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C Tarella

Publications and source records attributed to C Tarella.

At least 73 records · Page 4Linked to original sources
PubMed1989

MACOP-B treatment for advanced stage diffuse large cell lymphoma: a multicenter Italian Study.

Seventy-one patients with advanced stage diffuse large cell lymphoma were treated with MACOP-B. Sixty-nine per cent of patients achieved a complete response (CR), 10% a partial remission, while 11% had no response and 10% died because of toxicity. The CR rate was adversely affected by immunoblastic type, poor performance status and bone marrow involvement. Two-year survival for all 71 patients was 55% and 2-year disease-free survival (DFS) for the 49 CRs was 73%. Relapses were lower (P less than 0.05) in patients achieving CR in 8 weeks or less (DFS 83% vs. 59%) and in patients without tumor bulk (DFS 87% vs. 54%). Overall toxicity was acceptable with mucositis proving to be the most frequent severe side-effect. However, treatment-related deaths were unacceptably high in patients over 59 years of age (30% vs. 7%). Thus for the elderly MACOP-B is potentially lethal and must be used cautiously. These preliminary results confirm the effectiveness of MACOP-B. The delay of response and/or the presence of tumor bulk may be important prognostic factors in identifying a subset of poor risk patients with a high incidence of relapse.

Adolescent↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor requires interaction with accessory cells or granulocyte-colony stimulating factor for full stimulation of human myeloid progenitors.

Human recombinant GM-CSF (rGM-CSF) was tested on highly purified and fractionated CFU-GM subsets. The fractionation was performed with the DS1-1 monoclonal antibody (MoAb), which distinguishes early and late CFU-GM. On whole bone marrow cells, rGM-CSF had a colony-stimulating activity comparable to that of known sources of CSFs, ie, the supernatant (SN) of TPA 30-1 or 5637 cell lines, used as control. A greatly reduced activity was observed when CFU-GM were depleted of phagocytizing and E rosetting cells (colony growth of 27% as compared with control). On fractionated CFU-GM, the rGM-CSF activity was even more reduced on both early and late progenitors (18% and 6% of colony growth, respectively). However, when rGM-CSF was used together with rG-CSF at suboptimal concentrations, the colony growth reached values analogous to that of control cultures. A synergistic interaction between rGM-CSF and rG-CSF in stimulating either early or late myeloid progenitors was observed. The results suggest that the activity of rGM-CSF on CFU-GM is mainly exerted through cooperation with accessory cells. r-G-CSF is one of the factors that can synergistically cooperate with r-GM-CSF in the myelopoietic stimulation.

Bone Marrow↗
PubMed1989

Monoclonal antibody purging and autologous bone marrow transplantation in acute myelogenous leukemia in complete remission.

A mouse monoclonal antibody (S4-7) reacting with human myelomonocytic cells has been previously shown to be suitable for bone marrow purging in selected acute myelogenous leukemia (AML) patients with S4-7 positive leukemic clonogenic cells at diagnosis. The results obtained in seven AML patients who underwent such a treatment, followed by autologous bone marrow transplantation (ABMT), are now reported. Six patients underwent ABMT in first complete remission (CR), one in second CR, after BAVC conditioning regimen. One patient died of infection 1 month after ABMT; in the other six a complete recovery of hemopoiesis was observed. In spite of S4-7 reactivity with normal myelomonocytic cells, a prompt recovery of granulopoiesis was however observed both in in vitro liquid culture and in vivo with a median time of 20 days to reach granulocyte values of 500 x 10(6)/l. The patient transplanted in 2nd CR relapsed 3 months after ABMT. Of the five evaluable patients transplanted in 1st CR, two relapsed 8 and 9 months post-ABMT while three remain in continuous CR at 35, 47, 57 months. Leukemic cells of two of the three patients with recurrent disease were studied at relapse and in both could be detected a significant percentage of S4-7 negative cells, detectable neither at diagnosis nor (one patient) at the time of first relapse after standard chemotherapy.

Antibodies, Monoclonal↗
PubMed1988

Immunological separation of two CFU-GM subsets showing different responsiveness to T-cell derived growth factors.

Among human myeloid precursors two different subpopulations can be distinguished: type-2 CFU-GM, more differentiated, reacting to the monoclonal antibody DSl-1 and type-1 CFU-GM, more immature, negative to the DSl-1. Using this monoclonal antibody, type-1 and type-2 CFU-GM were fractionated and separately grown in the presence of T-cell derived CSFs, i.e., conditioned medium of PHA-stimulated T-lymphocytes (PHA-Ly) and the supernatant of Il-2-dependent normal T-cell lines (TC-SN). The supernatants of two neoplastic non-T cell lines, TPA-30-1 and GCT, were used as control. PHA-Ly and TC-SN had a very weak activity on type-2 CFU-GM (18 and 14% of colony growth, compared to control). However, they potently stimulated type-1 CFU-GM (84 and 68.5% of colony growth, compared to control). The restricted activity of T-cell derived CSFs on early myeloid progenitors is therefore demonstrated. Our results also show that CFU-GM with different responsiveness to growth factors can be physically separated on the basis of their reactivity to monoclonal antibody DSl-1.

