The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

Abstract

Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

Graft‐versus‐host‐disease does not help acute lymphoblastic leukaemia patients with measurable residual disease

“…Despite the relative inefficacy of donor lymphocyte infusion (DLI) in the treatment of patients with post-transplant acute lymphoblastic leukaemia (ALL) relapses, several findings (such as a lower relapse incidence after allo-HSCT than after autologous stem cell transplantation, lower incidence of relapse in patients with GvHD, or a trend for higher risk of relapse in patients given grafts from syngeneic twins) have suggested potent GvL effects in ALL (Appelbaum, 1997;Stern et al, 2014). This was confirmed by a recent report from the Center for International Blood & Marrow Transplant Research (CIBMTR), which assessed the impact of occurrence of GvHD on allo-HSCT outcomes in a cohort of 5215 patients with ALL who had been given grafts from either a HLA-matched sibling donor, HLA-matched unrelated donor or cord blood transplantation (Yeshurun et al, 2019). In that report, the authors demonstrated that both acute and chronic GvHD protected from ALL relapse.…”

“…However, only a mild form of acute GvHD (grades I-II) translated to improved overall survival (OS) in patients in first or second complete remission (CR) at transplantation. In contrast, chronic GvHD occurrence was associated with better OS in the subgroup of patients with advanced ALL (Yeshurun et al, 2019).…”

Philadelphia Chromosome-Positive Leukemia in the Lymphoid Lineage—Similarities and Differences with the Myeloid Lineage and Specific Vulnerabilities

“…Allo-HSCT with a strong graft vs. host leukemia (GvHL) effect is a very important form of immunotherapy in the treatment of Ph+ B-ALL patients [135]. However, high incidence of treatment-related mortality (up to 40%) and high rates of acute and chronic graft vs. host disease are limiting the widespread use of allo-HSCT [136].…”

The beneficial effects of varicella zoster virus

“…Interestingly, several studies have demonstrated that VZV infection may trigger chronic GVHD following allogeneic HSCT [19][20][21]. GVHD is associated with GVC effects and provided GVHD is of low-grade, it can be associated with improvement in OS in patients with acute leukemia or lymphoma [22][23][24].…”