PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase.

Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened (SMO) expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML) patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP) using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis.

Risk of thrombosis according to need of phlebotomies in patients with polycythemia vera treated with hydroxyurea.

Hematocrit control below 45% is associated with a lower rate of thrombosis in polycythemia vera. In patients receiving hydroxyurea, this target can be achieved with hydroxyurea alone or with the combination of hydroxyurea plus phlebotomies. However, the clinical implications of phlebotomy requirement under hydroxyurea therapy are unknown.

Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation.

The role of antiplatelet therapy as primary prophylaxis of thrombosis in low-risk essential thrombocythemia has not been studied in randomized clinical trials. We assessed the benefit/risk of low-dose aspirin in 433 patients with low-risk essential thrombocythemia (271 with a CALR mutation, 162 with a JAK2(V617F) mutation) who were on antiplatelet therapy or observation only. After a follow up of 2215 person-years free from cytoreduction, 25 thrombotic and 17 bleeding episodes were recorded.

Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythaemia vera.

The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra-haematological toxicity (9%). With a median follow-up of 4·6 years, 99 patients died, resulting in a median survival of 19 years.

Adult-onset Diamond-Blackfan anemia with a novel mutation in the exon 5 of RPL11: too late and too rare.

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia usually diagnosed in the early infancy and associated with mutations or large deletions in 11 ribosomal protein (RP) genes. Adult patients with severe, transfusion dependence, aregenerative anemia might have a genetic-in-origin disease with an atypical presentation. Late onset nonclassical DBA should be ruled out and mutations of RP genes studied.

A team-based multidisciplinary approach to managing peripherally inserted central catheter complications in high-risk haematological patients: a prospective study.

Purpose: Use of peripherally inserted central catheters (PICCs) has markedly increased during the last decade. However, there are few studies on use of PICCs in patients with haematological malignancies (HM) receiving intensive chemotherapy. Preliminary data suggest a higher rate of PICC-related complications in these high-risk patients.

Switching to second-generation tyrosine kinase inhibitor improves the response and outcome of frontline imatinib-treated patients with chronic myeloid leukemia with more than 10% of BCR-ABL/ABL ratio at 3 months.

Chronic myeloid leukemia patients display heterogeneous responses to imatinib. Survival depends on baseline clinical characteristics (including prognostic scoring systems) and on early response (such as >10% BCR-ABL/ABL ratio at 3 months of therapy). The results of switching to second-generation tyrosine kinase inhibitors (2GTKIs) may contain a bias since, in the majority of these studies, patients who switch treatment due to intolerance or failure are censored or excluded.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]).

Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea.

Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n = 15, ET n = 21) treated for a median of 256 days.

Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry: a bridge to individualized medicine.

Background: We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models.

Patients And Methods: Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells.

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm.

This study aimed to assess the antitumour effects, molecular mechanisms of action, and potential synergy of ruxolitinib with sorafenib, KNK437, dasatinib, and perifosine, in Philadelphia-negative chronic myeloproliferative neoplasms (MPN). Cytotoxic and cytostatic effects of the different compounds were determined in the JAK2 V617F-positive cell lines, HEL and Ba/F3 (JAK2V617F EPOR) , and in primary mononuclear and bone marrow CD34-positive cells from 19 MPN patients. Ruxolitinib [50% inhibitory concentration (IC50 )(PV)  = 15 nmol/l], as well as sorafenib (IC50 PV=8μmol/l), KNK437 (IC50 PV=100μmol/l ), and perifosine (IC50 PV=15μmol/l ), were able to inhibit proliferation in cell line models and in primary cells from MPN patients.

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma.

The activity and safety of two-weekly dose-adjusted (DA)-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin)-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) was explored in 20 patients with previously untreated poor prognosis diffuse large B-cell lymphoma (DLBCL). The main outcomes were compared with those of 27 poor-prognosis patients enrolled into a previous trial of 3-weekly DA-EPOCH-R. Toxicity was manageable and there were no therapy-related deaths.

Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera.

Criteria of response and definition of resistance and intolerance to hydroxyurea (HU) in polycythemia vera (PV) were proposed by the European LeukemiaNet (ELN). Such criteria were evaluated in 261 PV patients (median follow-up, 7.2 years) treated with HU for a median of 4.