Antibodies, Monoclonal↗
PubMed1987

Trophoblast cell line conditioned medium for in vitro culture and antigenic characterization of acute myeloid leukemia clonogenic cells.

The colony-stimulating factor-containing supernatant of the human trophoblast cell line TPA-30-1 was used to stimulate in vitro growth of acute myeloid leukemia clonogenic cells from 54 patients. Prevalent colony growth (10-greater than 1000) was observed in 63% of cases. In 31% clusters and a few colonies (1-9/1 x 10(5) plated cells) were scored. Neither colonies nor clusters could be detected in the remaining 6%. The best growth was observed in subtype M5 (8 of 9 cases, 89%). Morphological examination and recloning tests suggested that the colonies originated from leukemic progenitors. TPA-30-1 supernatant stimulation can therefore be compared with that of phytohemagglutinin or phytohemagglutinin-leukocyte-conditioned medium. In addition it does not require T-lymphocyte removal and batch screening. Extension of the culture for antigenic characterization of acute myeloid leukemia clonogenic cells to more patients than in a previous study confirmed the existence of a subgroup (39%) of patients whose acute myeloid leukemia clonogenic cells constantly expressed late myeloid differentiation antigens recognized by the monoclonal antibody S4-7. Since S4-7 spares early normal hemopoietic progenitors, this subgroup (54% M2) can be considered as candidates for autologous bone marrow transplantation after in vitro purging with S4-7 monoclonal antibody and complement.

Antigens, Neoplasm↗
PubMed1987

Autologous bone marrow transplantation in acute myeloid leukemia after in-vitro purging with an anti-lacto-N-fucopentaose III antibody and rabbit complement.

Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfusion of S4-7 purged cells, regeneration of marrow cells occurred with prompt recovery of granulopoiesis and erythropoiesis. A more delayed platelet recovery was observed. The two patients are in complete remission at 20 and 11 months from ABMT. The results indicate that immunologic purging with S4-7 MoAb is safe and suitable for selected AML patients undergoing ABMT.

Adolescent↗
PubMed1986

Antigenic phenotype of myelomonocytic progenitors (CFU-GM) in chronic myeloproliferative disorders.

The antigenic phenotype of myelomonocytic progenitors [colony-forming unit granulocyte-macrophage (CFU-GM)] from 33 patients with chronic myeloproliferative disorders was investigated using four cytotoxic monoclonal antibodies. Monoclonal antibodies S3-13, S8-6, and S16-144 which recognize normal hemopoietic progenitors of different lineages reacted with almost all CFU-GM. R1B-19 monoclonal antibody identified two subpopulations of myelomonocytic progenitors (type 1 and 2 CFU-GM), as reported previously in normal subjects. In 3 of 11 patients with chronic myelogenous leukemia, in 1 of 2 patients with chronic myelomonocytic leukemia, and in 2 of 4 patients with polycythemia vera, a higher proportion of the more immature CFU-GM (type 1) was detected in bone marrow cells. The more differentiated CFU-GM (type 2) is not detectable in normal peripheral blood. By contrast, in 14 of 15 chronic myelogenous leukemia patients, in 1 of 2 chronic myelomonocytic leukemia patients and in 3 of 8 patients with idiopathic myelofibrosis, it was present in high to very high proportions. It is clear from these findings that the antigens present on normal CFU-GM are expressed in chronic myeloproliferative disorders. The proportion and distribution of type 1 and 2 CFU-GM, on the other hand, are very different from those observed in the normal subjects.

Adult↗
PubMed1985

Release of hemopoietic factors by normal human T cell lines with either suppressor or helper activity.

We analyzed the release of activities capable of stimulating the in vitro growth of human hemopoietic progenitor cells by long-term cultured T cell growth factor (TCGF)-dependent human T lymphocytes. Seven cell lines tested produced colony-stimulating activity (CSA) as well as burst-promoting activity (BPA). The CSA stimulated primarily the growth of the cells forming colonies after 14 days of incubation. In addition the supernatants from these seven T-cell lines showed the ability to induce the in vitro growth of mixed granulocyte, erythroid, megakaryocyte, macrophage colonies (CFU-GEMM). The release of hemopoietic factors did not depend on the presence of accessory cells or phytohemagglutinin or serum during the incubation for factor production. In six of the T cell lines the majority of the cells were reactive to the OKT 8 monoclonal antibody (MoAb), whereas one cell line contained mostly OKT 4+ cells. Suppressor activity was detected in three tested OKT 8+ cell lines, while the one OKT 4+ displayed helper activity. All cell lines produced hemopoietic factors with equal efficiency. These results indicate that factors affecting human hematopoiesis are produced by normal T lymphocytes in long-term culture and this property is not related to the helper or suppressor activity of the cultured cells.

