Updated risk-oriented strategy for acute lymphoblastic leukemia in adult patients 18–65 years: NILG ALL 10/07

Abstract

An updated strategy combining pediatric-based chemotherapy with risk-oriented allogeneic hematopoietic cell transplantation (HCT) was evaluated in Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) and compared with a published control series. Following induction–consolidation chemotherapy, responsive patients were assigned to receive maintenance chemotherapy or undergo early HCT according to the risk stratification criteria and minimal residual disease (MRD) status. Of the 203 study patients (median age 41 years, range 17–67), 140/161 with Ph− ALL achieved complete remission (86.9%; 91.6% ≤55 years, P = 0.0002), with complete MRD clearing in 68/109; 55 patients were assigned to maintenance chemotherapy, and 85 to HCT due to very high-risk characteristics (hyperleukocytosis, adverse genetics, early/mature T-precursor ALL, and MRD persistence). The 5-year relapse incidence was 36%, and the treatment-related mortality rate was 18%. Median overall and relapse-free survival were 7.4 and 6.2 years, with rates of 54 and 53% at 5 years, respectively, which were significantly better than those obtained with the historical protocol (P = 0.001 and P = 0.005, respectively), without significant differences between maintenance and HCT cohorts. In prognostic analysis, MRD negativity and age ≤55 years were the most favorable independent prognostic factors. A reduction in treatment toxicity and further improvements in the risk definitions and risk-oriented design are the focuses of this ongoing research.

Targeting Telomere Biology in Acute Lymphoblastic Leukemia

“…For the adult cohort, patients ≥ 18 years with a diagnosis of B-ALL before the start of therapy were included. Classification into risk groups was based on hematologic parameters, immunophenotype, (cyto)genetics, and treatment response [4,17].…”

“…Recently, a number of genomic studies have facilitated the further subclassification of pediatric and adult acute lymphoblastic leukemia (ALL) and provided deeper insight into the interplay of genetic alterations and their possible role in disease pathogenesis [1,2]. Some of these alterations bear significant implications for the diagnosis, risk stratification, and therapeutic approach of childhood and adult ALL [3,4]. However, early identification of patients with high-risk disease allowing timely treatment adaption remains challenging.…”

Real-World Multicenter Experience in Tumor Debulking Prior to Blinatumomab Administration in Adult Patients With Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

“…B-cell precursor (BCP) acute lymphoblastic leukemia (B-ALL) accounts for almost 75% of all cases of adult ALL ( 1 ). Despite significant improvements in the management of B-ALL patients in the last decades, the long-term survival for adults is still around 50% ( 2 ). In fact, even though the proportion of adult patients achieving a first complete remission with frontline treatment is 80-90%, about half of them subsequently relapse ( 3 ).…”

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

“…The issue of Peg-ASP dosing and toxicity is highly critical in patients at older age [ 52 , 53 ]. Contrary to younger patients, it appears difficult to demonstrate an advantage by pediatric-type regimens in patients older than 55 years [ 44 , 47 , 51 ]. Non-AYA patients become progressively less tolerant to intensive treatment and display a higher incidence and severity of toxic side effects.…”