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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 397 records · Page 22Linked to original sources

Lymphocyte subpopulations and cell mediated cytotoxicity in acute non-lymphoid leukemia (ANLL) patients in complete remission (CR) and off-therapy.

An assessment of the lymphocyte sub-populations and cell mediated cytotoxicity was made in 12 adults with acute non-lymphoid leukemia after stopping chemotherapy. No significant differences were found between ANLL and controls, for absolute lymphocyte count, %SIg/+ cells, Fc gamma + cells and ERFC. The OKT4+/OKT8+ was reduced in ANLL. Leu-7+ cells were significantly higher in ANLL. Moreover it appears that in ANLL lymphocyte function is restored early after stopping chemotherapy.

Acute Disease↗

Peripheral T cell lymphoma in adults: morphological and phenotypical study of four cases.

In the present study we investigated the lymph node morphology and distribution of cell surface phenotypes in four cases of adult peripheral T cell lymphoma. Histologically, the tumors were classified as T zone lymphoma, T cell lymphoma with large multilobated nuclei and T cell immunoblastic sarcoma. In the T zone lymphoma the neoplastic lymphocytes were E+ (90%) and exhibited intensive focal staining for acid phosphatase (93%) and acid esterase (92%); the phenotype distribution revealed low expression of the T-3 antigen (49%), selective expression of the T-4 antigen (72%) and poor expression of T-6 (10%) and T-10 antigens (22%). Some of these features are present in normal and in neoplastic immature T cells. In the remaining three cases the majority of lymph node cells were E+ (59-75%), T-3+ (67-80%) and T-8+ (43-55%). A distinctive feature of the T cell immunoblastic sarcoma was the presence of high percentages of DR+ cells (62%; 63%). Thus our results indicate that the morphological heterogeneity of peripheral T cell lymphoma is also paralleled by a variety of surface phenotypes and that phenotype studies may provide a useful contribution to identification and accurate classification of peripheral T cell neoplasms.

Adult↗

Chemotherapy in hairy cell leukemia. Preliminary results of a nonaggressive regimen.

Three patients with hairy cell leukemia, only one splenectomized, were treated with a combination of vinblastine plus bleomycin at low doses. One achieved a complete remission and another achieved a good partial hematologic and bone marrow remission. Neither of them has relapsed after follow-up periods of 34 and 17 months, respectively. The third patient, although achieving a hematologic improvement, died because of a cytomegalovirus pneumonitis after 2 cycles of chemotherapy. Chemotherapy is not usually employed in the initial management of hairy cell leukemia. However, if life-threatening neutropenia and thrombocytopenia occur secondary to severe bone marrow leukemia infiltration and an improvement does not take place using alternative therapeutic strategies, chemotherapy should be taken into consideration. The nonaggressive chemotherapeutic regimen the authors propose induces a cytoreduction without an evident myelosuppression, and can be also employed on an outpatient basis.

Adult↗

S-100+ lymph node neoplasm. Report of a case with histological AL and immunological features intermediate between T cell lymphoma and malignant histiocytosis.

A 16-yr-old white female was affected by continuous fever, pancytopenia with relative increase of T-8 lymphocytes, severe bone marrow hypoplasia, generalized lymphadenomegaly and splenomegaly. A first lymph node biopsy, obtained at the onset of the disease, was involved by a paracortical tumor with some S-100+ "lymphocyte-like" cells in the neoplastic areas; in the cell suspension, 70-80% of cells were E4+/E37+ lymphocytes with prevalent expression of the T-8 phenotype (52%). A second lymph node biopsy, obtained five months later, was involved by a diffuse proliferation of S-100+ cells with high mitotic activity; in the cell suspension, the majority of cells were E-/T-11+/T-3+/T-8+. At the TEM level, the neoplastic cells were characterized by regular or indented nuclei with finely dispersed chromatin and by regular or indented nuclei with finely dispersed chromatin and by irregular cytoplasmic profiles with thick pseudopodia-like projections. The possibility is discussed that this neoplasm may share some similarities with the T-gamma lymphoma being part of a poorly described group of tumors with intermediate features between T cell lymphoma and malignant histiocytosis.

Adolescent↗

Classification of patients with T-cell chronic lymphocytic leukemia and expansions of granular lymphocytes: heterogeneity of Italian cases by a multiparameter analysis.

The peripheral blood mononuclear cells (PBMC) from 750 Italian patients with chronic lymphocytic leukemia (CLL) were evaluated in order to detect cases with T-cell expansions. The PBMC of 18 patients (2.4%) were found to be capable of rosetting with sheep red blood cells. Further characterization of these cells with a panel of monoclonal antibodies and other immunological and cytochemical tests led us to tentatively subdivide these 18 patients into three groups. The first one included 6 patients whose cells expressed a T-helper phenotype: they exhibited frequent skin involvement and an aggressive clinical course, and some of the patients in this group demonstrated chromosome abnormalities. On the other hand, group 2 (10 cases with expansions of granular lymphocytes and/or T suppressor-bearing phenotype cells) usually presented with a mild clinical course. These cases did not generally require therapy and a diagnosis of leukemia could not be unequivocally confirmed. Cells from the two remaining patients displayed both B-cell markers and E-rosetting ability, thus belonging to the rare group of false T-cell CLL. In fact, the clinical course and management of the latter cases were similar to those of classical B-CLL disease. In the first and second groups, mechanisms reported to be involved in mature T-cell proliferations (response to interleukin-2, production of interleukin-2 or interferon) were investigated, but the cells under study displayed neither growth ability nor lymphokine production in the above assays. In addition, these cells were negative with the anti-Tac monoclonal antibody that appears to recognize the receptor for interleukin-2. More importantly, none of these patients had serum antibodies to the recently described human T-cell leukemia/lymphoma virus (HTLV), possibly responsible for Japanese and West Indian adult T-cell leukemia (ATL) and for sporadic cases of ATL observed in other countries. Taken together, our results outline some differences between European and ATL patients. Furthermore, the data presented point out the heterogeneity of the disease and emphasize that an immunological classification and, in particular, the detection of a helper phenotype have relevant prognostic and therapeutical importance.

Adult↗

Sequential combination of high dose ARA-C (HiDAC) and asparaginase (ASP) for the treatment of advanced acute leukemia and lymphoma.

Thirty patients with advanced acute leukemia and lymphoma were treated with the sequential combination of high dose ARA-C (HiDAC 3 gm/m2 infused i.v. over 3 h at 0, 12, 24, 36 h) and asparaginase (ASP 6.000 IU/m2 i.m. at hour 42). The sequence was given on day 1 and 8 irrespective of the degree of myelosuppression. Of 22 patients with leukemia there was only one who was absolutely refractory to therapy. Complete remission was induced in 3 patients with ANLL (30%) and in 3 with ALL (30%). Three patients became hypoplastic but recovered with blasts and 12 died from infection, complicated by intracranial hemorrhage in 3, during hypoplasia. Of 8 patients with lymphoma, 2 were clearly refractory to therapy, one died from sepsis and the remaining 5 all entered remission (2 CR + 3 PR, 62%). Activity of HiDAC/ASP against CNS disease is suggested by the clinical response seen in patients with overt meningeal or intracerebral involvement. Toxicity associated with HiDAC/ASP was mainly hematologic. All but one patient experienced hypoplasia and severe pancytopenia; documented infections and major hemorrhages occurred in 80 and 20% of patients respectively. We conclude that HiDAC/ASP is a regimen with definite activity against acute leukemia and lymphoma including CNS disease. Alternate treatment schedules should be explored in order to reduce marrow toxicity.

Adolescent↗

PHA-ICC, ADCC and NK in patients with ANLL in CR: human fibroblastic interferon fails to increase NK-active cell frequency.

PHA-ICC, ADCC and NK activity of PBL were studied in ten patients with ANLL in CR and in eighteen normal controls in the presence and absence of HFIF. No statistically significant differences were recorded among the two groups with regard to basic lymphocyte functions. Although the parameters of lymphocyte function remained analogous for those tested, the analysis at the single cell level revealed that HFIF stimulation increases the number of NK active cells and target binding cells among normals, but not in leukemic patients.

Adult↗

Evaluation of the effectiveness of DDAVP in surgery and in bleeding episodes in haemophilia and von Willebrand's disease. A study on 43 patients.

1-deamino-8-D-arginine-vasopressin (DDAVP), was used in a wide spectrum of clinical situations employing two different dosages (0.3 and 0.4 microgram/kg b.w.) for the management of 43 patients with factor VIII deficiencies--mild and moderate haemophilia A and von Willebrand's disease (vWD). In most instances, the drug was given in association with antifibrinolytics. Twenty-five dental extractions were carried out with two different protocols: one based upon a single infusion and the other based upon three infusions. Bleeding occurred in three patients regardless of the protocol used. The vasopressin analogue promptly stopped bleeding in 12 'spontaneous' open bleeds (haematuria, epistaxis, menometrorrhagia, gum bleeding) and it appears to be also effective in closed bleeds. DDAVP was used to minimize blood loss during surgical interventions and to avoid haemorrhage in the postoperative period. Nine surgical procedures were carried out in six vWD patients and three haemophiliacs. Bleeding occurred late in the postoperative period on one occasion only. No difference was demonstrated between the two doses of the drug either in terms of clinical benefit or rise of factor VIII coagulant activity. The efficacy of DDAVP and the absence of side-effects make this vasopressin analogue worthy of consideration as a reliable alternative to factor VIII concentrates in a wide variety of clinical situations.

Antigens↗

Cytogenetic findings in acute promyelocytic leukaemia. A report of 25 cases.

Cytogenetic analyses of bone marrow cells were carried out by means of direct technique and short-term cultures in 25 acute promyelocytic leukaemia (APL) patients. 16 were affected by the hypergranular form and 9 by the M3-variant. The t(15;17) was documented at diagnosis in 15 patients. In addition, 2 cases, in which an M3 morphology and a normal karyotype on direct preparation were found at diagnosis, disclosed the chromosome anomaly in cultured cells at relapse, in concomitance with a change of blast morphology to the M3-variant. However, the t(15;17) was a consistent feature in 5 of the 15 patients with cells analysed on direct preparations only and in all cases who had successful bone marrow cultures. Overall, the 15;17 translocation was detected in 7 out of 9 patients with the M3-variant and in 8 out of 16 patients with typical M3. Whenever the chromosome preparations were made after culture, 7/7 had the translocation in the M3-V group and 5/5 in the M3 group. No obvious differences in clinical features or outcome were evident in the patients, irrespective of their cytogenetic findings.

Adolescent↗

A study of the mechanisms and sites of action of desferrioxamine in thalassaemia major.

The effects of slow subcutaneous (s.c.) infusions of desferrioxamine (Desferal: DF) on iron metabolism and excretion were studied in 6 thalassaemia major patients in the course of a ferrokinetic study with 59Fe as a label; s.c. DF infusions were performed every 4th day starting 4 days after that of the 59Fe injection. Serum iron and total iron binding capacity (TIBC) increased after s.c. infusion, whereas serum ferritin levels remained unchanged. 59Fe urinary specific activity decreased in all subjects from the first to subsequent infusions, whereas faecal specific activity remained almost constant throughout the experiment. These data support the hypothesis that iron reaching RE cells concentrates initially in a readily chelatable pool from which then it moves to a larger and not readily chelatable pool, whereas iron reaching parenchymal hepatic cells remains permanently available to chelant.

Child↗

Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.

Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.

Adult↗

2-Methyl-9-hydroxyellipticinium acetate (ellipticinium) in the treatment of lymphomas. Preliminary results of a phase II study.

Eighteen patients with advanced refractory lymphomas were treated with 2-methyl-hydroxyellipticinium (ellipticinium); there were 14 non-Hodgkin's (NHL) and 4 Hodgkin's lymphomas (HL). Ellipticinium was administered at the dose of 100 mg/m2 daily for 3 days i.v. with courses repeated at 3 week intervals. Preliminary results indicate some antitumor activity of the drug against NHL with minimal toxicity. Of the 16 evaluable patients 1 partial remission and 7 minor responses were noted among the NHL (65%). Myelosuppression was minimal and clinical toxicity was mild. Further evaluation of this drug in untreated patients appears to be warranted.

Adult↗

Characterization and treatment of the non-lymphoblastic crisis of chronic myelogenous leukemia.

Fifty-six consecutive patients affected by the non-lymphoblastic-like crisis of chronic myelogenous leukemia were the subjects of this study. The cytologic and cytochemical features, together with the extension of clinical involvement, were investigated in all the patients. The most frequent cytologic variant was the "myeloid" one (60% of the patients). All the patients received a standard treatment (hydroxyurea, 6-mercaptopurine +/- prednisone). The overall median survival was 5.1 months; however, 22% of the patients survived for one year or more. The length of survival was independent of the cytologic variety and clinical conditions (previous splenectomy, organomegalies, etc.). There was no correlation between drug dosage and length of survival, whereas the disappearance of blast cells from the peripheral blood appeared to be directly correlated with a longer survival. The treatment was well tolerated (slight hematologic and hepatic toxicity) and allowed a reasonably good quality of life: most of the patients were treated on an out-patient basis.

Adolescent↗

MOPP treatment of resistant Hodgkin's disease following ABVD failure.

Fourteen patients with Hodgkin's disease resistant to ABVD were treated with MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone). Complete remission was obtained in 6 patients (43%). Four of the 6 complete responders are disease free after 5, 20, 23, 35 months. The actuarial median survival after MOPP of all patients is 20 months. These data confirm that there is no "cross-resistance" among the drugs included in the two schedules.

Adolescent↗

Long-term survival in adolescent and adult acute lymphoblastic leukemia.

Among 164 patients with acute lymphoblastic leukemia (ALL) (age greater than 11 years) induced into complete remission at four hospitals in Italy and The Netherlands between 1971-1977, 49 survived for more than three years in continuous complete remission. Features at diagnosis of the 49 long-term survivors were compared with those of the parent group. The long-term survivors presented with significantly lower leukocyte counts and were slightly younger. Late relapses occurred in nine patients after 37-91 months from remission. Of the 45 patients who had all treatment stopped after 24-60 months of continuous remission, seven have relapsed. Relapses, mainly in the marrow, occurred 4-32 months after cessation of therapy, the risk of relapse being greatest in the first year and dropping to zero by the fourth year. ALL appears curable in approximately one fifth of adolescents and adults entering complete remission with adequate chemotherapy.

Adolescent↗

E-rosette positive acute lymphoblastic leukaemia in adolescents and adults.

E-rosetting of leukaemic blast cells is one of the markers of T-cell acute lymphoblastic leukaemia (ALL). In children, E+ ALL has a bad prognosis. In adults, data are scarce. This report provides information on 25 E+ ALL adult patients who have a minimum follow-up time of 36 months. Twenty-two of 25 patients (88%) achieved complete remission (CR) (median duration 16 months), and six of them were alive, relapse-free, and off therapy after 36-81 months, with a 26% projected 6-year relapse-free survival. In 97 patients with E-SmIg- ALL, who were treated at the same Institutions, over the same period of time, and by the same modalities, the outcome of therapy was almost identical: CR 80%, median duration of first CR 15 months, projected 6-year relapse-free survival 15%. The white blood cell (WBC) count at presentation influenced significantly and to the same degree first CR length in both E+ and E- cases. In this adult series, WBC count was not as high as in children. Moreover, a high Hb concentration, a very high WBC count, lymphadenomegaly, and mediastinal involvement, were found more frequently in adolescents and young adults than in adults. Based on these data, it is suggested that in adults E-rosetting as such is not a marker of a poorer prognosis, that some of the typical features of children E+ ALL weaken with age, and that in adults the disease can have a less aggressive character.

Adolescent↗