Adult↗
PubMed1983

Functional and phenotypic characterization of two HL60 clones resistant to dimethylsulfoxide.

Two HL60 clones (C12 and C13) totally insensitive to differentiation induction by dimethylsulfoxide (Me2SO) are described. They have been growing continuously in the presence of the inducer for more than 6 months. The morphological and cytochemical features of the two populations are quite similar to those of the original HL60 cell line, whereas a different karyotype with marked hyperploidy (modal chromosome number of 86 for C12 and 82 for C13) was detected. An antigenic pattern analogous to that of the native HL60 cell line was found in C12 and C13 populations using three monoclonal antibodies differently reactive to myeloid cells. Both clones can be induced to differentiate by retinoic acid (RA) and 12-O-tetradecanoylphorbol 13-acetate (TPA). The pattern of differentiation was assessed by morphological, cytochemical, phenotypical and functional markers. Differentiation of C12 cells by RA and TPA was similar to that observed with native HL60 cells, whereas C13 cells showed lower degrees of sensitivity to RA and TPA. The data presented suggest the existence of different mechanisms for induction of differentiation by Me2SO, RA and TPA. In addition, they are in accordance with previous observations of different degrees of inducibility to differentiation among leukemic cell populations in culture.

Cell Differentiation↗
PubMed1982

Induction of differentiation of HL-60 cells by dimethyl sulfoxide: evidence for a stochastic model not linked to the cell division cycle.

Induction of differentiation of human promyelocytic leukemia cell line HL-60 by dimethyl sulfoxide (Me2SO) was analyzed to determine the relationship between exposure time of the inducer and cell cycle. A minimum incubation time of 12 hr with Me2SO was required in order to induce differentiation in a small but significant proportion of cells. These expressed differentiation markers (morphology, phagocytosis, and nitroblue tetrazolium reduction) up to 12 hr after Me2SO was removed from the medium. For periods beyond 12 hr and as long as 120 hr of contact of HL-60 cells with the inducing agent, a linear rise in the percentage of differentiated cells was observed. The sensitivity to Me2SO of HL-60 cells synchronized by double thymidine block was examined and was found to be similar to that of nonsynchronized cells. The effect of Me2SO was not altered when incubated with cells at different phases of the cell cycle. Finally, even nonproliferating cells were sensitive to the inducing effect of Me2SO. The data are consistent with a stochastic model of induction to differentiation without having any linkage to the cell cycle.

Cell Cycle↗
PubMed1982

Terminal differentiation of the human promyelocytic leukemia cell line, HL-60, in the absence of cell proliferation.

Induction of differentiation of the human promyelocytic leukemia cell line, HL-60, by dimethyl sulfoxide was analyzed for a requirement for cell replication. The ability of HL-60 cells to undergo terminal granulocytic differentiation as judged by nitroblue tetrazolium reduction, phagocytosis, and morphological criteria was not impaired by a total block in cellular proliferation. Retinoic acid, actinomycin D, and butyric acid also induced differentiation of HL-60 cells in the absence of cell growth. These results and the earlier demonstration that phorbol ester-induced macrophage differentiation of HL-60 occurred independently of DNA synthesis indicate that in these leukemic cells there is a dissociation of proliferation and maturation. The ability of retinoic acid to enhance differentiation of HL-60 cells was not altered in the presence of various growth-inhibiting concentrations of two clinically useful chemotherapeutic agents: hydroxyurea and 1-beta-D-arabinofuranosylcytosine. These results suggest that combination therapy in a program aimed at both inhibiting proliferation and inducing differentiation of leukemia cells could be beneficial.

Cell Cycle↗
PubMed1982

Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells.

Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst-promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis.

Cell Line↗
PubMed1979

The importance of the genetic picture and globin synthesis in determining the clinical and haematological features of thalassaemia intermedia.

Twelve carriers of thalassaemia intermedia were studied. Their clinical and haematological picture was distinctly different from that in both heterozygotes and homozygotes for beta thalassaemia. Several genetic patterns were found responsible for thalassaemia intermedia: beta/delta beta thalassaemia, alpha 2 beta/beta thalassaemia-heterocellular HPFH. In a few subjects the genetic picture indicated that the patients were homozygous for beta thalassaemia, in spite of the mildness of the clinical situation. The lack of genetic uniformity was refelcted in very wide Hb A2 (2.5--8.7%) and Hb F (7.5--96.9%) ranges, as opposed to the noticeable degree of biochemical uniformity indicated by the very similar imbalance of globin chain synthesis: 0.33-0.54 for the non-alpha/alpha chain ratio in the peripheral blood. The mean for this parameter (0.43 +/- 0.05) was significantly different (P less than 0.001) from that observed in heterozygous carriers (0.60 +/- 0.10) and homozygous carriers (0.11 +/- 0.05) for beta thalassaemia. The marrow blood displayed a comparable pattern. It is therefore suggested that the severity of thalassaemia is attributable to the degree of chain synthesis imbalance.

