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The article presents a study on leukemic cell priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) which may modulate cell cycle kinetics and susceptible to phase-specific chemotherapeutic agents. In this study, cytogenetics, mutation detection and statistical analysis were used to 259 patients with acute myeloid leukemia (AML). The results show that priming of leukemia cells with GM-CSF may enhance complete remission (CR) rate and event-free survival (EFS).

Several reports of successful empirical treatment of idiopathic hypereosinophilic syndrome with imatinib led to the recent identification of the FIP1L1–PDGFRA fusion gene rearrangement, which characterizes a distinctive group of chronic eosinophilic leukemias. This fusion gene can be detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes in FIP1L1–PDGFRA-positive hypereosinophilic patients suggesting a multilineage involvement. Furthermore, the same FIP1L1–PDGFRA rearrangement was identified in patients with hypereosinophilia and atypical mast cell proliferations, raising the question of a disease with two concomitant lines of differentiation. In addition, a recent report noted two cases with the association of FIP1L1–PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma (T-LBL). We report here the only third case of synchronous chronic eosinophilic leukemia and T-LBL, both associated with a FIP1L1–PDGFRA fusion transcript, confirming the occurrence of such disease and suggesting a clonal proliferation with two lines of differentiation probably arising from a primitive multipotent medullary stem cell. [ABSTRACT FROM AUTHOR]

In spite of the recent improvement in the outcome of acute promyelocytic leukaemia (APL) with treatment combining all trans retinoic acid (ATRA) and chemotherapy (CT), some patients with this disease still have a poor outcome. The prognostic significance of chromosomal abnormalities in addition to t(15;17) in APL is uncertain. We examined the prognostic significance of secondary chromosomal changes in 292 patients included in a European trial who were treated with ATRA and CT. The incidence of chromosomal abnormalities in addition to t(15;17) was 26% and trisomy 8 was the most frequent secondary change (46% of the cases with secondary changes). No significant differences were seen with regard to age, sex, initial white blood cell count, % of circulating blasts, platelet count, fibrinogen level and incidence of microgranular variants between patients with or without additional rearrangements. Outcome was also similar between patients with t(15;17) alone and patients with t(15;17) and other clonal abnormalities for complete remission (92% vs. 93% respectively), event-free survival at 2 years (76·1% vs. 78·1% respectively), relapse at 2 years (16·7% vs. 11·6% respectively) and overall survival at 2 years (79·9% vs. 79·5% respectively). Analysis according to the type of induction treatment (ATRA followed by CT or ATRA plus CT) or the type of maintenance treatment (with ATRA, low-dose CT or both) also failed to show any difference between the two groups. Thus, in a large cohort of APL patients treated with ATRA and CT, additional chromosomal abnormalities had no impact on prognosis. [ABSTRACT FROM AUTHOR]

The article presents information on a study which showed that the outcome of high risk myelodysplastic syndrome (MDS) after azacitidine (AZA) failure. The study the outcome of 74 patients with secondary acute myeloid leukaemia (AML) after AZA treatment failure, collected from two Johns Hopkins University trials and the French AZA compassionate programme.

The article reports that activating somatic mutations in Tyrosine Kinase (TK) genes are frequent events in haematological malignancies. The structural and functional consequences of these mutations were variable in molecular modelling. Group for Research on Adult Acute Lymphoblastic Leukaemia (GRAAL) study included assesment of JAK1, a Janus Kinase (JAK) family member.

Limited data are available on azacitidine (AZA) treatment and its prognostic factors in acute myeloid leukemia (AML). One hundred and forty-nine previously untreated AML patients considered ineligible for intensive chemotherapy received AZA in a compassionate patient-named program. AML diagnosis was de novo, post-myelodysplastic syndromes (MDS), post-MPN, and therapy-related AML in 51, 55, 13, and 30 patients, respectively. Median age was 74 years, median white blood cell count (WBC) was 3.2 × 10⁹ /L and 58% of the patients had ≥ 30% marrow blasts. Cytogenetics was adverse in 60 patients. Patients received AZA for a median of five cycles (range 1-31). Response rate (including complete remission/CR with incomplete recovery/partial remission) was 27.5% after a median of three cycles (initial response), and 33% at any time (best response). Only adverse cytogenetics predicted poorer response. Median overall survival (OS) was 9.4 months. Two-year OS was 51% in responders and 10% in non-responders (P<0.0001). Adverse cytogenetics, WBC >15 × 10⁹ /L and ECOG-PS ≥ 2 predicted poorer OS, while age and marrow blast percentage had no impact. Using MDS IWG 2006 response criteria, among patients with stable disease, those with hematological improvement had no significant survival benefit in a 7 months landmark analysis. Outcomes observed in this high-risk AML population treated with AZA deserve comparison with those of patients treated intensively in prospective studies., (Copyright © 2013 Wiley Periodicals, Inc.)