High relapse rate of T cell acute lymphoblastic leukemia in adults treated with Hyper-CVAD chemotherapy in Sweden
ABSTRACT Hyper-CVAD is widely used to treat acute lymphoblastic leukemia (ALL) and aggressive lymphomas. This multicenter, population-based study assessed the efficacy of Hyper-CVAD as first line therapy in patients with T cell ALL (T-ALL).
Between October 2002 and September 2006, 24 patients were diagnosed with T-ALL in Sweden; 19 were eligible for treatment with the protocol.
The median age was 32 years (range 18-72 years). Complete remission (CR) was obtained in 17/19 (89%) patients, and the treatment was relatively well tolerated. Allogeneic stem cell transplantation (SCT) was recommended in high-risk disease and was performed in four patients upfront. Two and 5-year leukemia-free survivals (LFS) in 17 patients with CR achievement were identical, at 29% (95% confidence interval [CI]: 8-51). Two and 5-year overall survival (OS) in whole cohort were 63% (95% CI: 42-85) and 47% (95% CI: 26-69), respectively. The 5-year LFS for 15 patients who did not receive allogeneic SCT upfront was 20% (95%CI: 0-40), although 14/15 completed the protocol (eight cycles). Relapse occurred in 2/4 upfront-transplanted patients and in 12/15 patients treated with chemotherapy alone, six of whom received allogeneic SCT in CR2. Age ≥ 35 years influenced OS negatively in univariate analysis (HR 5.1, 95% CI: 1.55-16.7).
Hyper-CVAD treatment resulted in a high CR rate and appeared safe, but it showed poor efficacy at preventing relapse. Therefore, this treatment is no longer recommended for adults with T-ALL in Sweden. This article is protected by copyright. All rights reserved.
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ABSTRACT: To investigate the effectiveness of a combination of 6-thioguanine (6-TG) and pralatrexate (PDX) in methylthioadenosine phosphorylase (MTAP)-deficient T-cell acute lymphoblastic leukemia (T-cell ALL). CCRF-CEM (MTAP(-/-)) and Molt4 (MTAP(+/+)) T-cell ALL cell lines were treated with 6-TG or PDX and evaluated for efficacy 72 h later. NOD/SCID gamma mice bearing CEM or Molt4 xenografts were treated with 6-TG and PDX alone or in combination to evaluate antitumor effects. CEM cells were more sensitive to 6-TG and PDX in vitro than Molt4. In vivo, CEM cells were very sensitive to PDX and 6-TG, whereas Molt4 cells were highly resistant to 6-TG. A well-tolerated combination of PDX and 6-TG achieved significant tumor regression in CEM xenografts. The loss of MTAP expression may be therapeutically exploited in T-cell ALL. The combination of 6-TG and PDX, with the inclusion of leucovorin rescue, allows for a safe and effective regimen in MTAP-deficient T-cell ALL.Cancer Chemotherapy and Pharmacology 04/2015; 74(19 Supplement). DOI:10.1007/s00280-015-2747-2 · 2.57 Impact Factor