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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 379 records · Page 21Linked to original sources
PubMed1986

Hairy cell leukemia: preliminary results with alpha 2 (r) interferon.

Ten patients with hairy cell leukemia are being treated at our institution with a therapeutic schedule of alpha 2(r) interferon (2 X 10(6) IU/m2 s.c. three times per week). Five patients underwent splenectomy from 4 to 108 months before treatment; nonsplenectomized patients had spleens palpable 6 to 12 cm UCM. According to Quesada's response criteria, at the sixth month of therapy, one patient was considered a complete responder, 8 partial responders and one a minor responder, with no differences between splenectomized and nonsplenectomized patients. In nonsplenectomized patients the spleen returned to normal. Our data confirm that interferon, even at low dosages, is a very effective approach for hairy cell leukemia. No evidence was found to contraindicate such therapy.

Adult↗
PubMed1986

Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis.

We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C alpha 1 locus and over-expressed in two abnormal mRNAs of approximately 2.0 and 2.8 kb. Conversely, in two cases of B-cell lymphoma progressed into leukemia the c-myc locus was translocated intact in its coding and 5'-flanking region into an Ig region different from C alpha 1, and over-expressed in two normal mRNA species. Cloning and sequencing of the breakpoint region on chromosome 14q+ from one of the two B-ALL cases showed that the myc gene is truncated 1077 nucleotides upstream from the translation start site, and rearranged in the opposite transcriptional orientation into an Ig class-switch segment approximately 4.8 kb upstream from the C alpha 1 gene. The c-myc anti-sense strand contains two class-switch recombination consensus sequences in the immediate boundaries of the breakpoint on chromosome 8: this allows us to postulate that an erroneous, class-switch-like recombination between Ig and myc sequences gave rise to the chromosomal translocation. Furthermore, we report 13 point mutations clustered in a region spanning from the first intron to the second exon of the translocated c-myc gene, five of which cause amino acid changes leading to an abnormal myc protein. This is the first evidence of mutations in a translocated c-myc in primary tumor cells.

Adolescent↗
PubMed1986

Decreased NK activity in hairy cell leukemia (HCL): an analysis at the cellular level.

Peripheral blood lymphocytes (PBL) of eleven patients with Hairy Cell Leukemia were studied for surface phenotype and for NK activity against the K 562 cell line (using both the standard 51Cr Release Assay and the Single Cell Cytotoxicity Assay on poly-L-lysine coated coverslips). A significant reduction in NK activity, target binding cells (TBC) and NK active cells (NKa) was detected. In some cases however, despite a very low percentage of NKa, residual NK activity was observed, suggesting an efficient recycling capacity.

Adult↗
PubMed1986

Evaluation of therapeutic modalities in the control of Hodgkin's disease.

The results achieved in three different studies carried out on patients affected by Hodgkin's disease are discussed. In study No. 1, 58 patients with pathological Stage I-II were treated with only a "Mantle" field irradiation. The complete remission (CR) rate was 98% with an actuarial overall survival of 90%, and a median of follow-up of 80 months. Thirty-one percent of patients relapsed. In study No. 2, 42 patients were randomly allocated to receive only MOPP chemotherapy versus extended field irradiation; CR rate was 68 and 95%, respectively (p less than 0.05). The overall survival rate was 100% in the radiotherapy group and 82% in the MOPP group. No relapses have been observed in patients treated with MOPP. In study No. 3, 218 patients affected by advanced Stage HD were randomly treated with 6 cycles of MOPP chemotherapy versus 6 cycles of ABVD chemotherapy. In the MOPP group the CR rate, the relapse-free survival rate (RFS), and overall survival (OS) rates at 60 months were 77, 68, and 76% respectively, whereas, in the ABVD group the CR, the RFS, and OS rates at 60 months were 75, 77 and 80% respectively, (p less than 0.05). These data and statistical comparisons are analyzed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Expression of cellular oncogenes in primary cells from human acute leukemias.

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.

DNA, Neoplasm↗
PubMed1986

Pipobroman therapy of essential thrombocythemia.

We report our results with pipobroman (PB) therapy in patients with essential thrombocythemia (ET). 21 consecutive untreated patients were treated with PB from 1975 to 1984. PB was given at a dose of 1 mg/kg/d until platelet count dropped below 600 X 10(9)/l. In 18 patients (86%) a hematological remission was obtained. Median duration of induction phase was 49 d. In all cases a maintenance regimen was required at a dose ranging from 0.2 mg/kg/d to 0.5 mg/kg/d, according to platelet number. Follow-up of responder patients ranged from 6 to 108 months (median 17 months). Treatment was well tolerated and we observed only a very moderate and transient hematological toxicity. No patient had relapsed or developed secondary neoplasms at the time of writing. Median survival time of all patients was 24 months (range 10-115).

Adult↗
PubMed1986

Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.

This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Comparison between subcutaneous and intravenous DDAVP in mild and moderate hemophilia A.

Sixteen patients with mild and moderate hemophilia were given Desmopressin (DDAVP) subcutaneously in the absence of any actual bleeding. The response to the drug - in terms of factor VIII coagulant activity rise - became apparent 15 min after the injection, reaching the maximal response after one hour (means 3.2 times the baseline levels; SD 1.21). This response was not different from that elicited using the intravenous route in 18 hemophiliacs of comparable severity after the same time interval. No local or general side-effects were recorded after the subcutaneous administration of DDAVP. We therefore conclude that the subcutaneous route adds further evidence to the reliability of this alternative treatment in mild factor VIII deficiencies, thus making home treatment with this vasopressin analogue possible.

Deamino Arginine Vasopressin↗
PubMed1985

Superinfections during antimicrobial treatment with betalactam-aminoglycoside combinations in neutropenic patients with hematologic malignancies.

The frequency, etiology and risk factors of superinfections during and/or within one week after antibiotic therapy with betalactam-aminoglycoside combinations were evaluated in 631 patients with hematologic malignancies admitted to the Institute of Hematology of Rome from January 1982 to December 1984. 356 patients (56%) developed 402 episodes of proven or presumed infection. Of these patients, 78 developed 102 superinfections. Overall, superinfections responded less satisfactorily to antibiotic therapy than the primary febrile episodes (63% vs. 85%). The distribution of etiologic agents of superinfections differed from those responsible for primary infections, since fungi and anaerobes (especially Clostridium difficile) were mostly isolated after antibiotic therapy had begun. Moreover, among aerobic bacteria, frequently antibiotic-resistant species, such as Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococcus epidermidis were the leading etiologic agents of superinfection. The risk of superinfection appeared to increase with the depth and persistence of granulocytopenia. On the other hand, the length of hospitalization, length of previous antibiotic therapy, previous chemoprophylaxis and presence of indwelling venous catheter did not affect the risk of superinfection.

Adolescent↗
PubMed1985

Cryopreserved autologous bone marrow infusion following high dose chemotherapy in patients with acute myeloblastic leukemia in first relapse.

Thirteen patients with AML in first relapse were treated with high dose combination chemotherapy followed by cryopreserved autologous bone marrow transplantation (ABMT). The first four patients received the COATA-Roma regimen, consisting of CTX, VCR, CA, 6-TG and ADM; nine additional patients received the BAVC regimen consisting of BCNU, AMSA, VP-16 and CA. A median of 1.6 X 10(8) fractionated nucleated bone marrow cells/kg body weight were reinfused. The median of GM-CFU-C recovered was 4.7 X 10(4)/kg. Out of 13 patients, 10 (76.9%) achieved CR, 3 had profound aplasia and died from hemorrhagic or infectious complications. Of the 10 patients who achieved CR, 1 died after 1 week from heart failure, 5 relapsed respectively 17, 20, 21, 21, 42, weeks after ABMT, 4 are still in CR after 2+, 14+, 17+, and 120+, weeks. Of the 9 patients treated with BAVC regimen, 8(88.8%) achieved CR. Four patients relapsed after a median of 19.7 weeks and 4 are still in complete remission. Of interest is the fact that the second complete remission of one patient is longer than the first one, despite the fact that marrow was not purified by any in vitro treatment. In conclusion we can say that BAVC regimen is highly effective in obtaining second complete remission in patients with AML and prolonged disease free survival can be achieved at least in a small number of cases.

Adolescent↗
PubMed1985

Serum bactericidal activity as a therapeutic guide in severely granulocytopenic patients with gram-negative septicemia.

