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

Temozolomide-induced aplastic anaemia: Case report and review of the literature

Temozolomide (TMZ) is an oral alkylating agent principally indicated for neurological malignancies including glioblastoma (GBM) and astrocytoma. Most common side effects are mild to moderate, and include fatigue, nausea, vomiting, thrombocytopenia and neutropenia. Severe or prolonged myelosuppression, causing delayed treatment or discontinuation, is uncommon. Major haematological adverse effects such as myelodysplastic syndrome or aplastic anaemia (AA) have rarely been reported.We report a 68-year old female with GBM treated at a tertiary hospital with short-course radiotherapy and concurrent temozolomide following craniotomy. On treatment completion she was transferred to our hospital for rehabilitation. She was thrombocytopenic on admission. Platelets continued falling with significant pancytopenia developing over the next two weeks. Blood parameters and a markedly hypocellular bone marrow confirmed the diagnosis of very severe AA, probably due to TMZ.Treatment consisted of repeated platelet transfusions, intravenous antibiotics, antiviral and antifungal prophylaxis, and G-CSF 300 mcg daily. Platelet and neutrophil counts had returned to normal at 38 days following the completion of TMZ treatment.Whilst most cases of AA are idiopathic, a careful drug, occupational exposure and family history should be obtained, as acquired AA may result from viruses, chemical exposure, radiation and medications. Temozolomide-induced AA is well documented, though only 12 cases have been described in detail. Other potential causes were eliminated in our patient. Physicians should be aware of this rare and potentially fatal toxicity when prescribing. Frequent blood tests should be performed, during and following TMZ treatment, to enable early detection