Citations

Colony stimulating factor 3 receptor gene (CSF3R) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with CSF3R‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an ASXL1 and/or SETBP1 mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both SETBP1‐mutated and ASXL1‐unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both ASXL1‐mutated and SETBP1‐unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated ASXL1 (P = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (P = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of CSF3R‐mutated CNL and identifies mutant ASXL1 and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for SETBP1 and ASXL1 mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc.

BACKGROUNDPatients with polycythemia vera (PV) have historically been considered to be at high risk for perioperative hemorrhagic and thromboembolic complications. However, no recent studies have compared these outcomes between treated PV patients and patients without PV undergoing similar procedures.STUDY DESIGN AND METHODSPatients with PV who underwent surgery with anesthesia from June 1, 2006, to May 31, 2011, were randomly matched (sex, age, type of surgical procedure, surgical year) at a ratio of 1:4 with control patients without PV. Conditional logistic regression analysis adjusting for surgical duration, preoperative hemoglobin, platelet count, and cardiovascular disease was used to assess the association between PV and blood product transfusions, thromboembolism, and other major cardiovascular and pulmonary complications.RESULTSFifty‐six PV patients who underwent 79 surgeries were matched with 312 controls. During hospitalization, 35 (44.3%) and 82 (25.9%) PV and control patients, respectively, were transfused with blood products. PV patients were at increased risk for transfusion intraoperatively (odds ratio [OR], 4.35; 95% confidence interval [CI], 1.79‐10.57; p = 0.001) and during hospitalization (OR, 4.35; 95% CI, 1.84‐10.31; p < 0.001). The likelihood of thromboembolic complications and/or other major complications did not differ between the two study groups (thromboembolic—OR 1.53, 95% CI 0.39‐6.02, p = 0.540; other major complications—OR 2.15, 95% CI 0.93‐4.96, p = 0.073).CONCLUSIONSMedically managed PV patients had an increased likelihood of receiving blood products perioperatively. Given the low number of observed thromboembolic events, we cannot make definitive conclusions regarding the association between PV and thromboembolism.

Disease overview: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs.Diagnosis: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V.Risk stratification: The 2008 World Health Organization classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent SM (ISM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD), and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis.Management: SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (+/−corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KITD816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting; there is a role for allogeneic stem cell transplantation in select cases.Investigational Drugs: Recent data confirms midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 90:251–262, 2015. © 2015 Wiley Periodicals, Inc.

Most studies in polycythemia vera (PV) include patients with both remote and most recent diagnostic periods and are therefore vulnerable to inaccurate interpretation of time‐dependent data. We addressed the particular issue by analyzing presenting characteristics and outcome data among 1,545 patients with WHO‐defined PV stratified by a diagnosis period of before or after 2005, which coincides with the first description of JAK2V617F as the molecular marker of PV. Patients diagnosed after 2005 displayed lower hemoglobin values (P < 0.0001) and older age (P = 0.007) at diagnosis; we suggest ease of diagnosis offered by a molecular marker enabled earlier diagnosis and broader application across older age groups that is further enhanced by recent trends in increased attention and health monitoring for the elderly. Post‐2005 diagnosed patients were also more or less likely to receive aspirin and cytoreductive therapy, respectively, and, despite their older age distribution, displayed significantly lower risk of thrombosis in high risk disease. Regardless of the contributing factors to the latter phenomenon, our observations underscore the need to reassess current demographics and frequencies of thrombosis in clinical trial designs including thrombosis prevention in PV. Am. J. Hematol. 90:434–437, 2015. © 2015 Wiley Periodicals, Inc.

SummaryAmong 826 patients with primary myelofibrosis (PMF) and analysable metaphases on cytogenetic studies, 352 (42·6%) had abnormal karyotype, of which 240 (68·2%) were sole aberrations and 48 (13·6%) were complex; the most frequent abnormalities were 20q− (23·3%), 13q− (18·2%), +8 (11·1%), +9 (9·9%), chromosome 1q+ (9·7%) and −7/7q− (7·1%). Phenotypic correlates included: abnormal karyotype with anaemia (P = 0·02), leucopenia (P < 0·01) and thrombocytopenia (P < 0·01); complex karyotype with younger age (P = 0·04) and thrombocytopenia (P < 0·01); leucopenia with 20q−, +8 and −7/7q− and thrombocytopenia with 20q− and −7/7q−. Cytopenias were less likely to occur with 13q−. 476 patients were annotated for JAK2/CALR/MPL mutations; abnormal karyotype frequencies were 43% in JAK2, 42% CALR, 33% MPL mutated and 34% triple‐negative cases (P = 0·3). A proportion of patients were also screened for ASXL1, EZH2, IDH1, IDH2, SRSF2, U2AF1 and SF3B1 mutations; in all instances, mutational frequencies were higher in patients with normal karyotype, reaching significance for ASXL1 (P = 0·02) and U2AF1 (P = 0·01). 13q− was associated with mutant CALR (P = 0·03), +9 with mutant JAK2 (P = 0·02) and 20q− with mutant SRSF2 (P = 0·02). The current PMF study provides detailed cytogenetic information and correlations with mutations and clinical phenotype.

SummaryMomelotinib (a JAK1 and JAK2 inhibitor) induces both anaemia and spleen responses in myelofibrosis (MF). Momelotinib treatment‐emergent peripheral neuropathy (TE‐PN) was documented in 44 (44%) of 100 MF patients treated at our institution; median time of TE‐PN onset was 32 weeks and duration 11 months. Improvement after drug dose reduction or discontinuation was documented in only two patients. TE‐PN was significantly associated with treatment response (P = 0·02) and longer survival (P = 0·048) but significance was lost during multivariate analysis that included treatment duration. TE‐PN did not correlate with initial or maximum momelotinib dose or previous treatment with JAK inhibitor or thalidomide.