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Biomedical subjects

G Piaggio

Publications and source records attributed to G Piaggio.

At least 127 records · Page 7Linked to original sources
PubMed1984

Treatment of severe aplastic anemia with high-dose methylprednisolone and antilymphocyte globulin.

Fifty patients with severe aplastic anemia (SAA) were treated with immunosuppressive regimens consisting of high-dose 6-methylprednisolone (HD-6MPr) followed by or given in combination with anti-lymphocyte globulin (ALG). Eighteen of 50 patients given one course of immunosuppression (IS) showed a response, as defined by self-sustaining peripheral blood counts, with no further need for transfusions; 8 of 27 and 2 of 7 patients given, respectively, two or three courses of IS responded. The overall response rate was 28 of 50 (56%). Seventeen patients died, 5 are alive but pancytopenic. The actuarial six-year survival is currently 65%. The following prognostic factors on admission were significantly associated with response to IS: 1) age over 30 years (P = .005), 2) a short interval from diagnosis to treatment (P = .03), 3) a small number of transfusions before treatment (P = .004). The sex of the patient, the number of transfusions before treatment, and the number of CFU-c from unfractionated as well as from T-depleted bone marrow had no significant influence on response to IS. After one month from IS, however, patients responding to IS had a significantly (P = .01) higher number of CFU-c on T-depleted marrow cells, compared with nonresponders. The present study confirms that over 50% of patients with SAA can be successfully treated with IS. Older patients, with a short interval from diagnosis to treatment and with rapid recovery of CFU-c growth on T-depleted marrow, have the best chance for autologous hematopoietic reconstitution.

Adolescent↗
PubMed1983

Generation of CFU-c suppressor T cells. VI. Effect of cyclosporin A.

CFU-c suppressor T cells were generated in vitro by culturing overnight peripheral blood T cells from healthy donors with pokeweed mitogen (PWM), or T cells from patients with severe aplastic anemia (SAA) in remission, with culture medium (RPMI). The supernatants were removed the next morning, the cells harvested and washed, and both tested for CFU-c suppression on normal marrow cells. Cyclosporin A (CyA) was added to this system to test whether it could abrogate or prevent the generation of suppressor cells. CyA was incubated with T cells, at a concentration of 0.1 microgram/ml, for 30 min at 37 degrees C and then washed away, in two different assays: (a) before T cells were incubated overnight in culture medium with or without PWM, or (b) after T cells had been kept overnight in culture. The results of this study indicate that CyA can prevent the generation of CFU-c suppressor T cells if preincubated with both normal or SAA T cells prior to in vitro priming, whereas it cannot abrogate the suppressor activity of primed T cells.

Anemia, Aplastic↗
PubMed1982

Generation of CFU-C suppressor T cells in vitro. V. A multistep process.

Different cell fractions obtained from five patients with immune severe aplastic anaemia (SAA) in complete autologous haematologic reconstitution were tested for CFT-c suppression. Bone marrow mononuclear cells (BMMC), but not peripheral blood mononuclear cells (PBMC), showed definite CFU-c inhibitory activity. On the contrary, both peripheral blood and marrow E rosetting cells (E+) suppressed CFU-c growth. The suppressor activity of PBE+ cells could not be rescued by adding back PBE- cells and/or PB adherent cells (AC). In addition, unfractionated PBMC exposed to sheep red blood cells (SRBC) suppressed CFU-c growth. PBMC from normal donors exposed to SRBC had no suppressor activity. This study suggests that CFU-c suppressor T cells in the peripheral blood of SAA patients are in different activation state as compared to BM cells from the same patients, and also differ from normal PB cells. The identification of T cells with different requirements for in vitro activation in order to exhibit a suppressor activity, suggests that generation of suppressor cells is a multistep process, and this may have practical implications for in vitro assays designed to test for immune suppression of haematopoiesis.

Anemia, Aplastic↗
PubMed1982

Generation of CFU-C suppressor T cells in vitro. III. Failure of mitogen-primed T cells from patients with chronic granulocytic leukemia to inhibit the growth of normal CFU-C.

