Role of GVHD/GVL in ALL and immune modulation after transplant to prevent relapse

In a COG trial of transplant for children with ALL, grades I to III acute GVHD were associated with lower relapse risk (HR, 0.4; P = .04) and better EFS (multivariate analysis, HR, 0.5; P = .02). Any effect of grade IV acute GVHD in decreasing relapse risk was obscured by a marked increase in transplant-related mortality (HR, 6.4; P = .003), while grades I to III acute GVHD had no statistically detectable effect on transplant-related mortality (HR, 0.6; P = .42).[136]

In a multivariate model, both pretransplant MRD and acute GVHD were independent predictors of relapse, with the lowest risk of relapse observed in patients with both low pretransplant MRD and grades I to III acute GVHD.[112] For patients who did not develop acute GVHD by day 55 post-HSCT, nearly all relapses occurred between days 100 and 400 post-HSCT.

One study showed that in 46 patients with increasing recipient chimerism, the 31 patients who underwent immune suppression withdrawal, donor lymphocyte infusion, or both therapies had a 3-year EFS rate of 37% versus 0% in the nonintervention group (P < .001).[142]

Other studies have shown better-than-expected rates of survival of pre-HSCT, MRD-positive patients when tapering of immunosuppression medication has occurred for MRD detected after HSCT.[143]

A large international study showed a marked decrease in relapse in patients who experienced MRD-positive disease after HSCT and developed acute GHVD (HR, 0.29; P < .001), resulting in improved EFS (HR, 2.9; P = .01). Acute GVHD significantly decreased relapse and improved EFS in both MRD-positive and MRD-negative patients. Chronic GVHD was also associated with less relapse in both MRD-positive and MRD-negative patients.[92]