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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 343 records · Page 19Linked to original sources
PubMed1989

Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia.

Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy.

Cytarabine↗
PubMed1989

Acute myeloblastic leukemia with t(8;21) following Philadelphia positive acute lymphoblastic leukemia.

A patient with Philadelphia positive (Ph'+) acute lymphoblastic leukemia (ALL), in remission for over 4 years, developed an acute myeloblastic leukemia (AML), M2-type. During the second disease, the blast cells displayed a typical t(8;21)(q22;q22) translocation, in the absence of the Ph' chromosome. This is the first observation in the same patient of two leukemias displaying different cell phenotypes and each associated to one of the most characteristic chromosome changes. Cytogenetic characteristics and clinical aspects of the diseases are suggestive for the occurrence of two independent leukemic processes.

Chromosomes, Human, Pair 21↗
PubMed1988

Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.

We report a prospective study in nine consecutive adult patients with acute promyelocytic leukaemia (APL). The study objective was to assess the prevalence of activation of blood coagulation and/or activation of fibrinolysis in APL. Coagulation and fibrinolytic parameters relevant to the objective included antithrombin III, plasminogen, fibrin/fibrinogen degradation products and alpha-2 antiplasmin activity and antigen levels. The results of this study revealed consistently normal antithrombin III levels, both before and in the course of antileukaemic treatment. Plasminogen levels were slightly decreased or normal. However, a distinct alpha-2 antiplasmin activity deficiency in all patients was observed with levels even reaching zero in three patients, during chemotherapy. Alpha-2 antiplasmin activity levels were consistently lower than the alpha-2 antiplasmin antigen levels. The in vitro binding of alpha-2 antiplasmin activity to fibrin clots was severely reduced which appeared to be due to the reduced alpha-2 antiplasmin plasma levels. Upon crossed-immunoelectrophoresis against alpha-2 antiplasmin antiserum two alpha-2 antiplasmin antigen peaks were observed in the plasma of all nine patients. All abnormalities were reversible 4 d after completion of chemotherapy. In a second series of 12 consecutive APL patients we confirmed the consistency of the alpha-2 antiplasmin activity deficiency and normal antithrombin III plasma levels. In addition Protein C activity and antigen levels were normal or near normal in 10 and reduced in two patients. Thrombin-antithrombin III complexes were increased in 10 and normal in two patients. We conclude that some activation of blood coagulation is present in APL (increased thrombin-antithrombin III complex levels) but its contribution to the coagulopathy seems to be minor (normal antithrombin III and only slightly reduced protein C levels). The observed reduced alpha-2 antiplasmin content of the fibrin clot in vitro may result in vivo in a fibrin clot that is highly susceptible to fibrin degradation, thus aggravating the coagulopathy in APL.

Blood Coagulation↗
PubMed1988

Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect.

We analysed the incidence of graft failure, graft-versus-host disease (GVHD) and relapse of leukaemia in 208 patients undergoing allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia in chronic phase in eight transplant centres in Europe and the United States. 106 patients received unmanipulated donor bone marrow (Group 1) and 102 patients received marrow depleted of T-cells by incubation with the monoclonal antibodies Campath-1 or CT-2 and complement (Group 2). The incidence of graft failure was higher and of GVHD was lower in Group 2 than in Group 1. Relapse of leukaemia occurred more frequently in patients in Group 2 than in Group 1 (17 v. 2, P less than 0.001). Multivariate analysis showed that the following factors were associated with an increased risk of relapse: the use of T-cell depletion, the absence of GVHD and a high platelet count at the time of admission for transplant. The findings support the concept that a graft-versus-leukaemia effect mediated by T-lymphocytes is important for cure of leukaemia after BMT.

Adolescent↗
PubMed1988

Deoxycoformycin in therapy of refractory lymphoid neoplasms.

