Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Abstract

Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678

Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies

“…7, [91][92][93] Of note, different adult ALL study groups applied different cutoff values, depending on the MRD time point and the patient population. NILG used week 16 (cutoff of 1 3 10…”

Challenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults

“…In a study conducted by the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), investigators evaluated the role of HSCT in adults (15-55 years) with ALL treated with a pediatric-inspired regimen and considered to have high-risk disease. 72 There was a lower cumulative incidence of relapse in the HSCT, but higher nonrelapse mortality, leading to similar survival outcomes. However, there did appear to be a benefit with HSCT for patients with poor disease response, defined as residual disease $10 -3 after induction chemotherapy, with a hazard ratio of 0.37 for relapse-free survival (RFS) (95% CI 0.2-0.69; P=0.001) and 0.41 for OS (95% CI 0.22-0.76;…”

“…In fact, two recent studies suggest that HSCT does not benefit young adult patients with ALL who are treated according to pediatric regimens. 71,72 The International Bone Marrow Transplant Registry (IBMTR) conducted a study that compared outcomes for patients 18-50 years of age who were treated with pediatric-inspired chemotherapy regimens or who underwent related or unrelated HSCT. 71 Relapse rates were similar between the groups, but with the higher treatment-related morbidity associated with transplant, and 4-year OS was higher in the group treated with chemotherapy alone (73% [63%-81%] vs 45% [40%-50%], P,0.0001).…”

Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

“…PETHEMA takes a cut off value of 5 × 10 for high-risk patients [12]. However, all these studies highlight the prognostic value of MRD detection in adult patients with ALL.…”

“…MRD has been shown to be prognostic essentially at every time point studied, though the most useful measurements appear to be relatively early in therapy, during or after induction and early in consolidation [12].…”