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Biomedical subjects

F Frassoni

Publications and source records attributed to F Frassoni.

At least 181 records · Page 10Linked to original sources
PubMed1984

High-dose chemotherapy and non-frozen autologous bone marrow transplantation in relapsed advanced lymphomas or those resistant to conventional chemotherapy.

Ten patients with advanced, diffuse Hodgkin's and non-Hodgkin's lymphomas responding poorly to the most widely employed primary chemotherapy regimens were treated with a high-dose chemotherapy (HDC) followed by rescue with non-frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in seven of ten patients (70%) and partial remission in two. Hemopoietic recovery occurred in nine cases. These preliminary results appear to indicate that HDC and non-frozen ABMT may be successfully used in patients with resistant or relapsed lymphomas.

Adult↗
PubMed1984

Cyclosporin A serum and blood levels in marrow graft recipients: correlation with administered dose, serum creatinine and graft-versus-host disease.

23 patients undergoing marrow transplantation for leukemia or aplastic anemia were given cyclosporin A (CyA) for graft-versus-host disease (GvHD) prophylaxis. A radioimmunoassay was used to monitor CyA serum levels in 13 patients and whole blood levels in 10. Serum creatinine levels were recorded daily until day 30 and then weekly. The severity of acute GvHD was recorded daily for a total of 1,738 patient days. CyA dose was then correlated with CyA serum or blood levels, serum creatinine levels and severity of acute GvHD. The daily dose of administered CyA correlated with serum CyA levels (p = 0.001) but not with whole-blood CyA levels. The cumulative CyA dose correlated with serum creatinine. There was an inverse correlation between the daily CyA dose and the severity of acute GvHD (p = 0.05). On the other hand the total amount of CyA given within 10 days after bone marrow transplantation had no influence on the severity of acute GvHD developing after day 10. Serum and whole-blood levels did not correlate with severity of GvHD nor with creatinine levels. The results of this study point out the nephrotoxicity of CyA, and a low GvHD score with high doses of administered CyA, at least on a daily basis. Serum but not blood levels reflect the dose of CyA given, but are not correlated with nephrotoxicity or GvHD.

Bone Marrow Transplantation↗
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

High dose bolus methylprednisolone for the treatment of acute graft versus host disease.

Nineteen patients with acute graft versus host disease (GvHD) following bone marrow transplantation (BMT) were treated with high dose bolus 6-methylprednisolone (BMPr), at the dose of 20 mg/kg/day i.v. for the first 3 days, 10 mg/kg/day i.v. for the following 4 days, and then at doses gradually tapered down to 1 mg/kg/day. All patients except one, who was given preventive BMPr 5 mg/kg/day i.v. on alternate days, were placed on preventive methotrexate therapy after BMT. Sixteen patients were grafted with an HLA matched, and three patients with an HLA mismatched marrow. Overall complete response rate in the HLA matched group was 43%, with an additional 50% showing a partial response. In the HLA mismatched group there were no responses and all three patients proved refractory to BMPr. With respect to organ involvement the complete and partial response rates were respectively 50% and 33% in the skin, 36% and 28% in the liver, 18% and 55% in the gut. Six of sixteen patients in the HLA matched group and none of the three in the HLA mismatched group are surviving. Thirteen patients died: nine patients for causes directly or indirectly related to GvHD, four of other causes (relapse, rejection, hemorrhage and idiopathic interstitial pneumonia). Side effects of BMPr consisted in hyperglicemia, and steroid associated gastritis in 2/3 of the patients, both of which responded well to conventional treatment. This study indicates that high dose BMPr is an effective form of treatment for established acute GvHD, and has no major side effects. The efficacy of BMPr is less clear in recipients of HLA mismatched grafts.

Adolescent↗
PubMed1983

Haemopoietic colony formation (BFU-E, GM-CFC) during the development of pure red cell hypoplasia induced in the cat by feline leukaemia virus.

