbmt.2018.03.001.