0000000000122508
AUTHOR
Maurizio Musso
Supportive care services in hemato-oncology centers: a national survey
Background: In the field of hemato-oncology, there is paucity of data assessing models of integration between hemato-oncology and other partner specialties. The aim of this national survey was to gather information about the status of the integration of this kind of activity in hemato-oncologic units existing in Italy. Methods: A national telephone survey was conducted to gather information about the status of the integration of hemato-oncologic and supportive care/anesthesiological services. From the national registry of hemato-oncology units, 149 centers were contacted by phone and a dedicated doctor was identified to gather information about the center through a telephone interview. Resu…
Erythromycin reverses the daunomycin resistance of MEL-DRTL cells
Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials.
In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%…
High BCR-ABL/GUS(IS) levels at diagnosis of chronic phase CML are associated with unfavorable responses to standard-dose imatinib
Abstract Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. Experimental Design: We correlated BCR–ABL/GUSIS and BCR–ABL/ABL transcripts at diagnosis with the outcome—defined by the 2013 European LeukemiaNet recommendations—of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR–ABL/GUSIS and BCR–ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transform…
68 O - Maintenance low-dose (LD) oral idarubicin (oIDA) in elderly patients (pts) with acute myelogeneous leukemia (AML)
IDA by i.v. route. especially in combination with cytosine arabinoside (Ara-C). proved quite effective for intensive chemotherapy of AML However, persisting controversies on aggressive/intensive versus “ottenvated” regimens for elderly AML pts emphasize the interest of olDA in this latter setting (ct M.R. Howard et al and M.J. Keating. Clin. Drug Invest. 1995; 9. Suppl. 2: 16–38) A 69% complete response (CR) rate was recentty reported (F. Leoni et al Br. J. Hoematol 1995; 90: 169–174) among 25 elderly AML pts (> 60 yrs old) with an “attenuated” dose of IDA, i.e. 8 mg/m2 i.v. d, 1. 3, and 5. plus Ara-C 200 mg/m2 by continuous i.v. infusion (ClV) d, 1–7, and etoposide (VP-16) 60 mg/m2 i.v. d,…
Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients
The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583 KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3 lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categori…
Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib
A reduction in BCR-ABL1/ABL1IS transcript levels to <
Differences among young adults, adults and elderly chronic myeloid leukemia patients
Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…
Granulocyte integrins before and after activation in acute ischaemic stroke.
We examined in 19 subjects with acute ischaemic stroke (AIS) the PMN integrin pattern (CD11a, CD11b, CD11c, CD18), using indirect immunofluorescence and adopting a flow cytometer, at baseline and during activation, prolonged for 5 and 15 min, with 4-phorbol 12-myristate 13-acetate (PMA). At baseline, an increase in the expression of CD11c and CD18 and a decrease in the CD11b were evident in AIS subjects compared to normals. After activation, we found in normals a constant and significant increase of all PMN adhesive molecules, while in AIS subjects, we found an increase in CD11b and CD18, a decrease in CD11a and no variation in CD11c. While the basal upregulation of CD11c and CD18 may depen…
Comparative activity of idarubicin and idarubicinol in combination with cyclosporin A in multidrug-resistant leukemia cells
4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good cytotoxic activity in vitro against tumor cell lines displaying the multidrug-resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol (2HIDA) and, in this form, seems to exert its antitumoral activity in vivo. Recent studies have shown that 2HIDA has tumoricidal activity similar to that of the parent drug when tested in vitro in sensitive neoplastic cells. In this work we compared in vitro the effects of IDA and 2HIDA used alone and in combination with 2 microM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R and in their sensitive parent cell lines FLC and K562. IDA and 2HI…
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
© 2018 The Authors.
Transfusion‐transmitted malaria of plasmodium malariae in palermo, sicily
Transfusion-transmitted malaria (TTM) is a rare occurrence with serious consequences for the recipient. In non-endemic areas, the incidence of transmission of malaria by transfusion is very low. We report a clinical case of transfusion-transmitted malaria due to Plasmodium malariae, which happened in a patient with acute hemorrhagic gastropathy. Case presentation: In April 2019, a 70-year-old Italian man with recurrent spiking fever for four days was diagnosed with a P. malariae infection, as confirmed using microscopy and real-time PCR. The patient had never been abroad, but about two months before, he had received a red blood cell transfusion for anemia. Regarding the donor, we revealed t…
Treatment of Coagulopathy in Acute Leukemia
Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials.
