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Lymphocyte infusion, second stem cell transplant offer comparable OS for relapsed acute myeloid leukemia

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August 30, 2018

Survival appeared comparable following a second allogeneic hematopoietic stem cell transplant or donor lymphocyte infusion among patients with acute myeloid leukemia who relapsed after first HSCT, according to results of a retrospective registry study.

However, two characteristics appeared associated with improved survival following either second HSCT or donor lymphocyte infusion: attaining a complete remission prior to salvage therapy, and longer time to relapse after first HSCT.

“To our knowledge, these results represent the largest study comparing outcomes of patients treated with either a [second] allogeneic hematopoietic cell transplant or donor lymphocyte infusion after AML relapse of a prior allogeneic hematopoietic cell transplant,” Mohamed A. Kharfan-Dabaja, MD, MBA, oncologist in the division of hematology and oncology at Mayo Clinic in Jacksonville, Florida, and colleagues wrote.

Treatment options for relapsed AML after an allogeneic HSCT “remain elusive,” according to the researchers.

Patients who experience significant toxicity and adverse events from the first allogeneic HSCT are typically offered supportive care, whereas other eligible patients may receive more intense care, such as a second allogeneic HSCT or donor lymphocyte infusion. However, no randomized clinical trial has compared survival outcomes of a second HSCT vs. donor lymphocyte infusion.

“The decision to offer either option is based on several factors, including donor availability, remission status, presence of disabling comorbidities, and center or physician preference,” researchers wrote.

Kharfan-Dabaja and colleagues used data from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry study to compare OS after a second allogeneic HSCT or one or more donor lymphocyte infusions among 418 patients (mean age, 46.2 years; 54.5% men) with relapsed AML after first allogeneic HSCT.

A total 137 patients (median age, 43 years) underwent second allogeneic HSCT and 281 patients (median age, 49 years) underwent donor lymphocyte infusion.

Patients who underwent second allogeneic HSCT appeared less likely to receive treatment from the original donor (59.8% vs. 100%; P < .001) and had a higher incidence of remission at the time of intervention (38.7% vs. 18.1%; P < .001). Relapsed occurred later among patients who underwent second HSCT (348 days vs. 211 days; P = .004) and, thus, they received therapy later (71 day vs. 30 days; P < .001).

The number of patients alive after 2 years and 5 years from receiving a second allogeneic HSCT or donor lymphocyte infusion served as the study’s primary outcomes.

Median follow-up from intervention for surviving patients was 63 months (range, 1-157).

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Results showed similar OS between the second allogeneic HSCT and donor lymphocyte infusion groups at 2 years (26% vs. 25%) and 5 years (19% vs. 15%).

Patients who reached complete remission at the time of the intervention had better OS with either procedure (HR = 0.55; 95% CI, 0.41-0.74).

However, patients who relapsed less than 6 months after first allogeneic HSCT had poor OS, regardless of the treatment prescribed. Among these patients, 5-year OS was 9% (95% CI, 1-17) with second allogeneic HSCT and 4% (95% CI, 1-8) with donor lymphocyte infusion.

Conversely, 5-year OS among patients who relapsed 6 months or more after first HSCT was 24% (95% CI, 14-33) following second HSCT and 23% (95% CI, 16-30) following donor lymphocyte infusion.

Overall, longer time to relapse was associated with improved OS (HR = 0.99; 95% CI, 0.98-0.99).

“[A second] allogeneic hematopoietic cell transplant and donor lymphocyte infusion yielded comparable OS when patients were selected based on our current knowledge,” researchers wrote.

“The heterogeneity of patient-, disease- and treatment-related characteristics limits our ability to recommend one approach over another,” they added. – by Melinda Stevens

Disclosures: Kharfan-Dabaja reports speakers bureau or advisory roles with Alexion Pharmaceuticals, Incyte Corp., Pharmacyclics and Seattle Genetics. Please see the study for all other authors’ relevant financial disclosures.

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