Shorter Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia: The Experience of the Prospective, Randomized Brazilian GBTLI ALL-93 Protocol

Maintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate (MTX) with daily 6-mercaptopurine (6MP) constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in Limited-Income countries (LIC). Objective: To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs 24 months duration. Materials and Methods: From October 1993 to September 1999, 867 consecutive untreated ALL patients 10 years and high WBC at diagnosis). Overall death in remission rate was 6.85% (56 patients). Deaths during maintenance were 13 in group 1 and 12 in group 2, all due to infection. Over 15 years of follow-up, two patients both from Group 2 presented a second malignancy (Hodgkin’s disease and thyroid carcinoma) after 8.3 and 11 years off therapy, respectively. Conclusion: Six-month reduction of maintenance therapy in ALL children treated according to the GBTLI ALL-93 protocol, provided the same overall outcome as 2-year duration regimen

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

Background: Small, randomized trials of cervical artery dissection (CAD) patients showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with CAD treated with antiplatelets versus anticoagulation. Methods: This is a multi-center observational retrospective international study (16 countries, 63 sites) that included CAD patients without major trauma. The exposure was antithrombotic treatment type (anticoagulation vs. antiplatelets) and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with Inverse Probability of Treatment Weighting (IPTW) to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an "as treated" cross-over approach and only included outcomes occurring on the above treatments. Results: The study included 3,636 patients [402 (11.1%) received exclusively anticoagulation and 2,453 (67.5%) received exclusively antiplatelets]. By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with IPTW, compared to antiplatelet therapy, anticoagulation was associated with a non-significantly lower risk of subsequent ischemic stroke by day 30 (adjusted HR 0.71 95% CI 0.45-1.12, p=0.145) and by day 180 (adjusted HR 0.80 95% CI 0.28-2.24, p=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR 1.39 95% CI 0.35-5.45, p=0.637) but was by day 180 (adjusted HR 5.56 95% CI 1.53-20.13, p=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR 0.40 95% CI 0.18-0.88) (Pinteraction=0.009). Conclusions: Our study does not rule out a benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings