Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults

BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.)

EPIDEMIOLOGY OF CARBAPENEM RESISTANT KLEBSIELLA PNEUMONIAE INFECTIONS IN MEDITERRANEAN COUNTRIES

Infections by Carbapenem-Resistant Enterobacteriaceae (CRE), in particular carbapenem-resistant Klebsiella pneumoniae (CRKp), are a significant public health challenge worldwide. Resistance to carbapenems in enterobacteriaceae is linked to different mechanisms, in particular the production of different types of enzymes including KPC, VIM, IMP, NDM, and OXA-48. Despite several attempts to control the spread of these infections at local and national level, epidemiological situation for CRKp had worsened in the last years in the Mediterranean area. The rate and types of CRKp isolates greatly differ in the various Mediterranean countries. KPC-producing K.pneumoniae is diffused particularly in the European countries bordering the Mediterranean sea and is actually endemic in Greece and Italy. On the contrary, OXA-48-producing K.pneumoniae is endemic in Turkey and Malta, and diffused at inter-regional level particularly in some north African and Middle East countries. The spread of these multiresistant pathogens in the world and the Mediterranean countries has been related to various epidemiological factors including the international transfer of patients coming from endemic areas

CPX-351: An Old Scheme with a New Formulation in the Treatment of High-Risk AML

Therapy-related acute myeloid leukemia (t-AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) represent aggressive diseases characterized by a dismal prognosis if compared with de novo acute myeloid leukemia, especially in older patients. In these AML subsets, standard chemotherapy regimens produce poor response rates and unsatisfactory outcomes. Historically, conventional approaches consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the “3+7” regimen. Several attempts have been conducted to ameliorate this combination regimen but inconsistent improvements in response rates and no significant changes in overall survival have been observed, until the recent introduction of targeted molecules. A liposomal formulation of traditional chemotherapy agents cytarabine and daunorubicin, termed CPX-351, enhances pharmacodynamics and synergistic effects through the maintenance of the optimal 5:1 molar ratio, which extends the treatment’s half-life and increases the bone marrow tropism of the drug. The use of CPX-351 in newly diagnosed AML-MRC and t-AML patients aged 60–75 years has demonstrated superior remission rates compared to conventional chemotherapy and improvements in event-free and overall survival. Recently, published data from a 5-year follow-up highlighted evidence that CPX-351 has the ability to produce and contribute to long-term remission and survival in older patients with newly diagnosed high-risk/secondary AML. Future perspectives include evaluation of dose intensification with CPX-351 in high-risk settings, combining this agent with targeted therapies, and better understanding the mechanism of improved responses in t-AML and AML-MRC. In this review, we will examine the role of CPX-351 inside the new AML therapeutic scenario and how its employment could potentially modify the treatment algorithm of high-risk and elderly patients with AM

The Eutos long-term survival score accurately predicts the risk of death in chronic myeloid leukaemia patients treated outside of clinical trials

No abstract availabl

A case of late isolated ovarian relapse of acute lymphoblastic leukemia after an allogeneic stem cell transplant.

We report the case of a 30-year-old Caucasian female who had an isolated ovarian relapse 13 years after a diagnosis of acute lymphoblastic leukemia (ALL) and 8 years after an allogeneic peripheral blood hematopoietic stem cell transplant (HSCT)

ARA-C, IDARUBICINE AND GENTUZUMAB OZOGAMICIN (AIM) AS SALVAGE TREATMENT IN ADVANCED ACUTE MYELOID LEUKEMIA PATIENTS

<p>Long-term survival of relapsed/refractory acute myeloid leukemia (AML) remains a major problem, particularly in patients not eligible for transplantation.</p><p>We hereby evaluated the feasibility and efficacy of adding Gemtuzumab Ozogamicin to salvage chemotherapy (Ara-C, Idarubicine, Peg-Filgrastim) in relapsed/refractory AML. The main endpoints were: the rate of complete remissions (CR) and the proportion of patients capable of undergoing a stem cell transplant.</p><p>Fourty-two patients were enrolled. The overall CR rate was 76% and no induction deaths were reported. In 56% of patients, a transplant procedure could be performed. The treatment schedule proved feasible and well tolerated, providing a high CR rate and a useful bridge to transplant.</p&gt