The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P &lt; 0.0001), older age (HR = 1.72; P &lt; 0.0001), and prior lenalidomide exposure (…
Oral Idarubicin in Maintenance Therapy of Acute Myeloid Leukemia
More than half of all acute myeloid leukaemia (AML) patients are over 60 years. The disease free survival (DFS) and overall survival (OS) rate of these patients is poor. These unsatisfactory results are associated with adverse cytogenetic characteristics, prior myelods-plasia, adverse phenotypic features, MDR and BCL2 overexpression. Furthermore a large fraction of patients achieving CR early relapses. This is due to two factors: acquired tumor cell drug resistance and tumor re-growth. Maintenance therapy could provide a means to keep leukemic growth under control. We enrolled 31 elderly previous responder patients to standard induction therapy to receive maintenance oral IDA 3mg/m2 daily d…
Polymorphonuclear integrins, membrane fluidity, and cytosolic Ca(2+) content after activation in essential hypertension.
Abstract —The purpose of this research was to obtain further information about the role of polymorphonuclear leukocytes in essential hypertension. These cells could be involved in the pathogenesis of organ injury. Thirty subjects (14 men and 16 women) with essential hypertension were enrolled. In these subjects we determined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate and N -formyl-methionyl-leucyl-phenylalanine, the polymorphonuclear leukocyte membrane fluidity, obtained by labeling the cells with 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene, cytosolic Ca 2+ concentration, obtained by marking the cells with Fura 2-AM, and integrin pattern (C…
Polymorphonuclear leukocyte integrin pattern, at baseline and after activation, in type 2 diabetic subjects with macrovascular complications.
In vascular atherosclerotic disease and in diabetes mellitus few studies have evaluated the polymorphonuclear leukocyte (PMN) adhesion molecule pattern. In this study we examined the PMN integrin expression at baseline and after activation in controls and type 2 diabetic subjects with macrovascular complications (MVC). We enrolled 21 subjects with type 2 diabetes mellitus and macrovascular complications, localized in peripheral, coronary and cerebral sites. The patients had peripheral occlusive arterial disease, chronic cerebrovascular disease or coronary heart disease. We evaluated the expression of some PMN integrins (CD11a, CD11b, CD11c, CD18), using flow cytofluorimetry, at baseline and…
Feasibility, Tolerability and Efficacy of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real-Life Survey of the Sicilian Myeloma Network
Background: The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known about safety and efficacy of KRd outside a clinical trial context. Methods: Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers. Results: Median age was 62 years
Sustained Responses and Resistance to Imatinib Mesylate in the First 173 Chronic Myeloid Leukemia Patients Accrued by the SCREEN Multicenter Study: First Interim Report
Abstract Abstract 4276 Introduction Imatinib mesylate (IM) has shown unprecedented effectiveness in the treatment of Chronic Myeloid Leukemia (CML) patients (pts) in the chronic phase of the disease. As most of the data concerning the efficacy of the drug derive either from a single sponsored trial or from single institution reports, we decided to accrue all CML pts diagnosed in the Italian region of Sicily to the observational SCREEN (Siciliy CML Regional Enterprise) study, to evaluate the hematological, cytogenetic and molecular responses of this unselected population to IM. Patients and Methods Although the study is still ongoing, 173 consecutive CML pts have been enrolled between Januar…
High BCR-ABL/GUSIS Levels At Diagnosis Are Associated With Unfavorable Responses To Imatinib
Abstract The approval of three tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated an urgent need for molecular parameters predictive of unfavorable therapeutic outcomes. Recent evidence suggests that failure to achieve early molecular responses (i.e. BCR-ABL/ABLIS levels <10% after 3 months or <1% after 6 months of TKI treatment) results in inferior rates of both overall and progression-free survival. With the current study, we wanted to establish if high BCR-ABL transcripts at diagnosis would be associated with unfavorable responses to Imatinib Mesylate (IM). Thus, we correlated quantitative determinations of BCR-ABL levels …
Haematopoietic stem cell transplantation for vasculitis including Behçet's disease and polychondritis: a retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature
Objective: To evaluate the feasibility of haematopoietic stem cell transplantation (HSCT) in vasculitis. Methods: This is a retrospective analysis of patients who had received HSCT for vasculitic diseases and have been reported to the European League Against Rheumatism autoimmune disease or European Bone Marrow Transplantation ProMISe databases. Information about the disease and outcome was obtained by a questionnaire sent to the referring centres. Response of the disease to HSCT was defined as partial or complete responses according to the ability to reduce immunosuppression after HSCT. In addition, the Medline database was searched for reports on HSCT in patients with vasculitis. Results:…
Impact of Cumulative Dose of Carfilzomib in Combination with Lenalidomide and Dexamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real Life Survey of the Sicilian Myeloma Network
Abstract Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM. The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd), leading to approval of K for RRMM. However, little is known about safety and efficacy of KRd outside a clinical trial context. Experimental design and aims: In 11 Sicilian Centers belonging to the Sicilian Myeloma Network, from November 2016, when KRd regimen was approved in Italy, to June 2018, 103 consecutive RRMM patients (previ…
Successful treatment of resistant thrombotic thrombocytopenic purpura/hemolytic uremic syndrome with autologous peripheral blood stem and progenitor (CD34+) cell transplantation
The first-line treatment of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS syndrome) induces a response and survival rate of approximately 85%, even if a considerable number of patients relapse; nevertheless, a number of these patients are resistant to conventional management. Immunoablation followed by stem cell transplantation has been shown to be capable of inducing remissions in a large spectrum of experimental autoimmune disorders. We report here the case of a 20-year-old male patient with the TTP-HUS syndrome who was resistant to conventional treatment and was transplanted with autologous immunoselected CD34+ PBPC after conditioning with cyclosphosphamide, anti…
High BCR-ABL Levels At Diagnosis Are Associated with Unfavorable Responses to Imatinib Mesylate.
Abstract Abstract 2790 The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of Chronic Myeloid Leukemia (CML) has generated a need for early molecular parameters associated with inadequate responses to Imatinib Mesylate (IM). Recent evidence suggests that CML patients presenting BCR-ABL/ABLIS levels >10% after 3 months of IM or >1% after 6 months of treatment have inferior outcomes in terms of both overall survival (OS) and progression-free survival. We wanted to establish if high BCR-ABL transcripts at diagnosis would also be associated with unfavorable responses to IM. To this end, we correlated quantitative determinations of BCR-ABL measu…
Pre-Emptive Treatment with Cidofovir for Cytomegalovirus Antigenemia in Autologous Bone Marrow Recipient and CLL Patients on Therapy with Alemtuzumab.
Abstract Cytomegalovirus (CMV) is an important cause of morbidity and mortality in patients who have undergone severe immunosuppressive therapy. Ganciclovir continues to be the first choice for pre-emptive therapy, but it needs multiple intravenous daily administration for three weeks and may cause myelosuppression. Cidofovir is a non myelotoxic nucleotide analogue effective against CMV; its favourable pharmacokinetic profile allows a once-a-week dosing. We reviewed a database on 110 consecutive Autologous Stem Cell Transplant (ASCT) and that of 15 Chronic Lymphocytic Leukemia (CLL) patients treated with alemtuzumab. All patients were virologically monitored by quantification of pp65 antige…
Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome.
Immunoablation followed by allogeneic stem cell (SC) transplantation has been shown to be capable of curing a large spectrum of experimental autoimmune disorders, hereditary and/or induced. Superimposable results, albeit with some exceptions, have been obtained in human patients affected by coincidental autoimmune and blood diseases. However, both because of encouraging experimental results and of the procedure's greater safety, autologous SC are being increasingly utilized worldwide. Case reports are being collected in the registry of the European Group for Blood and Marrow Transplantation (EBMT)/European League against Rheumatism (EULAR) Autoimmune Disease Stem Cell Project. Among the se…