Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

Abstract

Purpose This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). Patients and Methods This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. Results The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. Conclusion In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.

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

“…From that point of view, it is very interesting to observe that the same T-cell genetic classification has recently been demonstrated as a strong outcome predictor in children and adults with T-cell lymphoblastic lymphoma, a thymic disease in which BM MRD evaluation is obviously of lower interest. 50,51 For all these reasons, in the next GRAALL-2014 trial, we will base the decision of SCT in CR1 on early MRD response only.…”

Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype

“…This is consistent with other published series. 22,23 ETP-ALL/LBL represents a disease subtype whereby blasts are derived from the earliest T-cell precursors in the thymus and have multilineage pluripotency. 5,7,8 In children, ETP-ALL/LBL is associated with older age and a lower presenting WBC count than seen in the non-ETP-ALL/LBL patients.…”

Terminal deoxynucleotidyl transferase (TdT)-negative T-cell lymphoblastic lymphoma with loss of the T-cell lineage-specific marker CD3 at relapse: a rare entity with an aggressive outcome

“…Using ALL-type regimen improvements were noted in long-term outcomes both in children and adults 16. After the success of paediatric-inspired ALL regimens in ALL, GRAALL-LYSA LL03 study first evaluated its efficacy in 148 untreated patients of LBL (131 T-LBL, 17 B-LBL) and found good response rate and outcome 17. The 3-year event-free survival, disease-free survival and overall survival were 63.3%, 72.4% and 69.2%, respectively, in these patients 17.…”

“…After the success of paediatric-inspired ALL regimens in ALL, GRAALL-LYSA LL03 study first evaluated its efficacy in 148 untreated patients of LBL (131 T-LBL, 17 B-LBL) and found good response rate and outcome 17. The 3-year event-free survival, disease-free survival and overall survival were 63.3%, 72.4% and 69.2%, respectively, in these patients 17. Central nervous system (CNS) prophylaxis with high-dose systemic chemotherapy and intrathecal chemotherapy is also suggested as the CNS relapse rate range from 42% to 100% when no prophylaxis is done 16.…”