Long-term Follow-up Results of Adult Patients with Acute Lymphocytic Leukemia or Lymphoblastic Lymphoma Treated with Short-term, Alternating Non-cross-resistant Chemotherapy: Japan Clinical Oncology Group Study 8702

Abstract

Background: Patients with acute lymphocytic leukemia (ALL) and those with lymphoblastic lymphoma (LBL) have overlapping clinical and immunophenotypic features and they have been treated with the same or very similar chemotherapy regimens. The goal of this multi-institutional phase II trial was to evaluate the therapeutic efficacy of a short-term, six-drug chemotherapy regimen for adult patients with untreated ALL or LBL.Methods: Forty-six eligible patients, 41 with ALL and five with LBL, were treated with a short-term (planned total therapy duration; 36-38 weeks), simplified chemotherapy program; two courses of VEPA-L (vincristine, cyclophosphamide, prednisolone, doxorubicin, I-asparaginase plus intrathecal methotrexate and prednisolone) followed by four courses of M-VEPA (methotrexate plus VEPA), without the traditional maintenance therapy using daily 6-mercaptopurine and weekly methotrexate. Results: Thirty-six (78%; 95% confidence interval 64-89%) of the 46 eligible patients achieved complete remission (CR). Among the 36 patients who achieved CR, four (11 %) died of treatment complications, 26 (72%) relapsed and six (17%) remain alive in continuous CR. The median survival for all 46 eligible patients is 14 months and the median disease-free survival (DFS) for the 36 patients who achieved CR is 11 months. The estimate of the proportion of survival at 7 years of all 46 eligible patients is 15% at a median follow-up time of 96 months and that of DFS of the 36 patients achieving CR is 17% at a median follow-up time of 93 months. Subgroup analysis showed that an elevated serum C-reactive protein (CRP) level, age of 30 years or older, the presence of B-symptom and T-cell phenotype were likely to be associated with shortened survival. Although the observed CR rate (78%) is within the range of satisfaction, the long-term survival rate (15%) is inferior to those of published programs incorporating maintenance therapy.Conclusions: A fraction of adult patients with ALL or LBL are curable with a short-term, six-drug chemotherapy regimen. However,this simplifiedtherapy of shorter duration cannot be recommended.

Intravascular large B cell lymphoma: proposed of the strategy for early diagnosis and treatment of patients with rapid deteriorating condition

“…Most of the patients received systemic chemotherapy. IVL cases treated before the R-era (cases 1-8) were treated using multiagent chemotherapy regimens, such as CHOP, THP-COP [41,42], VEPA-L [43] or CAMBO-VIP [44]. Only three of these eight patients achieved complete remission, and all except one patient (case 3 with a long survival period) showed poor prognosis with survival duration from diagnosis ranging from 14 days to 17 months.…”

Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor α-chain predicts a poor prognosis

“…One hundred and eighty-five patients were treated with Japanese ALL protocols including a combination of intravenous anthracycline (doxorubicin (DXR), mitoxantrone (MIT) or daunorubicin (DNR)), vincristine (VCR), cyclophosphamide (CY) and lasparaginase (Asp) and oral prednisolone (PSL), together with intrathecal methotrexate (MTX), cytarabine (Ara-C) and PSL: JCOG8702 14 (29); 60-40 mg/m 2 PSL for 10-28 days; 600-1200 mg/m 2 CY for 1-3 days intermittently; 3000-6000 IU/m 2 Asp for 2-10 days. For patients who achieved a complete remission (CR), consolidation, intensification and maintenance chemotherapies were carried out as a post-remission therapy with additional drugs such as MTX, Ara-C, etoposide, behnoyl-ara-C, vindesine, DNR, aclarubicin and 6-mercaptopurine.…”

Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma

“…More intensive chemotherapy regimens appear to be superior to less intensive regimens, shorter-term chemotherapy regimens without maintenance therapy appear to increase the risk of relapse, and intensive CNS prophylaxis is required to reduce the incidence of CNS relapse. 1,[17][18][19] This report summarizes the experience with hyper-CVAD 20 (fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and modified hyper-CVAD 21 dose-intensive regimens used for adult ALL at our institution, in patients with LL.…”