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Background: Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME).Methods: Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS).Results: Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS.Conclusions: SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML. [ABSTRACT FROM AUTHOR]

Objective: To define the clinicopathologic features, outcome, and prognostic indicators of myelofibrosis (MF) in Asian patients. Methods: Two hundred and seventy consecutive Chinese patients (primary MF, n = 207; post-polycythemia vera MF, n = 27; and post-essential thrombocythemia MF, n = 36) from seven regional referral hospitals were analyzed. Results: The median overall survival (OS) for primary MF was 66 months. Multivariate analysis showed that age >65 years (P = 0.02), platelet count <100 × 109/l (P = 0.001), and leukemic transformation (P = 0.001) negatively impacted on OS. The median OS of 63 patients with secondary MF was 44 months. In primary MF, the 10-year cumulative risk of leukemic transformation was 28%. On multivariate analysis, unfavorable karyotypes significantly predicted inferior leukemia-free survival (LFS) (P = 0.03). In secondary MF, the 10-year cumulative risk of leukemic transformation was 31%. Circulating blasts ≥1% significantly predicted inferior LFS (P = 0.04). The international prognostic scoring system (IPSS) and dynamic IPSS were not significant survival predictors in our cohort. Eighteen patients underwent allogeneic hematopoietic stem cell transplantation. The median OS post-transplantation was merely 19 months. Discussion: Platelet count <100 × 109/l, unfavorable karyotypes, and circulating blasts >1% were negative prognostic indicators. Conclusion: Chinese MF patients were similar to Western patients in clinicopathologic features and outcome. [ABSTRACT FROM AUTHOR]

Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As2O3)-based maintenance. Three regimens were used: oral As2O3 (10 mg/day, regimen A, n = 20), oral As2O3 plus all-trans retinoic acid (ATRA, 45 mg/m² per day, regimen AA, n = 19), and oral As2O3 plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As2O3 maintenance regimens had no impact on survivals. Prolonged oral As2O3 maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Cryoglobulins are immunoglobulins that precipitate in the serum upon cooling to below core body temperature and re-dissolve at higher temperatures. Cryoglobulinaemia may be life-threatening. The three types of cryoglobulinaemia are associated with a wide spectrum of haematological, autoimmune, and chronic infectious diseases, especially hepatitis C infection. Our laboratory has received 378 requests for cryoglobulin testing over the past 5 years, with a detection rate of 4.8% in the 271 patients involved. Twelve per cent of the specimens were not processed due to being at an inappropriate temperature on arrival at the laboratory. Clinicians should be aware of temperature requirements when requesting cryoglobulin testing in suspected cases, and for all relevant protein tests in patients with cryoglobulinaemia. Handling specimens at inappropriate temperatures in the pre-analytical and analytical phases of the investigation might lead to cryoprecipitation and therefore false-negative results. The potential pitfalls encountered with specimen handling, analysis, and result interpretation are discussed in detail.

A 42-year-old male with stage IV mantle cell lymphoma received chemotherapy and autologous peripheral blood stem cell transplantation. He developed pancytopaenia, and bone marrow examination indicated a parvovirus B19 (PVB 19)-induced red cell aplasia, confirmed by virological tests. Multiple doses of intravenous immunoglobulin (IVIG) were given over the following months, with blood samples being taken after each dose for quantitative PVB 19 DNA and hematological testing to assess the response. Each dose of IVIG produced a 1-3 log(10) drop in PVB 19 DNA levels. Eventually, after the fifth dose of IVIG, the PVB 19 DNA was reduced to <10 copies/ml serum, with a gradual improvement in his hematological parameters. This report demonstrates how close monitoring of the virological and hematological response to IVIG therapy for persistent PVB 19 infection in an immunocompromised patient can optimize the usage of this relatively expensive, and sometimes scarce intervention.