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Biomedical subjects

F Frassoni

Publications and source records attributed to F Frassoni.

At least 163 records · Page 9Linked to original sources
PubMed1987

Human serum-dependent survival of GM-CFCs in vitro from patients with chronic granulocytic leukemia.

Bone marrow (BM) cells from 15 patients with chronic granulocytic leukemia (CGL) and 12 normal donors were placed in liquid culture for 4-7 days in the presence of fetal calf serum (FCS) or human AB serum. BM cells were plated in agar for GM-CFC growth at day 0, day 4, day 7 of culture, in the presence of human placenta conditioned medium (HPCM). The recovery of GM-CFCs on day 4 in FCS was 86 +/- 18 and 15 +/- 18% from normal or CGL BM cells respectively (p = 0.005). The recovery of GM-CFCs on day 4 in human AB serum was comparable for normal (66 +/- 48%) and CGL (69 +/- 32%) BM cells. Similar results were obtained on day 7 of culture. Cytochemical staining of agar plates showed a sharp drop of macrophage colonies in CGL BM cells kept in FCS cultures on day 4-7, when compared to both normal BM cells and baseline colonies. These data suggest that the survival in liquid culture of GM-CFCs from patients with CGL is dependent on a factor present in human and not in fetal calf serum. This is not the case for normal GM-CFCs.

Animals↗
PubMed1987

Poor graft function associated with graft-versus-host disease after allogeneic marrow transplantation.

This is a retrospective analysis of marrow function in 171 recipients of an HLA-matched bone marrow transplant (BMT). Only patients with detectable hemopoiesis as indicated by leukocyte counts greater than 1.0 x 10(9)/l and platelet counts greater than 25 x 10(9)/l who were alive on day 30 were entered in the study. Poor marrow function was detected in 24 (14%) patients as indicated by a decrease in the peripheral blood counts to less than 40% of the maximal preceding values post-transplant in association with reduced marrow cellularity. Leukopenia (n = 4), thrombocytopenia (n = 3) or a combination of the two (n = 17) occurred 62 +/- 23 (SEM) days post-transplant and was associated with acute graft-versus-host disease (AGVHD) grade II or more and infection (n = 19) in the absence of clear rejection or persistence/recurrence of malignant disease. A multivariate analysis showed that AGVHD was the major risk factor (p = 0.001) for developing poor graft function. In the 24 patients with poor graft function, hemopoietic recovery was strongly associated with resolution of AGVHD and of infections. Their survival (27%) was the same as survival for other patients matched for GVHD who had no pancytopenia. The causes of death were GVHD (n = 13), pneumonia (n = 3) and infections (n = 1). This study draws attention to a particular type of poor graft function following allogeneic BMT that is characterized by (1) normal timing and quality of engraftment, (2) AGVHD of grade II or greater, (3) progressive and severe pancytopenia, and (4) multiple infections with poor clinical condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗
PubMed1986

Bone marrow transplantation for chronic granulocytic leukemia.

Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.

Adolescent↗
PubMed1986

Acute myelogenous leukemia with translocation t(8;21): a cytogenetic study of seven cases.

Seven cases of acute nonlymphoblastic leukemia showing t(8;21)(q22;q22) at diagnosis are described. Involvement of a sex chromosome was found in all patients (in six cases as a loss, and in one as a Y duplication), thus, confirming the suggestion of a correlation between these two chromosomal abnormalities. The constitutional folic acid-sensitive fragile site fra(8)(q22) was not detected, in spite of careful analysis of over 300 metaphases of cells grown in folic acid-free medium. Morphologic diagnoses and clinical aspects are briefly discussed.

Adult↗
PubMed1986

Competitive survival/proliferation of normal and Ph1-positive haemopoietic cells.

