Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML.

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization.

Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial.

Response loss and development of neutralizing antibodies during long-term treatment with romiplostim in patients with immune thrombocytopenia: a case series.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts resulting from both immune-mediated platelet destruction and inappropriate bone marrow platelet production. Therefore, in patients with ITP failing immunosuppressants/splenectomy, an alternative approach is to enhance platelet production stimulating thrombopoiesis. Studies on the development of recombinant thrombopoietins (rhTPO) were halted as a minority of patients developed an autoantibody that neutralized pegylated rhTPO and also cross-reacted with and neutralized endogenous TPO resulting in thrombocytopenia.

Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation and response to therapy.

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET-related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET-related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus.

Good Outcome for Very High Risk Adult B-cell Acute Lymphoblastic Leukaemia Carrying Genetic Abnormalities t(4;11)(q21;q23) or t(9;22)(q34;q11), if Promptly Submitted to Allogeneic Transplantation, after Obtaining a Good Molecular Remission.

Background And Objectives: Acute lymphoblastic leukaemia (ALL) carrying t(9;22) or t(4;11) genetic abnormalities represents a very high risk subtype of disease (VHR-ALL). Hematopoietic stem cell transplantation (HSCT) remains the best curative option not only for t(4;11) ALL, but also for t(9;22) ALL in the tyrosin-kinase inhibitors era. In the last years, low molecular level of minimal residual disease (MRD) before HSCT was reported as one of the best favourable indexes for survival in ALL.

Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice.

Thrombopoietin mimetics are new treatment options for patients with immune throm-bocytopenia (ITP). Because of their mechanism of action, long-term administration was envisioned in order to maintain effective thrombopoiesis. We report on 30 romiplostim treated patients: 13/27 responders (48%) achieved stable platelet counts on a mean romiplostim dose of 2.

Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia.

Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia.

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism).

Peripheral blood lymphocyte/monocyte ratio predicts outcome in follicular lymphoma and in diffuse large B-cell lymphoma patients in the rituximab era.

Background: Diffuse large B-cell lymphoma is an aggressive lymphoma and a large number of studies have therefore focused on the search for prognostic factors. The same interest concerns FL, for which identification of patients candidates for watch and wait (W&W) strategy is still an option. Studies about the number and type of lymphocytes and monocytes detectable in patients with Hodgkin and non-Hodgkin lymphomas indicate they might affect the pathogenesis and prognosis of these diseases.

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.

High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program.

We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with high-dose methotrexate, fractionated ifosfamide/cyclophosphamide, other drugs in rotation, and intrathecal chemoprophylaxis. One-hundred five patients were treated (median age 47 years, range 17-78 years); 48% had Burkitt leukemia, 25% were older than 60 years, 37% had an Eastern Cooperative Oncology Group performance score >1, and 14% were positive for human immunodeficiency virus.

Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.

Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases.

Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients.

Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.

Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination.

This prospective study compared diagnostic and prognostic value of conventional cytologic (CC) examination and flow cytometry (FCM) of baseline samples of cerebrospinal fluid (CSF) in 174 patients with newly diagnosed aggressive non-Hodgkin lymphoma (NHL). FCM detected a neoplastic population in the CSF of 18 of 174 patients (10%), CC only in 7 (4%; P < .001); 11 patients (14%) were discordant (FCM(+)/CC(-)).

Role of radiotherapy in patients with early-stage diffuse large B-cell lymphoma of Waldeyer's ring in remission after anthracycline-containing chemotherapy.

Consolidation radiotherapy (cRT) in patients with stage I/II diffuse large B-cell lymphoma of the Waldeyer's ring (WR-DLBCL) in complete remission (CR) after induction chemotherapy (CHT) is often associated with relevant acute and chronic toxicity, and its impact on survival remains to be defined. A total of 184 patients in CR after anthracycline-based chemotherapy were retrospectively analyzed: 62 underwent CHT alone (CHT group), while 122 (66%) patients were referred to cRT (CHT + RT group). After a median follow-up of 54 months, 36 patients (20%) experienced relapse: 19% in the CHT group and 20% in the CHT + RT group.

A Case of Atypical Delayed and Prolonged Hematologic Toxicity With Azacitidine in Chronic Myelomonocytic Leukemia (CMML) and Review of Literature.

Hypomethylating drugs are useful and have been approved for the treatment of myelodysplastic syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS, have included only a small number of patients with CMML, and there are just a few specific reports on CMML patients. The Azacitidine is actually authorised for the treatment of CMML patients with 10-29% marrow blasts without myeloproliferative disorder, who are not eligible for haematopoietic stem cell transplantation.

CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease.

The prognostic significance of CD20 expression in acute lymphoblastic leukemia has been investigated in children and adults but is still a subject of debate. The aim of our study was to correlate CD20 expression with clinical-biological characteristics and outcome in 172 Philadelphia chromosome negative patients prospectively treated in a multicenter trial introducing the molecular evaluation of minimal residual disease for therapeutic purposes. We considered 20% as the threshold for CD20 positivity.

Quality of life in elderly patients with essential thrombocythaemia. An Italian multicentre study.

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by elevated platelet counts and increased incidence of thrombosis and haemorrhage. Median age at diagnosis is 65-70 years. Life expectancy is similar to that of the healthy population.

ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned.

Background: BEACOPP, an intensified regimen consisting of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, has been advocated as the new standard of treatment for advanced Hodgkin's lymphoma, in place of the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

Methods: We randomly assigned 331 patients with previously untreated and unfavorable Hodgkin's lymphoma (stage IIB, III, or IV, or an international prognostic score of ≥3 on a scale of 0 to 7, with higher scores indicating increased risk), to receive either BEACOPP or ABVD, each followed by local radiotherapy when indicated. Patients with residual or progressive disease after the initial therapy were to be treated according to a state-of-the-art high-dose salvage program.

A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study).

Background: Invasive fungal infections (IFIs) are considered a major problem among patients undergoing acute leukaemia (AL) induction treatment. PROphylaxis of Fungal invasive Infections in Leukaemia-Caspofungin (PROFIL-C) is a multicentre study aiming to assess the comparative yield of using caspofungin versus standard policy (SP) regimens and the overall impact of IFI in routine clinical care conditions.

Methods: All AL patients receiving IFI prophylaxis according to local SP were prospectively included in the study by Northern Italy Leukaemia Group (NILG) centres.

Results of a lymphoblastic leukemia-like chemotherapy program with risk-adapted mediastinal irradiation and stem cell transplantation for adult patients with lymphoblastic lymphoma.

The therapeutic role of mediastinal radiotherapy and stem cell transplantation (SCT) in lymphoblastic lymphoma (LL) remains controversial. In a risk-oriented design, we adopted a flexible treatment program in which (1) patients with persistent mediastinal abnormality, evaluated by post-induction computed chest tomography, received mediastinal irradiation; and (2) those with persistence of minimal residual disease (MRD), evaluated by MRD analysis of the bone marrow, underwent SCT. Twenty-eight out of 30 patients (T-lineage, n = 24; B-lineage, n = 6) achieved a complete response.

Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib.

Background: Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking.

Patients And Methods: Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study.