The peak and trough levels of bactericidal activity of the serum of 74 severely granulocytopenic patients (less than or equal to 500 polymorphonucleates per microliter) with hematologic malignancies and Gram-negative septicemia were measured using the patient's infectious organism and serum containing the given antibiotics. When the peak titer of bactericidal activity in the serum was greater than 1:8 the septicemia was cured in more than 90% of the cases. However, in order to achieve a satisfactory rate of cure, patients with less than 100 polymorphonucleates/microliter required higher peak levels than patients with 100-500 polymorphonucleates/microliter. Serum bactericidal activity was influenced by the in vitro susceptibility of the offending pathogen and by the presence of in vitro synergism between the given antibiotics. These two variables showed a correlation with the clinical outcome that proved to be increasing with the degree of granulocytopenia. Furthermore, synergistic combination of the antibiotics appeared essential when the in vitro susceptibility shown by the offending pathogen was moderate. These data suggest (i) that determination of the bactericidal activity of the serum may prove to be a useful method to predict the clinical outcome in severely granulocytopenic patients with Gram-negative septicemia; and (ii) under the same conditions, antibiotic combinations that have demonstrable in vitro synergy against the offending pathogen should be given the utmost consideration.

Agranulocytosis↗
PubMed1985

A case of Burkitt lymphoma-L3ALL with t(8;14) translocation, developed 10 years after Hodgkin's disease.

We report the case of a 38-year-old man, previously treated for Hodgkin's disease (HD) with chemo-radiotherapy who, 10 years later, developed a Burkitt lymphoma (BL) as a tumour mass of the ascendent colon and regional lymph nodes and, subsequently, on leukaemic bone-marrow cells, on the basis of histological, immunological (B phenotype, IgM-lambda) and cytogenetic, translocation t(8;14) features. The patient died a few days later; at autopsy no evidence of HD was found. This is the 2nd case of BL developing after HD so far described. The relationship between the 2 diseases is discussed and the importance of the immunodepression in the pathogenesis of the secondary Burkitt lymphoma is emphasized.

Adult↗
PubMed1985

Childhood abnormal expansion of large granular lymphocytes.

An expansion of large granular lymphocytes (LGL) in the peripheral blood (PB) of a 10-year-old child is described. After a long history of uncertain hematological diagnosis and chemotherapeutic regimens and 2 years after any kind of therapy, the child showed in PB an expansion of LGL E-rosette+, OKT3+, OKT8+, Leu7+. Cytotoxic activities showed high natural killer activity and an increase of PHA-induced cytotoxicity. Histological findings in the spleen, abdominal lymph nodes and bone marrow excluded a lymphoproliferative disease, but liver biopsy revealed a chronic aggressive hepatitis.

Bone Marrow Examination↗
PubMed1985

Turnover of alpha-2-antiplasmin in patients with acute promyelocytic leukemia.

Patients with acute promyelocytic leukemia have a bleeding disorder which was thus far explained by a coagulopathy based on diffuse intravascular coagulation (DIC). We observed severe alpha-2-antiplasmin deficiency in a consecutive series of such patients. We postulate proteolysis rather than DIC, also because of increased turnover of 125I-alpha-2-antiplasmin, to be responsible for the coagulopathy. Alpha-2-antiplasmin deficiency may well contribute to the bleeding disorder in acute promyelocytic leukemia.

Antithrombin III↗
PubMed1985

Impairment of cellular immunity and OKT4 lymphocytes in symptom-free hemophiliacs with antibodies to human T leukemia virus III (HTLV III).

Antibodies against the human T-leukemia virus III (HTLV III) were detected by immunofluorescence in the sera of 17 out of 48 hemophiliacs (35.4%) without AIDS or ARC, frozen in 1983-84. Immunological data collected at that time were re-evaluated by separating HTLV III-positive and negative subjects. HTLV III positive patients had significantly reduced OKT4 cells (both in %: 26.1 +/- 10.9 vs 41.2 +/- 15.2; P less than 0.01; and in absolute numbers: 469 +/- 291 vs 1,038 +/- 541; P less than 0.005) and OKT3 lymphocytes (in absolute numbers: 1,234 +/- 550 vs 2,050 +/- 1,067; P less than 0.01). Subpopulations identified by other monoclonal reagents (OKT8, Leu 7, OKM1, anti-Tac) showed no significant differences between the two groups. Patients subsequently found to be seropositive had significantly more frequent anergy to skin tests to recall antigens and often an impairment of in vitro response to phytohemagglutinin A. Despite these relevant defects of some tests of cell-mediated immunity, in HTLV III-positive cases no clinical progression toward AIDS-related complex was observed in a mean period of follow-up of more than 1.5 years.

Acquired Immunodeficiency Syndrome↗