Bone marrow (BM) cells from 10 patients with Ph1-positive chronic granulocytic leukaemia (CGL) were placed in long-term cultures in the presence of fetal calf serum (FCS) and horse serum (HoS), or in the presence of human AB serum. The long-term cultures were started with three different cell combinations: (1) CGL BM cells (four cases), (2) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex-matched sibling (five cases), (3) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex mismatched sibling (five cases). Cytogenetic studies were performed at weeks 0, 3, 4 and 5 of culture. The results of this study can be summarized as follows: (a) Ph1-positive cells could be detected at any time of culture in all three of the described cell combinations; (b) a population of Ph1-negative cells of patient origin could be detected after 3-5 weeks of culture; (c) there was a trend for a better survival of Ph1-negative cells in cultures supplemented with FCS + HoS and, conversely, of Ph1-positive cells in cultures containing human serum. These results warrant further studies on the possibility of manipulating survival and proliferation of normal and leukaemic cells by varying the culture conditions.

Bone Marrow↗
PubMed1986

Allogeneic bone marrow transplantation versus chemotherapy for childhood acute lymphoblastic leukaemia in second remission.

Thirty-six children with acute lymphoblastic leukaemia (ALL) in second remission were treated with conventional chemotherapy or with cyclophosphamide and fractionated total-body irradiation followed by an allogeneic bone marrow transplant; the choice of treatment was dictated by the availability of an HLA-identical sibling. The age, sex, clinical data at presentation of the disease and duration of first remission were comparable for the two groups of patients. In the bone marrow transplantation group two patients died of graft-versus-host disease and five of leukaemia. Ten patients survive, nine disease free, 13-53 months from second remission (6-51 months post-bone marrow transplantation). In the chemotherapy group 14 patients died of leukaemia (2-29 months from second remission) and five survive (22-34 months from second remission). The actuarial survival for patients with bone marrow transplantation is 48% at 4 years as compared with 22% for those of the chemotherapy group (P = 0.04); the actuarial probabilities of being in remission are 58 and 18% in the two groups respectively (P = 0.01). This study confirms that allogeneic bone marrow transplantation is superior to chemotherapy in patients in second remission with ALL and should be considered in the presence of an HLA-identical sibling.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Massive chemotherapy with non-frozen autologous bone marrow transplantation in 13 cases of refractory Hodgkin's disease.

A group of 13 patients with advanced, diffuse Hodgkin's disease, poorly responding to the most widely employed primary chemotherapy regimens, were treated with massive chemotherapy (MCH) followed by rescue with non-frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in 8/13 patients (61.5%) and partial remission in two. Hematopoietic recovery occurred in 12 cases. These preliminary results would seem to indicate that MCH with non-frozen ABMT may be successfully used in patients with resistant or relapsed Hodgkin's disease.

Adolescent↗
PubMed1985

In vitro tests in severe aplastic anaemia (SAA): a prospective study in 46 patients treated with immunosuppression.

Forty-six patients with severe aplastic anaemia (SAA) were studied for CFU-c growth on admission and 1 month post-treatment with immunosuppression (IS). Twenty-three patients became transfusion independent after IS, and were considered responders, and 23 did not. CFU-c growth from unfractionated bone marrow cells was comparable in both groups on admission and 1 month post-treatment. CFU-c growth from E rosette depleted BM cells (E-BM) was also comparable on admission. However, 1 month post-treatment, responders showed a significantly higher CFU-c growth (P = 0.02) from E-BM cells compared to non-responders. At the same time 7/8 responders studied showed T cell mediated suppression of autologous CFU-c growth. T cell depletion experiments do not give predictive information on the outcome of IS therapy on admission. They may, however, be helpful to identify responders early post-treatment.

Adolescent↗
PubMed1985

Cyclosporin A (CyA) does not enhance CFU-c growth in patients with severe aplastic anaemia.