Frontline treatment of follicular lymphoma with fludarabine, cyclophosphamide, and rituximab followed by rituximab maintenance: toxicities overcome its high antilymphoma effect. Results from a Spanish Cooperative Trial (LNHF-03).

We assessed the efficacy of fludarabine, cyclophosphamide, and rituximab in combination (FCR) as frontline treatment in patients with follicular lymphoma (FL) followed by rituximab maintenance. Seventy-five untreated patients with FL received FCR followed by maintenance with rituximab 375 mg/m(2) weekly during 4 weeks and every 6 months for 2 years. The overall response rate was 100%, with 89% complete remission (CR) and 11% partial remission (PR).

Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia.

The effectiveness of antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia (ET) is not proven. In this study, the incidence rates of arterial and venous thrombosis were retrospectively analyzed in 300 low-risk patients with ET treated with antiplatelet drugs as monotherapy (n = 198) or followed with careful observation (n = 102). Follow-up was 802 and 848 person-years for antiplatelet therapy and observation, respectively.

Influence of MBL-2 mutations in the infection risk of patients with follicular lymphoma treated with rituximab, fludarabine, and cyclophosphamide.

The employment of current treatments based on chemotherapy and immunotherapy leads to inmunosuppression. The presence of mutations or polymorphisms in genes related to immune system might involve an additional disadvantage. The aim of the present study was to analyze mannose-binding lectin (MBL-2 gene) mutations and their association with severe infections and event-free survival in patients diagnosed with follicular lymphoma, treated uniformly, in the clinical trial LNHF-03.

[Retrospective analysis of the efficacy and tolerability of anagrelide in patients with essential thrombocytemia: Spanish registry of essential thrombocytemia].

Background And Objective: A retrospective analysis of a registration database was used to assess the efficacy and tolerability of anagrelide for treating essential thrombocythemia (ET). The study was conducted by analysing information on response to treatment, time to response and tolerability.

Patients And Method: A total of 411 patients with ET from 54 centres in Spain were included in a retrospective chart review.

Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study.

This study was designed to assess the efficacy and safety of an infusional DA-EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA-EPOCH-R) regimen for patients with poor prognosis diffuse large B-cell lymphoma (DLBCL). Thirty-three patients, aged 21-76 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (> or =10 cm) disease at presentation.

Changes in the natural history of progressive multifocal leukoencephalopathy in HIV-negative lymphoproliferative disorders: impact of novel therapies.

The aims of this study were to evaluate the clinical characteristics of HIV-negative patients affected by lymphoproliferative disorders (LPD) who developed progressive multifocal leukoencephalopathy (PML), to delineate the risk factors, and to analyze whether the new antineoplastic therapies are changing the natural history of this infectious disease. We retrospectively analyzed 46 cases with confirmed LPD-associated PML published from 1958 to 2004. Patients were stratified according to two different time periods: group A included patients diagnosed before 1989, and group B included patients diagnosed since 1990, after introduction of purine analogues.

Nonfatal pulmonary Trichoderma viride infection in an adult patient with acute myeloid leukemia: report of one case and review of the literature.

Trichoderma species have been recognized to be pathogenic in immunosuppressed hosts with increasing frequency. Trichoderma species are responsible for continuous ambulatory peritoneal dialysis associated peritonitis and infections in immunocompromised patients with a hematologic malignancy or solid organ transplantation. Trichoderma longibrachiatum is the most common species involved in these infections.

Platelet dysfunction in primary thrombocythemia using the platelet function analyzer, PFA-100.

We measured platelet function by standard aggregometric tests and by the PFA-100 (Dade Behring, Newark, DE) in samples from 55 patients with primary thrombocythemia (PT) and 26 healthy volunteers. Platelet function was evaluated in platelet-rich plasma by aggregation tests. PFA-100 studies (closure time) were performed in citrated whole blood using collagen-adenosine diphosphate (ADP) and collagen-epinephrine cartridges.

Capillary whole blood testing by a new portable monitor. Comparison with standard determination of the international normalized ratio.

We evaluated a new portable monitor (AvoSure PT PRO, Menarini Diagnostics, Firenze, Italy) developed to test the prothrombin time in capillary blood and plasma by comparing it with the standard laboratory determination. We studied 62 patients receiving acenocoumarol therapy. The international normalized ratio (INR) in capillary blood was analyzed by 2 methods: AvoSure PT PRO and Thrombotrack Nycomed Analyzer (Axis-Shield, Dundee, Scotland).