GEMTUZUMAB OZOGAMICIN COMBINED WITH INDUCTION CHEMOTHERAPY IN YOUNG ADULTS WITH ACUTE MYELOID LEUKEMIA: REVIEW AND PERSPECTIVES.

Progress in treatment of acute myeloid leukemia (AML) is slow. Many new agents have been tested, but few were approved. Gemtuzumab Ozogamicin (GO) is a new AML-targeted drug that is composed by a monoclonal antibody targeting a surface antigen of myeloid leukemic cells (CD33) combined with a potent cytotoxic (calicheamicin). We review here the studies of GO in AML, including an update of the Italian studies, and we trace back the story of a drug that was developed 15 years ago and, regrettably, is no longer available for the treatment of AML, with the exception of Japan. GO was approved by the US FDA for the second-line treatment of AML in the elderly, and was shown by several European large prospective and randomized studies to be active also in first line, both alone, but particularly in combination with standard chemotherapy. Regrettably, a registration study that was performed in US could not confirm the superiority of GO and chemotherapy on chemotherapy alone, and the drug was withdrawn. The differences among the US and the European studies are discussed. The profile of the AML patients who are expected to benefit more by the reintroduction of GO is proposed: first-line, less than 60 years old, CD33 expressed in more than 20% leukemic cells, low/intermediate cytogenetic risk, and low expression of the PGP multidrug resistance protein

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

Introduction: Patients reported outcome (PRO) are still under-used in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), though data on the correlation between quality of life (QoL) and therapeutic efficacy are increasingly known. Chronic low-grade toxicities can reduce patient's QoL and negatively impact on adherence.Areas covered: This review will focus on the role of QoL questionnaires in patients with CML, receiving imatinib or newer TKIs (dasatinib, nilotinib, bosutinib, ponatinib). Physicians tend to underestimate the impact of TKI-related symptoms, in particular fatigue, that negatively affect QoL and can be a reason of poor adherence to therapy, with detrimental effect on long-term response. Few studies pointed out the role of PRO in CML, and there is paucity of questionnaires specifically designed for CML patients.Expert commentary: We recommend a wider use of PRO to join the pursuit of a rapid and deep responses with an optimization of QoL

The OPERA magnetic spectrometer

The OPERA neutrino oscillation experiment foresees the construction of two magnetized iron spectrometers located after the lead-nuclear emulsion targets. The magnet is made up of two vertical walls of rectangular cross section connected by return yokes. The particle trajectories are measured by high precision drift tubes located before and after the arms of the magnet. Moreover, the magnet steel is instrumented with Resistive Plate Chambers that ease pattern recognition and allow a calorimetric measurement of the hadronic showers. In this paper we review the construction of the spectrometers. In particular, we describe the results obtained from the magnet and RPC prototypes and the installation of the final apparatus at the Gran Sasso laboratories. We discuss the mechanical and magnetic properties of the steel and the techniques employed to calibrate the field in the bulk of the magnet. Moreover, results of the tests and issues concerning the mass production of the Resistive Plate Chambers are reported. Finally, the expected physics performance of the detector is described; estimates rely on numerical simulations and the outcome of the tests described above.Comment: 6 pages, 10 figures, presented at the 2003 IEEE-NSS conference, Portland, OR, USA, October 20-24, 200

The Role of Meningioma-1 (Mn1) Gene as Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: A Concise Review

Molecular markers are necessary for prognostic stratification and monitoring of Minimal Residual Disease (MRD) in Acute Myeloid Leukemia (AML) [1,2]. Cytogenetic aberrations have long been recognized as the most important prognostic variable in AML, and are still the major determinant for post-remission therapy [3]. Unfortunately, only 50-60% of AML patients present an abnormal karyotype at diagnosis, while the remaining cases display a Normal Karyotype (NK). NK AML patients are generally included in an “intermediate risk” prognostic group, that is however characterized by a heterogeneous clinical course. To stratify prognosis of NK AML patients, numerous studies have led, in the last decade, to the introduction of different molecular markers such as FLT3, NPM1, BAALC and CEBPA [4-7]. Still, their use to monitor disease, either defining remission status and detecting relapse as early as possible, is still somehow controversial, due to fluctuations during disease course, low incidence rates in AML and sensitivity of the technologies detecting the single marker [8-10]. These limitations have, to date, precluded a timely and precise quantification of disease in NK AML patients, thus preventing from a complete individualization of post-remission therapy and early treatment in case of impending relapse. In other words, in NK AML it has not been reached the precision achieved in BCR/ABL-positive chronic myeloid leukemia and PML/RAR alpha mutated acute promyelocytic leukemia

Real-Time TDM-based optimization of continuous-infusion meropenem for improving treatment outcome of febrile neutropenia in oncohaematological patients: Results from a prospective, monocentric, interventional study

Objectives: To assess the role that real-Time therapeutic drug monitoring (TDM)-guided optimization of continuous-infusion (CI) meropenem may have in maximizing empirical treatment and in preventing breakthrough infection and/or colonization with carbapenem-resistant Enterobacteriaceae (CRE) among oncohaematological patients with febrile neutropenia (FN). Methods: A monocentric, interventional, prospective study was conducted. The pharmacodynamic (PD) target was a steady-state meropenem concentration-To-MIC ratio (Css/MIC) of 4-8. The primary endpoint was 14 day all-cause mortality. The secondary endpoint was the prevalence of CRE colonization in rectal swabs of patients rehospitalized within 3months. Results: Among the 75 patients enrolled, most (56%) had AML, almost half (37/75, 49.3%) underwent HSCT and one-Third (32%) received meropenem as monotherapy. Meropenem dosages were adjusted in 30.1% of TDM reassessments. Gram-negative infections were microbiologically documented in 20.0% of patients. All of the 12 patients having infections caused by in vitro meropenem-susceptible pathogens attained the desired PD target and were cured. Three patients had infections caused by in vitro meropenem-resistant pathogens. Two of these achieved a Css/MIC target of 1 and were cured; the other one achieved a suboptimal PD target (0.59) and died. The 14 day all-cause mortality (10.7%) was significantly associated, at multivariate regression, with HSCT (OR 0.086, 95% CI 0.008-0.936, P = 0.044) and with augmented renal clearance (OR 10.846, 95% CI 1.534-76.672, P = 0.017). None of the patients who had hospital readmissions in the 3month follow-up (63/75) had CRE colonization in rectal swabs. Conclusions: Real-Time TDM-guided CI meropenem may be a useful approach for attaining adequate exposure and preventing CRE emergence in FN oncohaematological patients