8 patients with severe aplastic anaemia (SAA) in remission following immunosuppressive therapy were studied for CFU-c growth from unfractionated or E-rosette depleted (E-) bone marrow (BM) cells. Cyclosporin A (CyA) was added to unfractionated BM cells at a concentration of 1000 ng/ml. The mean number of CFU-c/10(5) BM cells plated was 6 +/- 6 from unfractionated BM cells, 28 +/- 20 from E-BM cells, and 8 +/- 7 from unfractionated BM cells supplemented with CyA. All patients had significant increase of CFU-c growth after E rosette depletion (overall P = 0.002). On the contrary, only 1 patient showed an increase of CFU-c growth after addition of CyA, and overall there was no difference between untreated and CyA treated BM cells (P = 0.7). These results suggest that addition of CyA to BM cells in vitro is not an effective means of enhancing CFU-c growth in SAA patients.

Adolescent↗
PubMed1985

Bone marrow transplantation (BMT) for acute nonlymphoid leukemia (ANLL) in first remission.

20 patients with acute nonlymphoid leukemia (ANLL) in first remission were given cyclophosphamide, 120 mg/kg, followed by total body irradiation (TBI) and an HLA-identical allogeneic marrow transplant (BMT). TBI was delivered in a single dose (10 Gy on day -1) in 2 patients, or in fractionated doses (3.3 rad/day on days -3, -2, -1) in 18 patients. The median age of patients was 22 years (range 2-44). Median time from remission to BMT was 5 months (range 1-12). 5 patients died of transplant-related toxicity (graft-versus-host disease with or without interstitial pneumonia) and 15 are alive 7-77 months post-BMT (median 20). The actuarial 72 months survival is 73%. There has been one relapse in a 2-year-old child, 4 months post-BMT, in the marrow and in the testis. The 72-month actuarial disease-free survival is 68%. The actuarial probability of relapse is 7%. This study indicates that a high proportion of ANLL patients treated in first remission with fractionated TBI and allogeneic marrow transplantation can become long-term disease-free survivors.

Acute Disease↗
PubMed1985

T-derived colony-inhibiting activity: partial characterization and mechanism of action.

A soluble inhibitor of granulocyte macrophage colony growth, to which we shall refer to as T-derived colony-inhibiting activity (Td/CIA), was obtained from the supernatant of T cells from 5 healthy donors and 5 patients with severe aplastic anemia (SAA) in remission, following immunosuppressive therapy. The supernatants were purified by an ACA 44 column and the suppressor activity found in fractions of 70,000-80,000 daltons. Experiments were then performed to test for endogenous productions of Td/CIA in normal marrow cells (NBM), reversibility of suppression, and competitive inhibition with human placenta-conditioned medium (HPCM). The results of this study can be summarized as follows: the endogenous production of Td/CIA can be elicited by addition of mitogens to NBM, and is prevented if the marrow is T-depleted or treated with cyclosporin A; suppression is completely reversible if Td/CIA is removed from NBM by washing at 1, 48, 72 and 96 h; CFU-c which have been exposed to Td/CIA once, and freed from Td/CIA by washing, are still sensitive to a second exposure of Td/CIA; there is no clear competitive inhibition between Td/CIA and HPCM. These experiments represent an in vitro model of a lymphokine-mediated regulation of CFU-c growth not associated with death of progenitor cells.

Bone Marrow Cells↗
PubMed1985

Effect of cyclosporin A (CyA) on the in vitro growth of hemopoietic progenitors from normal marrow.

Unfractionated normal bone marrow cells (NBM), adherent-cell-depleted NBM, and E-rosette-depleted NBM were plated in vitro for CFU-c or BFU-E formation at plateau concentrations of colony-stimulating activity (CSA) or erythropoietin, untreated or after preincubation with cyclosporin A (CyA). At concentrations of 1000 or 2000 ng/ml, CyA enhanced CFU-c growth up to 137 +/- 32% and 147 +/- 31% of expected baseline growth respectively (p = 0.005 and 0.001). When CyA was added to NBM depleted of T cells by rosetting once with sheep red blood cells (SRBC) there was no CFU-c enhancement at CyA concentrations of 1000 ng/ml, but enhancement could be seen at 2000-5000 ng/ml. The enhancing effect of CyA was completely abolished, however, when the SRBC rosetting procedure was repeated twice (95 +/- 37% of expected growth). On the other hand, removal of adherent cells was without effect on CFU-c enhancement mediated by CyA. The addition of CyA to NBM also enhanced the growth of BFU-E (256 +/- 182% of expected growth) (p = 0.001). The results of this study suggest that CyA can increase the plating efficiency of NBM cells, possibly by inhibiting an endogenous, T-cell-mediated, suppressor mechanism.

