A mismatched haplotype may improve outcomes in second BMT

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.

Undergoing a second allogeneic bone or marrow transplant (BMT) is a feasible strategy for patients who have relapsed after their first transplantation, according to findings reported in Biology of Blood and Marrow Transplantation.

Specifically, there may be an advantage to selecting a donor with a new mismatched haplotype after a failed HLA-matched allograft. Among patients who had a second graft transplanted that did not harbor a new mismatched haplotype, median survival was 552 days (95% CI, 376-2,950+). But median survival was not reached in the cohort whose allograft contained a new mismatched haplotype (hazard ratio, 0.36; 95% confidence interval, 0.14-0.9; P = .02).

“In the case of a failed HLA-matched transplantation, when haplotype loss would not be favored through selective pressure and thus would not provide a mechanism of relapse, switching to a different haploidentical donor may be beneficial by increasing major histocompatibility mismatch,” Philip H. Imus, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, and colleagues wrote.

For this retrospective review, the researchers examined 40 consecutive patients who underwent a second BMT for a relapsed hematologic malignancy at a single institution between 2005 and 2014. In all, 21 patients had their first allograft from a haploidentical donor, with 14 of these patients receiving a second haploidentical transplant (8 from a donor sharing the same shared haplotype as the first donor and 6 from a second donor sharing the other haplotype).

The other 19 patients received their first allograft from a fully matched donor, with 14 patients receiving a haploidentical allograft at the second transplantation and 5 receiving a second matched allograft. Overall, a total of 20 patients had a second allograft with a new mismatched haplotype.

The median overall survival for the six patients who were retransplantated with an HLA-haploidentical donor sharing the different haplotype from the first haploidentical donor had not been reached, compared with 502 days (95% CI, 317-2,950+) for the eight patients with a second haplo allograft that shared the same haplotype (HR, 0.37; 95% CI, 0.08 to 1.7; P = .16).

The median event free survival was also superior among those retransplanted with a new mismatched haplotype (not reached vs. 401 days; HR, .50; 95% CI, .22-1.14, P = .09).

A higher risk of mortality was observed in patients who had relapsed within 6 months of their first transplantation (HR, 2.49; 95% CI, 1.0-6.2; P = .07), as well as in those who had progressive or refractory disease prior to their second alloBMT (HR, 2.56; 95% CI, 1.03-6.25; P = .06).

“For patients who relapse more than 6 months after a BMT and who achieve remission with salvage therapy, results are very encouraging,” the researchers wrote. “Although a randomized trial to study selecting donors with a new mismatched haplotype may be impractical, larger numbers should provide additional information on the effectiveness of such an approach.”

The researchers reported having no financial disclosures.

SOURCE: Imus P et al. Biol Blood Marrow Transplant. 2017;23:1887-94.