T lymphocytes were derived by E rosetting from the peripheral blood (PB) and bone marrow (BM) of 15 patients with chronic granulocytic leukemia (CGL) in the chronic phase of their disease. T cells were also obtained from 12 healthy individuals. T cells were incubated overnight either in culture medium (RPMI) or RPMI plus pokeweed mitogen (PWM). The supernatants were then recovered and the cells washed in fresh RPMI. T cells from normal donors and from CGL patients were then cocultured with normal allogeneic marrow cells grown in soft agar for CFU-C colony formation. Target marrow cells were also grown in agar in the presence of T-derived supernatants. The results of this study can be summarized as follows. (1) Normal PB and BM T cells efficiently suppressed autologous and allogeneic CFU-C growth after PWM stimulation. (2) T cells derived from peripheral blood or marrow of CGL patients failed to inhibit CFU-C growth, whether pretreated with PWM or not. (3) The supernatants of PWM-treated normal T cells strongly inhibited CFU-C colony formation, whereas the supernatants of PWM-treated CGL T cells had no CFU-C/suppressor activity. These data indicate that T cells from CGL patients cannot be primed to become CFU-C suppressor cells after PWM: stimulation in vitro and cannot release a soluble inhibitor of granulopoiesis produced by PWM-primed normal T cells.

Adolescent↗
PubMed1982

Generation of CFU-c suppressor T cells in vitro. IV. effect of time on the inhibitory activity of mitogen-primed normal T lymphocytes.

Bone marrow and peripheral blood T cells were obtained from 15 normal individuals by E rosetting and cultured in round-bottomed microwells for 7 days in RPMI or in RPMI supplemented with mitogens (pokeweed mitogen, phytohemagglutinin or concanavalin A). Supernatants and cells were harvested on days 1, 2, 3, 4 and 7 and co-cultured with normal marrow cells in semi-solid agar to test their CFU-c suppressor activity. The results of this study indicate that (a) RPMI treated cells and their supernatants have no effect or an enhancing effect on CFU-c growth; (b) all 3 mitogens generate CFU-c suppressor T cells on day 1 of culture; (c) the inhibitory activity is detectable until day 4 of culture, though overall reduced, and is completely lost on day; 7 (d) the trend for supernatants of mitogen-treated T cells is quite similar with a tendency to complete loss of the inhibitory effect on day 7. We interpret these data as indicating that T cells release a soluble inhibitor of CFU-c growth within a few hours from polyclonal activation, the production of which is either controlled or lost with time in culture.

Anemia, Aplastic↗
PubMed1982

Generation of CFUC suppressor T cells in vitro. II. Effect of PHA, PWM, and Con-A on bone marrow and peripheral blood lymphocytes from healthy donors.

T lymphocytes were derived by E-rosetting techniques from the peripheral blood and bone marrow of 12 healthy donors. Following incubation of 18 h with PWM, PHA, Con-A or culture medium (RPMI) alone, the lymphocytes were harvested by centrifugation and washed. Both lymphocytes and culture supernatants were tested for CFUC suppressor activity in semisolid bone marrow cultures. The results of this study indicate that (a) T cells and supernatants from unstimulated cultures contained no CFUC suppressor activity, (b) T cells and supernatants from cultures stimulated with PHA, PWM or Con-A significantly suppressed autologous and allogeneic bone marrow CFUC, (c) there was no significant difference between the ability of bone marrow or peripheral blood T cells to inhibit CFUC, and (d) mitogens alone had either no effect or a moderate enhancing activity on marrow CFUC. These findings suggest that generation of CFUC suppressor T cells occurs normally within a few hours of polyclonal T cell stimulation.

Bone Marrow Cells↗
PubMed1981

Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure.

T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

Bone Marrow Cells↗
PubMed1980

T cell subpopulations after allogeneic bone marrow transplantation.

