Cerebral vein thrombosis in patients with Philadelphia‐negative myeloproliferative neoplasms An European Leukemia Net study

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN‐CVT) to 87 with MPN and other venous thrombosis (group MPN‐VT) and 178 with MPN and no thrombosis (group MPN‐NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN‐CVT and MPN‐VT than in MPN‐NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN‐VT, MPN‐CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow‐up period (6.1 vs. 10.3 years, P = 0.019), a higher long‐term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN‐CVT than in MPN‐VT group (8.8% and 4.2% patient‐years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05–3.72 and 2.09, 1.09–4.00, respectively). Am. J. Hematol. 89:E200–E205, 2014. © 2014 Wiley Periodicals, Inc.     

Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan

Eighty-three patients with various chronic myeloproliferative disorders [polycythemia vera (PV), essential thrombocytosis (ET), idiopathic myelofibrosis (IMF)] were analyzed for the occurrence of acute myeloid leukemia (AML) and myelodysplasia (MDS) during treatment with hydroxyurea (HU) alone or HU following treatment with busulphan (BU). A total of 58 patients (29 PV, 14 ET, 12 IMF, 3 unclassified) had been treated with HU. Thirty-five of these patients had been treated with HU alone whereas 18 patients had received both HU and BU. The follow-up period was 7.8 years. Twenty-five patients had not been treated with HU. In this patient group, 4 patients had been treated with BU. The follow-up period was 10.5 years. In the HU-treated group (n = 58) 7 patients developed AML and 5 patients MDS. Five of the 12 patients had been treated with HU alone, and 4 patients had received both HU and BU. In the non-HU-treated group (n = 25) 1 patient with PV developed acute myeloid leukemia (AML). This patient had only been treated with phlebotomies. It is concluded that treatment with HU is leukemogenic, with an incidence of AML and MDS of approximately 14% when used alone. The incidence is markedly increased to about 30% when HU is preceded by treatment with BU. HU is not recommended for use in younger patients, in whom non-leukemogenic agents such as alpha-interferon and anagrelide should be used instead.     

Postallogeneic monitoring with molecular markers detected by pretransplant next‐generation or Sanger sequencing predicts clinical relapse in patients with myelodysplastic/myeloproliferative neoplasms

Relapse is the major cause of treatment failure after allogeneic stem‐cell transplantation (AHSCT) for patients with myelodysplastic syndrome/myeloproliferative syndrome neoplasms (MDS/MPN). We evaluated the impact of molecular mutations on outcome and the value of molecular monitoring post‐transplantation. We screened 45 patients with chronic myelomonocytic leukemia (n = 39 patients, including seven with transformed‐acute myeloid leukemia), MDS/MPN unclassifiable (n = 5), and atypical BCR‐ABL1‐negative CML (n = 1) for mutations in ASXL1, CBL, NRAS, and TET2 genes by molecular genetics including a sensitive next‐generation sequencing (NGS) technique. In 36 patients, sufficient DNA was available for molecular analyses. In particular, TET2 and CBL mutations were screened applying amplicon deep sequencing. In 89% of cases, at least one mutation could be detected: ASXL1: n = 18 (50%); CBL: n = 7 (19%); TET2: n = 15 (42%); and NRAS: n = 11 (32%). Survival after AHSCT at 5 yr was 46% (95% CI 28–64%) and was not influenced by any mutation. After a median of 6 months after AHSCT in 33% of the patients, one of the molecular markers was still detectable, resulting in a higher incidence of relapse than in patients with undetectable mutations (50% vs. 15%, P = 0.04). In conclusion, pretransplant molecular mutation analysis can help to detect biomarkers in patients with MPN/MDS, which may be subsequently used as minimal residual disease markers after AHSCT.     

Substantial variation in post‐engraftment infection prophylaxis and revaccination practice in autologous stem cell transplant patients

There is a paucity of evidence supporting the necessity or duration of Pneumocystis jirovecii and antiviral prophylaxis as well as revaccination following autologous stem cell transplant (ASCT). A survey aimed at evaluating these policies was distributed to 34 ASCT centres across Australasia. The 26 survey respondents demonstrated significant heterogeneity in their infection prophylaxis and revaccination strategy post‐transplant despite the availability of consensual guidelines.     

Lamivudine prophylaxis is effective in reducing hepatitis B reactivation and reactivation‐related mortality in chemotherapy patients: a meta‐analysis

Background: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation‐related liver disease survival is unclear. Objective: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation‐related survival in patients with HBV undergoing chemotherapy. Methods: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman . Results: Eleven studies met the defined inclusion criteria and were included in the analysis. Two‐hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07–0.24] than patients not given prophylaxis [absolute risk reduction (ARR) ?0.46, 95% CI, ?0.61 to ?0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation‐related mortality (RR 0.30, 95% CI, 0.1–0.94) compared with controls (ARR ?0.03, 95% CI, 0.07–0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27–0.63; ARR ?0.33, 95% CI, ?0.33 to ?0.15). There was no significant heterogeneity in the comparisons. Conclusion: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation‐related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.     

Physical activity for prevention of osteoporosis in patients with severe haemophilia on long‐term prophylaxis

Summary. Physical activity has been considered as an important factor for bone density and as a factor facilitating prevention of osteoporosis. Bone density has been reported to be reduced in haemophilia. To examine the relation between different aspects of physical activity and bone mineral density (BMD) in patients with severe haemophilia on long‐term prophylaxis. The study group consisted of 38 patients with severe haemophilia (mean age 30.5 years). All patients received long‐term prophylaxis to prevent bleeding. The bone density (BMD g cm⁻²) of the total body, lumbar spine, total hip, femoral neck and trochanter was measured by dual energy X‐ray absorptiometry. Physical activity was assessed using the self‐report Modifiable Activity Questionnaire, an instrument which collects information about leisure and occupational activities for the prior 12 months. There was only significant correlation between duration and intensity of vigorous physical activity and bone density at lumber spine L1‐L4; for duration (r = 0.429 and P = 0.020) and for intensity (r = 0.430 and P = 0.019); whereas no significant correlation between all aspects of physical activity and bone density at any other measured sites. With adequate long‐term prophylaxis, adult patients with haemophilia are maintaining bone mass, whereas the level of physical activity in terms of intensity and duration play a minor role. These results may support the proposition that the responsiveness to mechanical strain is probably more important for bone mass development in children and during adolescence than in adults and underscores the importance of early onset prophylaxis.