Adolescent↗
PubMedDate not supplied

Stage II large B-cell lymphoma with sclerosis treated with MACOP-B.

In a series of 193 patients with advanced stage diffuse large-cell lymphoma (DLCL) treated with MACOP-B, 18 (11%) were defined as having a stage II large B-cell lymphoma with sclerosis of the mediastinum. This type of lymphoma has been reported to have a highly aggressive behaviour and special histological and clinical features. In our series young women were more commonly affected and the most striking clinical feature was the presence of a bulky mediastinal mass in 81%. A comparison was made between stage II patients with DLCL with and without sclerosis. The group of patients with sclerosis had prognostic parameters significantly worse than those of the patients without sclerosis, namely, elevated LDH level and bulky disease. The complete remission rates (89% vs 76%) were similar in the two groups and, with a median follow-up of 23 months, survival and disease-free survival rates were also superimposable. MACOP-B chemotherapy has been proven effective in this subgroup of lymphoma patients with sclerosis that had thus far been reported to have a poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

MACOP-B treatment for intermediate and high-grade non-Hodgkin's lymphomas at diagnosis and in relapse.

Between October, 1984 and October, 1987 a study program was carried out to evaluate the efficacy of MACOP-B in the advanced stages of intermediate/high-grade malignancy non-Hodgkin's lymphomas (NHL). Thirty patients were treated at diagnosis: 14 with D-E-F histology (median age = 56.5 years) and 16 with G-H histology (median age = 46.5). Complete remission (CR) rate was 42.8% for the D-E-F subgroup and 81.2% for the G-H subgroup. Bone marrow involvement was the major adverse factor for CR achievement in patients with intermediate-grade NHL. Overall, disease stage, bulky presentation and the presence of systemic symptoms did not significantly affect response to therapy. Survival curves predict 73% of patients alive at 45 months (median follow-up = 30 mo.). No significant differences were seen between D-E-F (64%; median follow-up = 36 mo.) and the G-H patients (81%; median follow-up = 27 mo.). The disease-free survival curve for all patients in CR reached a plateau phase at 78% (median follow-up = 30 mo). MACOP-B was much less effective when employed in 10 patients at relapse; only 2 out of these 10 reached a durable CR, which persisted 51 and 27 mo. after MACOP-B. The remaining 8 patients had a partial response, followed closely by disease progression: 7 died, whereas 1 patient is still alive after salvage therapy with bone marrow transplant. Thus, MACOP-B proved to be effective in patients at diagnosis with G-H histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

GM-CSF-exposed peripheral blood progenitors as sole source of stem cells for autologous transplantation in two patients with multiple myeloma.

Two patients (aged 52 and 44) received high-dose sequential chemotherapy followed by myeloablative therapy and autotransplantation as first line treatment of a stage III multiple myeloma with high plasmacell labelling index. Autograft was performed with peripheral blood cells collected after high-dose etoposide followed by rhGM-CSF continuous infusion. During this period very high numbers of circulating hemopoietic progenitors were detected in both patients. Prompt, complete and durable hematological recovery was observed after autograft with peripheral blood stem cells. Thus, we conclude that massively released progenitors after high-dose chemotherapy and rhGM-CSF include stem cells capable of marrow reconstitution.

Adult↗
PubMedDate not supplied

Use of peripheral blood stem cells to accelerate hemopoietic recovery following autologous bone marrow transplantation.

Twenty-one patients with high risk non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) underwent autologous bone marrow transplantation (ABMT). Nine out of 21 patients received in addition to bone marrow (BM) cells also peripheral blood (PB) cells collected by leucapheresis performed in the recovery phase after high-doses of either cyclophosphamide or etoposide (7 patients), or after ara-C (2 patient). All patients receiving BM + PB cells had ABMT as salvage therapy following extensive relapse or progression of their disease. The addition of PB cells to BM cells allowed a significantly faster recovery after ABMT. Median time to reach WBC greater than 1,000/microL was 14 days versus 20.5 days for patients receiving BM only. Furthermore, a reduced requirement of supportive care and a shorter period of isolation was observed. These results confirm that PB cells combined with BM cells allow a prompt hematopoietic reconstitution after myeloablation. In addition, the data demonstrate the efficacy of PB cells collected after various cytotoxic drugs, even in patients previously exposed to cytoreductive regimens.

Adolescent↗