Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m2 intravenously on day 1), all-trans retinoic acid (45 mg/m2 orally on days 4–6 and 15 mg/m2 orally on days 7–28), high-dose cytarabine (3 g/m2/12 h intravenously on days 1–3) and mitoxantrone (12 mg/m2 intravenously on days 2–3) in 93 patients aged 18–60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died. Allogeneic hematopoietic cell transplantation was performed in 71 (76%) patients; 6 of the 71 (8.5%) patients developed moderate or severe sinusoidal obstruction syndrome after transplantation. Four-year overall survival rate was 32% (95% confidence interval 24%-43%). Patients responding to salvage therapy and undergoing allogeneic hematopoietic cell transplantation (n=51) had a 4-year survival rate of 49% (95% confidence intervaI 37%-64%). Patients with fms-like tyrosine kinase internal tandem duplication positive acute myeloid leukemia had a poor outcome despite transplantation. In conclusion, the described regimen is an effective and tolerable salvage therapy for patients who are primary refractory to one cycle of conventional intensive induction therapy. (clinicaltrials.gov identifier: 00143975

Deregulated Expression of EVI1 Defines a Poor Prognostic Subset of MLL-Rearranged Acute Myeloid Leukemias:A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group

<p>Purpose</p><p>To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements.</p><p>Patients and Methods</p><p>We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis.</p><p>Results</p><p>We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1(+)) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1(+) was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1(+) AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v0%; Mantel-Byar, P = .0006). EVI1(-) t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P <.001). Among t(9;11) AMLs, EVI1(+) again was the sole independent adverse prognostic factor for survival.</p><p>Conclusion</p><p>Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1(+) MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR. J Clin Oncol 31:95-103. (c) 2012 by American Society of Clinical Oncology</p>