At three years, patients with acute lymphoblastic leukaemia are still at risk for relapse. Results of the international MRC UKALLXII/ECOG E2993 trial

Abstract

Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43Á2%) relapsed; 691 (91Á3%) within three years and 66 (8Á7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3Á8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11Á7% underwent autologous and 40Á6% allogeneic transplant, while in CR1. Of the autologous patients, 43Á2% relapsed early and 3Á4% relapsed late. However, among the allogeneic patients, 13Á2% relapsed early and only 1Á3% late. The five-year overall survival from relapse was 5Á8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.

Late and very late relapsed acute lymphoblastic leukemia: clinical and molecular features, and treatment outcomes

“…Acute lymphoblastic leukemia (ALL) often relapse early after the treatment course, within the first two years from the initial diagnosis [ 1 – 3 ]. Cases of late relapse (LR) occurring in ≥5 years from initial diagnosis have been reported infrequently [ 4 – 6 ]. However, there is no exact definition for late/very late relapse of ALL.…”

“…Vora et al, reported 12 cases (~1%) with very-late relapse (VLR), defined as >10 years from the time of complete remission (CR), among 1134 children treated on the Medical Research Council (MRC) ALL trials [ 5 ]. The MRC UKALLXII/ECOG E2993 reported that 2.8% ( n = 21) of all relapses in adult ALL patients were late (≥5 years from remission) [ 6 ]. Rizzari et al showed that LR ALL (≥5 years) occurred in 2.9% of Italian children, with a median onset of 6.1 years (range: 5.8–13.7) [ 4 ].…”

Alternative RNA Splicing—The Trojan Horse of Cancer Cells in Chemotherapy

“…Hematologic malignancies account for 6–10% of all cancers and encompass a large group of blood neoplasms including different types of lymphoma, multiple myeloma, as well as myeloid and lymphoid leukemia [ 50 , 187 ]. The prognosis in this heterogeneous group of diseases ranges from nearly 90% overall survival rates in acute promyelocytic leukemia [ 188 ] to less than 6% after early relapse of acute lymphoblastic leukemia [ 189 ]. While there are certain recurrent genetic mutations in leukemia, hematologic malignancies remain largely heterogenic.…”

Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy‐refractory or relapsed disease prior to allogeneic stem cell transplantation

“…Patients with acute lymphoblastic leukaemia (ALL), characterized by the monoclonal proliferation of immature cells in the lymphoid lineage, 1 often respond to the induction chemotherapies and >80% of adult ALL patients can achieve complete haematological response (CR). 2 However, the relapse rate ranges from 44% to 50% after the initial remission status, [3][4][5] and this is related to non-optimal overall survival (OS). [6][7][8] One of the treatment options for such chemotherapyrefractory or relapsed (r/r) ALL is allogeneic haematopoietic stem cell transplantation (allo-HSCT).…”