The GM-CFC assay for granulocyte-macrophage progenitors and the BFU-E and CFU-E assay for early and late erythroid progenitors from cat bone marrow were characterized. GM-CFC gave 59 +/- 4 to 118 +/- 6 colonies per 10(5) bone marrow cells using colony stimulating factors (CSF) from cat, mouse or human sources. The CFU-E and BFU-E assays gave 114 +/- 7 and 58 +/- 7 colonies respectively with optimum doses of erythropoietin. Irradiated cat bone marrow cells were good sources of CSF and of burst promoting activity for these assays. Kittens infected with feline leukaemia virus, subgroup C (FeLV-C), which induces pure red cell hypoplasia, showed the incidence of BFU-E decreased to 25-35% of controls as early as one week postinfection, and even lower values at later times. In contrast, the incidence of GM-CFC remained normal for several weeks. No evidence of inhibitory cells or of lack of stimulatory cells in the infected marrows was seen when they were cultured together with normal marrow in the BFU-E assay. Conversely, normal marrow cells were not able to restore BFU-E growth from infected marrow. This suggests a direct action of FeLV-C on early erythroid precursors. Infection with FeLV, subgroup A, which induces only a mild transitory anaemia, produces only a moderate decrease in the incidence of BFU-E.

Anemia, Aplastic↗
PubMed1983

Fractionated total body irradiation in marrow transplantation for leukaemia.

Thirty consecutive patients with leukaemia were prepared for bone marrow transplantation (BMT) with cyclophosphamide (CY) 120 mg/kg followed by total body irradiation (TBI). TBI was delivered in a single dose (sTBI) of 10 Gy, at a dose rate of 0.06-0.08 Gy/min, or in fractionated doses (fTBI) of 3.3 Gy/d, on each of 3 consecutive days, at the same dose rate. Lung shielding was adopted for all patients, in order to obtain a homogeneous dose delivered to the lung and at midline. The first 12 patients were prepared with sTBI and the following 18 with fTBI. Several variables (remission status, mode of irradiation, prevention of graft versus host disease (GvHD) with methotrexate (MTX) or cyclosporin A(CyA) were then analysed for their influence on (a) incidence and mortality of GvHD, (b) incidence and mortality of interstitial pneumonia (IP), (c) 100-d survival, and (d) relapses. Our data suggest that fTBI is the single most important factor associated with a lower incidence of IP (P = 0.002), a lower mortality from GvHD and IP (P = 0.03 and 0.001) and a better 100-d survival (P = 0.03). Remission status had no significant influence on GvHD, IP and acute mortality. When compared to MTX, the use of CyA was associated with less GvHD and IP, but when only patients in remission given fTBI were analysed, this was no longer true. Relapses were mostly influenced by the remission status of the patient at transplant (P = 0.001). Although this is not a randomized study, our data suggest that fTBI can reduce the acute risks of marrow transplantation in leukaemia.

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↗
PubMed1983

Mepartricin: a new antifungal agent for the treatment of disseminated Candida infections in the immunocompromised host.

Mepartricin, a new semisynthetic heptene, was given for systemic Candida infections to 11 immunocompromised patients. All patients were undergoing bone marrow transplantation or treatment with antilymphocytic globulin: 6 had acute leukemia, 4 aplastic anemia and 1 had Wiskott-Aldrich syndrome. In all patients systemic Candida infection was diagnosed on the basis of fungemia or positive cultures from at least three different sites, two of which were outside the gut. Mepartricin was given intravenously as a slow drip, at the dose of 100-700 U/kg/day for a total of 198 patient-days (range 9-36, mean +/- SD 18 +/- 8). Patients had to be premedicated with steroids and antihistamines to avoid reactions such as chills and fever. The treatment was well tolerated in all patients, and renal function tests were unchanged during therapy. There was a complete resolution of the fungal infection in 10 of the 11 patients.

Adolescent↗
PubMed1983

Generation of CFUC suppressor T cells in vitro: VII. T derived colony inhibitory activity (Td/CIA) has no suppressor effect on in vitro immunoglobulin production.

