HLA-Mismatched Microtransplant in Older AML Patients Yields Good Results

HLA-mismatched microtransplant offers good complete remission (CR) rates in older patients with acute myeloid leukemia (AML), according to a new study.

“Older patients (≥ 60 years) with AML have a lower CR rate and higher mortality after standard treatments because of intrinsic drug resistance related to poor-risk cytogenetics, as well as unique biology, with different molecular drivers evidence compared with younger patients,” wrote senior study author Hui-Sheng Ai, MD, of the Affiliated Hospital of the Academy of Military Medical Sciences in Beijing, and colleagues. Earlier studies have shown that infusion of granulocyte colony stimulating factor–mobilized HLA-mismatched peripheral blood stem cells (microtransplant) can improve outcomes.

The new study included 185 patients with AML with a median age of 67 years. They were divided into four age groups: 60 to 64 years (69 patients), 65 to 69 years (47 patients), 70 to 74 years (43 patients), and 75 to 85 years (26 patients). They received HLA-mismatched donor cell infusions and induction chemotherapy, and those that achieved CR received postremission therapy; the results were published in JAMA Oncology.

In the full cohort, the CR rate was 74.6%. The rate did not differ significantly between the 4 age groups, at 75.4%, 70.2%, 79.1%, and 73.1%, respectively. The CR rate was lower in a group of 90 patients considered high risk (66.7%) vs those in the standard-risk group (82.1%; P = .02).

Overall, the median time to neutrophil recovery was 12 days after induction chemotherapy, and the median time to platelet recovery was 14 days; again, there were no differences between the age groups. There were 11 severe infections (8.0% of the 138 patients who achieved CR) and 3 cases of organ failure (2.2%). 

The median overall survival (OS) among those who achieved CR was 14 months; in the 4 age groups, the median OS was 16, 14, 13, and 10 months, respectively. The oldest age group had a 1-year OS rate of 51.7%, which was significantly lower than that of the younger 3 groups (87.7%, P = .004; 85.8%, P = .008); 77.8%, P = .04). The youngest group’s 2-year OS rate of 63.7% was higher than the rates of the older 2 age groups (34.2% and 14.8%).

Only two patients in the study demonstrated stable full donor chimerism, and three had mixed chimerism. Two patients (1.1%) had severe graft-vs-host disease; both failed to respond to treatment and died of multi-organ failure.

The authors wrote that the CR and OS outcomes are better than that seen with standard care in older AML patients. The study is limited by lack of randomization; however, such a study is difficult to conduct, especially in older patients.

“Clinical results suggest that [microtransplant] is a safe, practical, and reproducible therapy in older patients newly diagnosed as having AML,” they concluded.