T-cell subpopulations were studied in six patients after allogeneic bone marrow transplantation for aplastic anemia and acute leukaemia, by means of receptors for IgG (TG-cells) and IgM (TM-cells). Significant modifications of TM-TG levels were found: a 2 to 10 fold increase of TG cells and a 2 to 10 fold decrease of TM cells from pre-transplant levels could be observed. The TM-TG imbalance appeared together with the clinical signs of GVHD: the level of TM-depression (but not the level of TG increase) correlated with the severity of GVHD. The TM-TG modifications were observed as long as 3 years after transplantation, also in the absence of signs of GVHD. In addition, all six patients were found to have severely impaired pokeweed-induced B-cell differentiation. The clinical implications and the possible lack of T-helper activity are discussed.

Acute Disease↗
PubMed1980

Lack of in vitro colony (CFUC) formation and myelosuppressive activity in patients with severe aplastic anemia after autologous hematologic reconstitution.

In vitro colony formation (CFUC) was studied in 8 patients with severe aplastic anemia (SAA) in complete hematologic remission following high dose pulse methylprednisolone (P/6-MPr) and/or antilymphocyte globulin (ALG). All patients except one were off maintenance treatment at the time of study, and follow-up ranged from 271 to 630 days. All patients showed marked reduction of colonies (2 +/- 3/2.5 x 10(5) cells; our normal 61 +/- 14) and clusters (77 +/- 45; our normal 179 +/- 83), which persisted for as long as 600 days after initial therapy. Incubation of patients' marrow with ALG did not enhance significantly colony formation. Co-culture of bone marrow from 6 patients with SAA in remission and normal marrow produced a marked inhibition of the expected colonies (84 +/- 16%) and clusters (29 +/- 23%). Incubation of patients' marrow with ALG prior to the co-culture experiments did not prevent suppression of colonies and clusters. Co-culture of patients' peripheral blood lymphocytes with normal marrow had no effect on colony formation. Therefore remission marrow from patients with SAA exhibits severely impaired in vitro growth (CFUC) and marked myelosuppressive activity against normal marrow cells. Incubation of patients' marrow with ALG has no significant effect on either assay.

Anemia, Aplastic↗
PubMed1979

Bone marrow transplantation for severe aplastic anemia. A report of 9 cases.

9 patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation (BMT). 5 were conditioned with cyclophosphamide and received and HLA-identical graft (4 patients) or a mismatched graft (1 patient): 1 rejected the graft on day 30 and died on day 34 during conditioning for a second transplant; 1 died on day 15 with acute and severe graft versus host disease (GvHD) in the absence of haemopoietic engraftment; 3 are alive and complete chimeras at 1,069, 490 and 332 days after transplantation. GvHD developed in 4 patients and was treated successfully in 3 with high dose methylprednisolone and/or antilymphocytic globulin (ALG). 4 patients were conditioned with ALG and received bone marrow from a haploidentical sibling or parent: 1 patient was refractory; 3 patients showed evidence of hematologic reconstitution, but 2 of these required a second course of ALG. 3 patients in this group are alive between 60 and 490 days; 1 patient died on day 121 of HBSAg-negative acute hepatitis.

Adolescent↗
PubMed1978

Lymphoid antigens on blast cells in the agranular metamorphosis of chronic myelogenous leukaemia.

Undifferentiated blasts from a Ph'-positive chronic myelogenous leukaemia (CML) in terminal metamorphosis were reacted in an indirect immunofluorescence test with antilymphocytic globulins (AHLGs), raised against cultured lymphoblasts, thoracic duct and peripheral blood lymphocytes from healthy donors. After proper myeloid and/or monocytic absorptions the AHLGs interacted strongly with the undifferentiated blasts of CML, while this was not true for parallel controls with non-lymphoid leukaemias, both acute and chronic. The intensity of fluorescence, as determined by the use of a microfluorimeter, on these agranular blasts was comparable to the positivity of lymphoid cells from acute and chonic lymphatic leukaemias. These findings lend further support to the conception of a lymphoblast-like variety of terminal blastic crisis in chronic myelogenous leukaemia.

Antigens, Surface↗