Bone Marrow Cells↗
PubMed1985

Cyclosporin A in marrow transplantation for leukemia and aplastic anemia.

A total of 29 consecutive patients with leukemia or aplastic anemia who received an HLA-identical marrow graft were given cyclosporin A (CyA) to prevent graft-versus-host disease (GvHD). These patients were compared with an historic group of 25 similar patients with leukemia or AA given methotrexate (MTX) for GvHD prophylaxis at this institution. Engraftment was faster in patients given CyA when compared with MTX patients, with less days of granulocytopenia (P = 0.04), a shorter interval before reaching a platelet count of 70 X 10(9)/l (P = 0.04), fewer major infections (P = 0.01), and fewer days on intravenous antibiotics (P = 0.02). There were no graft failures in CyA patients compared with four of 25 in MTX patients (P = 0.01). Early mortality was lower in CyA patients but not significantly (P = 0.06). The incidence of pulmonary complications was comparable, five of 29 and seven of 25 in CyA and MTX patients, respectively, but the clinical features of such complications differed. Interstitial pneumonia developing after day 30 was seen in MTX patients, whereas an acute respiratory distress syndrome developing between day +8 and day +18 was seen in CyA patients. Acute GvHD was less severe in CyA patients (P = 0.04), but chronic GvHD was comparable (P = 0.3). The actual one-year survival is currently 72% and 52% in CyA and MTX patients, respectively (P = 0.1). Although our initial experience with CyA is encouraging with regard to engraftment and acute GvHD, optimization of CyA protocols will probably be needed for it to be proven as having a definite advantage over MTX.

Adolescent↗
PubMed1985

Cytochemical analysis of peripheral blood mononuclear cells following allogeneic bone marrow transplantation: correlation of hydrolase expression with graft-versus-host disease.

Peripheral blood mononuclear cells of 21 patients undergoing allogeneic bone marrow transplantation (BMT) were monitored post-BMT for immunologic markers (E rosettes OKT3, OKT8, DR, and BT5/9, a monoclonal antibody which stains helper T cells), cytochemical markers (acid phosphatase [AP], beta-glucuronidase [BGLU], and acid alpha naphthyl acetate esterase [ANAE] ), and morphology. The cytochemical T score, was obtained from typical AP, BGLU, and ANAE reactivity. The same was done for the cytochemical non-T score and macrophage (Mo) score. All patients received cyclosporine A (CyA) for graft-v-host disease (GvHD) prophylaxis. In univariate analysis there was no significant correlation between the proportion of E rosettes, OKT3-, OKT8-, DR-, and BT5/9-positive cells, and GvHD. The first three showed instead a positive correlation with time from transplant: E rosettes (P = .02), OKT3 (P = .01), and OKT8 (P = .003). In contrast, a significant negative correlation was found in univariate analysis, between the cytochemical T score and GvHD (P = .0001), and a positive correlation between non-T score and GvHD (P = .0008), as well as between the Mo score and GvHD (P = .03). There was no influence of time from transplant on the T (P = .8), non-T (P = .8), or Mo score (P = .4). In multivariate analysis comparing E rosettes, OKT3, T score, non-T score, GvHD, and time from BMT, the only variable associated with GvHD was the T score (P less than .05). These results suggest that T cell activation during GvHD is associated with a loss of hydrolase expression in T cells, but does not imply relevant modifications of immunologic surface markers. In addition, lysosomal enzymes appear early (before day 10) after transplantation, indicating that T cells at this stage are well differentiated.

Anemia, Aplastic↗