T derived colony inhibitory activity (Td/CIA) was obtained from unstimulated T cells from aplastic anemia patients (SAA), or from PWM primed normal T cells. Td/CIA suppressed CFUC growth of normal allogeneic marrow to less than 30% of expected growth. Td/CIA was then added to normal peripheral blood T and B cells, primed with PWM, to test whether it would interfere with in vitro immunoglobulin (Ig) production. When Td/CIA from normal T cells was added to cultures of T + B cells + PWM there was a 2-2.1-fold increase in Ig production. Similarly the addition of Td/CIA from SAA patients also resulted in a 1.4 up to 166-fold increase in Ig production. These results indicate that either (a) the targets for Td/CIA are expressed on hemopoietic but not on T and B cells, or (b) that Td/CIA inactivates an accessory cell which is essential for CFUC growth but not for the PWM driven in vitro B cell differentiation system.

Anemia, Aplastic↗
PubMed1983

Treatment of severe aplastic anemia with sequential immunosuppression.

Forty-two patients with severe aplastic anemia (SAA) were treated with immunosuppressive therapy (IS) consisting of one or more courses of the following regimens: a) high dose bolus 6 methylprednisolone (BMPr); b) horse antilymphocytic globulin (HALG); c) rabbit ALG (RALG); d) ALG followed by the infusion of haploidentical marrow (ALG +/- BM); e) BMPr in combination with HALG; f) ALG in combination with androgens. All patients received one initial course of IS: 16 (38%) showed hematologic reconstitution and required no further transfusions, of 26 refractory patients 4 died, and 22 received a second course of IS 60 days after the first course. Of these 22, 6 (27%) responded, and of the 16 refractory patients, 9 died, and 7 received a third course of IS 60 days after the second course. Two of these responded (28%), 3 died and 2 are alive but pancytopenic. The overall response rate is 24/42 patients (57%): all of these patients are transfusion independent 6-60 months post-treatment, and 17 are off maintenance therapy with low dose steroids. The actuarial 5 year survival is currently 60%; 13/26 surviving patients have been followed for more than 3 years. The present study confirms that over 50% of patients with SAA can recover from their aplasia following IS treatment, and this is of relevance for patients who can not be offered a bone marrow transplant.

Adolescent↗
PubMed1982

GM-CFC growth in chronic granulocytic leukaemia is not affected by a soluble inhibitor released by aplastic anaemia T-cells or mitogen-primed normal T-lymphocytes.

Peripheral blood (PB) and bone marrow (BM) cells were obtained from 12 patients with chronic granulocytic leukaemia (CGL) and cultured in agar for granulocyte macrophage colony formation (GM-CFC). In addition PB and BM CGL cells were co-cultured with T-lymphocytes from patients with immune severe aplastic anaemia (SAA), or with T-cells from healthy donors primed with pokeweed mitogen (PWM). The supernatants of SAA and PWM primed T-cells were also added to CGL cells grown in agar. Normal marrow cells obtained from eight healthy donors were used to set up control cultures and co-cultures. The results of this study indicate that, firstly, T-cells derived from SAA patients and their supernatants suppress GM-CFC growth of normal marrow cells but not of PB nor BM CGL cells, and, secondly, normal T-cells primed with PWM and their supernatants suppress normal marrow GM-CFC but not colony formation of BM nor PB CGL cells. These results provide further evidence that mediators which are effective in regulating normal myeloid progenitor cells fail to inhibit the in vitro growth of GM-CFC from CGL patients.

Adult↗
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

The relative spatial distribution of erythroid progenitor cells (BFUe and CFUe) in the normal mouse femur.

Femoral mouse bone marrow cells were separated into axial and marginal fractions, in order to investigate the relative concentration of erythroid progenitor cells (BFUe and CFUe) with respect to their location across the diameter of the femur. Two areas of high incidence of early progenitor cells (BFUe) were identified: one lying near the bone surface with a peak at about 410 micrometers radial distance from the axis of the bone; the other nearer the centre of the bone with a peak at about 270 micrometers. The more immature BFUe were found in higher proportion in the marginal peak. In contrast, CFUe, apart from very low concentration values in the vicinity of the bone surface, demonstrated a fairly uniform distribution throughout the marrow. The present results indicate that the distribution of erythroid progenitor cells within the bone marrow is not random. The haemopoietic tissue seems to exhibit a well-defined structure that may be relevant in regulating proliferation and differentiation processes.

Animals↗