The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial

Abstract

The biology and outcome of adult t(4;11)(q21;q23)/MLL-AFF1 acute lymphoblastic leukemia are poorly understood. We describe the outcome and delineate prognostic factors and optimal post-remission therapy in 85 consecutive patients (median age 38 years) treated uniformly in the prospective trial UKALLXII/ECOG2993. The immunophenotype of this leukemia was pro-B (CD10(NEG)). Immaturity was further suggested by high expression of the stem-cell antigens, CD133 and CD135, although CD34 expression was significantly lower than in t(4;11)-negative patients. Complete remission was achieved in 77 (93%) patients but only 35% survived 5 years (95% CI: 25-45%); the relapse rate was 45% (95% CI: 33-58%). Thirty-one patients underwent allogeneic transplantation in first remission (15 sibling donors and 16 unrelated donors): with 5-year survival rates of 56% and 67% respectively, only 2/31 patients relapsed. This compares with a 24% survival rate and 59% relapse rate in 46 patients who received post-remission chemotherapy. A major determinant of outcome was age with 71% of patients aged <25 years surviving. Younger patients had lower relapse rates (19%) but most received allografts in first complete remission. In conclusion, multivariate analysis did not demonstrate an advantage of allografting over chemotherapy but only five younger patients received chemotherapy. Prospective trials are required to determine whether poor outcomes in older patients can be improved by reduced-intensity conditioning allografts. NCT00002514 www.clinicaltrials.gov.

Figures

Figure 1.

Overall survival of 85 adult patients with t(4;11)-positive acute lymphoblastic leukemia (ALL) treated in the UKALLXII/ECOG2993 study.

Figure 2.

Patient flow chart. CRI: first complete remission.

Figure 3.

(A) Relapse rate and survival of 77 adult patients with t(4;11)-positive acute lymphoblastic leukemia (ALL) treated in the UKALLXII/ECOG2993 study by treatment received in first remission. The 15 patients with unrelated donors include one transplanted from a mismatched related donor. (B) Relapse rate and survival of 85 adult patients with t(4;11)-positive acute lymphoblastic leukemia (ALL) treated in the UKALLXII/ECOG2993 study by age.