Development of low-grade acute graft-versus-host disease (aGVHD) lowers relapse risk and positively affects overall survival (OS) for patients with acute lymphoblastic leukemia (ALL) in complete remission one and two (CR1/CR2). That’s the conclusion of researchers who aimed to better understand the graft-versus-leukemia (GVL) effect in patients with ALL, and how disease stage and severity of GVHD impacts hematopoietic cell transplant (HCT) outcomes.
The retrospective study included 5,215 HCT recipients with ALL who had data in the CIBMTR® (Center for International Blood and Marrow Transplant Research®) registry. Three cohorts were created for the analysis: adults in CR1 or CR2, pediatric patients in CR1 or CR2, and adults and children in ≥CR3 or active disease ALL. Outcomes analysis included: non-relapse mortality (NRM), relapse and overall survival. (See results in the chart below.)
Patients with grades I and II aGHVD without cGVHD who received HCT in CR1 or CR2 experienced a 17-24 percent lower risk of mortality than patients who did not experience GVHD. For patients in CR1 or CR2, both aGVHD and cGVHD were protective against relapse (HR, 0.49 - 0.69). Having grade III or IV versus a mild grade I or II GVHD was not more protective against relapse.
For patients with advanced stage ALL, the presence of cGVHD lowered the risk for overall mortality by 27-32 percent. Improved OS in this cohort (HR, 0.69-0.73) was associated with the development of cGVHD and with or without mild stage aGVHD. However, in all cohorts grades III and IV aGVHD and cGVHD were associated with higher NRM and decreased OS despite lower relapse rates.
Researchers found adults (45 percent) and children (59 percent) who received HCT in CR1 or CR2 experienced improved five-year survival compared to those who received HCT in an advanced/active disease stage (27 percent). These findings support additional study results showing that HCT in earlier disease stage strongly impacts survival.
Adults in CR1/CR2 (age 18-75 at HCT) | Children in CR1/CR2 (age 1-18 at HCT) | Adults and children with advanced (CR≥3 or active) disease(age 1-67) | |
| Patients (n) | 2,593 | 1,619 | 1,003 |
| aGVHD - Grade I, II by day 100 | 41% | 42% | 42% |
| aGVHD - Grade III, IV by day 100 | 18% | 19% | 23% |
| cGVHD at one year | 46% | 29% | 29% |
| No GVHD | 22% | 30% | 27% |
| One-year relapse | 21% | 20% | 36% |
| Five-year relapse | 32% | 30% | 44% |
| One-year NRM | 20% | 14% | 26% |
| Five-year NRM | 29% | 17% | 32% |
| One-year overall survival | 68% | 73% | 47% |
| Five-year overall survival | 45% | 59% | 27% |
Yeshurun M, et al., Blood Advances