A large-scale multicenter study of pediatric and adult patients with acute lymphoblastic leukemia (ALL) has confirmed that HCT imparts a potent graft-versus-leukemia effect in ALL with improved survival and lower relapse in patients who experience grade I-II acute GVHD.
Researchers led by Moshe Yeshurun of Rabin Medical Center, Petach-Tikva, Israel, analyzed 5,215 transplants reported to the outcomes database of the CIBMTR® (Center for International Blood and Marrow Transplant Research®). Transplants took place between 2000 and 2014 at 232 centers worldwide.
The researchers examined three cohorts: 1) adults in complete remission (CR1 and 2; n=2,593) treated with myeloablative (MAC) or reduced-intensity conditioning (RIC), 2) pediatric ALL aged 1-18 years in CR1/CR2 (n=1,619) treated by MAC, and 3) patients of all ages with advanced ALL (active disease or CR≥3; n=1,003) who received MAC.
Five-year overall survival (OS) in the 3 cohorts was 45%, 59%, and 27%, respectively. In all 3 cohorts, increased transplant-related-mortality accompanied grade III-IV acute GVHD: HR 3.91, 3.69, 2.69, respectively, compared to reference (no GVHD).
However, adults in CR1/2 with grade I-II acute GVHD (but without any chronic GVHD) had a significantly better 5-year OS compared to recipients who experienced no GVHD (HR 0.83; p=0.025). Children in CR1/CR2 who experienced grade I-II acute GVHD had a similar net survival benefit (HR 0.76; p=0.011). Patients with advanced disease had improved OS if they developed chronic GVHD with or without grade I-II acute GVHD.
In a multivariate analysis, acute GVHD (grades I-II and III-IV) and chronic GVHD were found to be protective of relapse as compared to no GVHD (HR 0.49-0.69) for adult and pediatric patients in CR. The analysis was adjusted for age, white blood cell count, donor source, Karnofsky performance score, GVHD prophylaxis and conditioning.
The researchers concluded that the net beneficial effect of acute GVHD on OS in ALL is confined to patients who experience grade I-II acute GVHD and no chronic GVHD, and that this favorable net effect extends from pediatric to adult patients who are in remission.