Knowledge of the vital role of the purine degradative enzyme adenosine deaminase (ADA) in the differentiation of T and B lymphocytes has stimulated interest in the pharmacologic inhibition of ADA as specific cytotoxic therapy for lymphoproliferative diseases. 2'-Deoxycoformycin (DCF) is a tight-binding ADA-inhibitor and has shown activity in T and B cell neoplasms. In this phase-II study, the efficacy and toxicity of DCF in chronic T and B cell neoplasms is investigated. We report the preliminary results of treatment in 27 patients (8 with Sézary syndrome, 11 with B-chronic lymphocytic leukemia (CLL), and 8 with hairy cell leukemia (HCL)), who were refractory to conventional therapy. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Three of the 8 patients with Sézary syndrome and 3 of the 11 patients with B-CLL attained a partial remission. One complete and 7 partial remissions have been achieved thus far in the 8 patients with HCL refractory to interferon alpha treatment. Other than nausea in 10 patients (mainly grade 1 and 2), transient skin rash in 4 patients and Herpes infections in 4 patients (mainly grade 2), no other major toxicities were observed. Thus DCF is highly active in hairy cell leukemia that did not respond to interferon alpha, and shows moderate activity in refractory Sézary syndrome and B-CLL.

Antineoplastic Agents↗
PubMed1987

Late multifocal gliomas in adolescents previously treated for acute lymphoblastic leukemia.

Three of 37 adolescents in long-term remission from childhood acute lymphoblastic leukemia (ALL) developed malignant multifocal gliomas several years after completing treatment that included central nervous system (CNS) prophylaxis with radiation (RT) and intrathecal methotrexate (IT-MTX). No recurrence of the leukemia was evident when the CNS tumors were discovered. Seventeen other similar cases have been recorded. The occurrence of second malignancies is reviewed in the context of this development and of the oncogenic effects of radiation. It is probable that prolonged exposure to IT-MTX may have had a synergistic effect with radiation in contributing to the unusual incidence of glial tumors in these patients.

Adolescent↗
PubMed1987

Secondary acute non lymphoid leukemia in patients treated for non Hodgkin's lymphoma: no risk of therapy-related ANLL after PROVECIP schedule.

The present study was undertaken to evaluate the frequency, characteristics and actuarial risk of secondary acute non lymphoid leukemia (s-ANLL) in 141 patients treated for non Hodgkin's lymphoma with different modalities. One hundred and twenty-four patients received chemotherapy according to PROVECIP protocol. Of these, 15 also received as induction treatment a local nodal irradiation and 33 an extended field radiotherapy. Seventeen out of 141 were treated by total body irradiation. Of these, 15 relapsed and received salvage chemotherapy. Sixteen of the 124 patients treated with PROVECIP also underwent different chemotherapeutic programs as salvage treatment. Of the entire population studied, 2 patients developed an s-ANLL, 45 and 63 months after diagnosis of NHL. The type of treatment significantly affected the occurrence of s-ANLL, since both leukemias occurred in patients treated with total body irradiation, given alone or followed by chemotherapy. The actuarial risk at 8 years was 5.24% in the whole group, whereas it greatly increased in the group of patients treated with total body irradiation (24%). Conversely, no risk was found in the group treated with PROVECIP, alone, with additional chemotherapy, or with associated local or extended field radiotherapy.

Acute Disease↗
PubMed1987

Evaluation of the nature of mildly prolonged prothrombin times.

Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII-/R). Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi. We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency. On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency. In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.

Adolescent↗
PubMed1987

Two murine monoclonal antibodies to peripheral blood monocyte differentiation antigens discriminate within M5 acute non-lymphoid leukemia (ANLL) cells.

Two murine monoclonal antibodies (MoAbs), LAM3 and LAM7 of the IgG1 isotype, which were produced by immunization with normal peripheral blood monocytes (PBM), were assayed in their specificity by indirect immunofluorescence against a panel of normal as well as leukemic cells. Both LAM3 and LAM7 were reactive with PBM while LAM3 also recognized platelets. Neither MoAb showed reactivity with erythrocytes, granulocytes, or resting and mitogen activated B and T lymphocytes. The reactivity with bone marrow cells correlated with the degree of monocyte contamination. Among the 62 cases of leukemia tested, which included three cases of B-CLL, 19 cases of ALL, and 40 cases of ANLL, both MoAbs reacted highly homogenously only with M5b ANLL cells. These findings indicate that the two MoAbs, which recognize two distinct epitopes, represent useful markers in the differential diagnosis of M5b ANLL.

Acute Disease↗