Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

A patient with a diagnosis of nodal marginal zone B-cell lymphoma and a t(2;14)(p24;q32) involving MYCN and IGH

Abstract Background Nodal marginal zone B-cell lymphoma is a rare entity in which the cytogenetic findings are not well defined. The t(2;14)(p24;q32) has previously been reported in three patients with blastic mantle cell lymphoma and one patient with follicular lymphoma. This rearrangement has not been reported previously in a patient with a diagnosis of nodal marginal zone B-cell lymphoma. Case presentation We present a male patient who presented with lymphadenopathy. On the basis of his clinicoradiologic presentation, morphological appearances, immunophenotype and molecular findings he was determined to have a diagnosis of nodal marginal zone B-cell lymphoma. Cytogenetic analysis demonstrated a t(2;14)(p24;q32). Further FISH testing showed this rearrangement to involve the MYCN and IGH genes. Conclusions We present the first patient with a diagnosis of nodal marginal zone B-cell lymphoma with a t(2;14)(p24;q32). This rearrangement has been described in three other patients who have had a diagnosis of lymphoma. Our findings suggest this rearrangement is not specific to mantle cell lymphoma or follicular lymphoma. The number of cases described are still too low to draw firm conclusions regarding the nature of this rearrangement. In order to refine the clinical and prognostic picture of this finding, publication of further cases is required