Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: Final results of the PETHEMA ALL-AR-03 trial
Ribera J.-M.,Institute Catala dOncologia Hospital Germans Trias i Pujol |
Oriol A.,Institute Catala dOncologia Hospital Germans Trias i Pujol |
Morgades M.,Institute Catala dOncologia Hospital Germans Trias i Pujol |
Montesinos P.,Hospital Universitario La Paz |
And 21 more authors.
Journal of Clinical Oncology
Purpose: Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. Patients and Methods: Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 ×10-4 at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10-4. Results: Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10-3 after induction and ≥ 5 × 10-4 after early consolidation) as the only prognostic factor for DFS and OS. Conclusion: Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS. © 2014 by American Society of Clinical Oncology. Source
Kelleher N.,Institute Catala dOncologia |
Gallardo D.,Institute Catala dOncologia |
Gonzalez-Campos J.,Hospital Universitario Virgen Del Rocio |
Hernandez-Rivas J.M.,University of Salamanca |
And 47 more authors.
Leukemia and Lymphoma
Acute lymphoblastic leukemia (ALL) following solid organ or hematologic malignancy (secondary ALL, s-ALL) is not well characterized. We analyzed the characteristics and outcome of patients with s-ALL and compared them with those of patients with de novo- ALL. Of 448 patients, 24 (5%) had previous neoplasia. Sixteen patients had received previous cytotoxic therapy (therapy-associated ALL, t-ALL), and eight had not (antecedent-malignancy ALL, am-ALL). Except for more advanced age in patients with s-ALL, no statistically significant differences were observed in WBC count, CNS involvement, immunophenotype or cytogenetics between the groups, nor in complete remission (t-ALL: 94%; am-ALL: 75%; de novo-ALL: 85%), 3-year remission duration (58%; 50%; 72%), overall survival (71%; 38%; 60%) or event-free survival (53%, 38%; 53%). Our study did not show poor clinical or cytogenetic features or inferior outcome in ALL patients with antecedent neoplastic disease, irrespective of the type of treatment received for the neoplasia. © 2015 Informa UK, Ltd. Source