Favorable Outcome for Lymphoblastic Lymphoma (LL) After Frontline Therapy with the Hyper-CVAD Regimens: An Update.
Authors: Thomas Deborah A. , Faderl Stefan , O'Brien Susan , Wierda William G. , Ravandi Farhad , Garcia-Manero Guillermo , Verstovsek Srdan , Kornblau Steven M. , Fayad Luis , Cortes Jorge , Kantarjian Hagop M. 
Published: October 2019

Abstract
Abstract 4099
Outcome with LL has improved with the use of more intensive chemotherapy regimens designed for acute lymphoblastic leukemia (ALL). A prior report of 33 pts with de novo LL showed favorable outcomes with the hyper-CVAD regimens (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) [Thomas D, Blood 104:1624, 2004]. We updated their outcomes and reviewed the subsequent experience. From April 1992 to March 2009, 47 patients (pts) with newly diagnosed LL were treated with hyper-CVAD (n=20) or modified hyper-CVAD (n=11 with anthracycline intensification with liposomal daunorubicin-cytarabine for course 2, n=16 with subsequent regimen omitting anthracycline intensification). Intrathecal chemotherapy for CNS prophylaxis alternated methotrexate (MTX) and ara-C on days 2 and 7 of the first 4 courses. Mediastinal irradiation (XRT) was recommended for all pts presenting with bulky mediastinal disease (after consolidation prior to maintenance therapy). POMP (6-mercaptopurine, vincristine, MTX, prednisone) maintenance therapy was administered for 24 months with hyper-CVAD (intensifications with MTX-asparaginase months 7 & 11) with extension to 30 months with modified hyper-CVAD (intensifications with hyper-CVAD months 6 & 7 followed by MTX-asparaginase months 18 & 19). Allogeneic stem cell transplant (SCT) was considered in first remission only if inadequate response to therapy. Median age was 31 yrs (range, 17-59); 77% were males. Mediastinal disease was present in 74%, and 30% had pericardial and/or pleural effusions. Two pts had superior vena cava syndrome and five had CNS disease. T-cell immunophenotype was present in majority (79%). Eight (17%) pts had bone marrow involvement. Overall complete remission (CR) rate was 92% in 44 evaluable patients (3 in CR at start), with remainder achieving partial response (residual mediastinal disease not qualifying for CR). Of the 23 pts with mediastinal disease, 74% underwent XRT as planned. With a median follow-up of 73 months (range 23-187+ months), 31 (66%) pts remained alive without disease. Overall 3-yr rates for CR duration and survival were 72% and 74%, respectively. Fourteen pts relapsed or progressed within a median of 13 months (6 with standard, 8 with modified hyper-CVAD); five pts were successfully salvaged with chemotherapy and allogeneic SCT. Hyper-CVAD remains a highly active regimen for de novo LL. Anthracycline intensification did not improve the outcome. Nelarabine has now been incorporated into the modified hyper-CVAD regimen as a single agent for the consolidation (cycles 9 & 10) and maintenance (in lieu of early intensifications) phases given its activity in relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma; accrual is ongoing.

Disclosures:
No relevant conflicts of interest to declare.