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,…

Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt

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…

Treatment of Coagulopathy in Acute Leukemia

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…

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:…

Polymorphonuclear leukocyte
integrin pattern in acute
ischemic stroke

Structure-activity relationship studies of novel heteroretinoids: induction of apoptosis in the HL-60 cell line by a novel isoxazole-containing heteroretinoid.

In a search for retinoic acid receptor (RAR and RXR)-selective ligands, a series of isoxazole retinoids was synthesized and evaluated in vitro in transcriptional activation and competition binding assays for RARs and RXRs. In addition, these compounds were evaluated for their differentiating, cytotoxic, and apoptotic activities. In general, these derivatives showed scarcely any binding affinity and were not active in the transcriptional assay. However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively. On the other hand, c…

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…

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…