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Biomedical subjects

F Frassoni

Publications and source records attributed to F Frassoni.

At least 145 records · Page 8Linked to original sources
PubMed1990

Allogeneic bone marrow transplantation for leukemia in Europe: regional differences. Report from the Leukemia Working party of the European Group for Bone Marrow Transplantation.

The results of 1904 allogeneic HLA identical sibling donor bone marrow transplants performed in 52 European centers between 1979 and 1986 and reported to the EBMT leukemia registry were analysed by geographical location of the transplant. Patients were grouped into six regions: United Kingdom, Nordic Group, Benelux, France, Central Europe and Southern Europe. There were significant differences between these regions with respect to patient population and outcome. The relative proportion of the three major disease categories, stage and subtype of the diseases, graft-versus-host disease prevention methods, donor recipient sex combinations, age of the patient, year of the transplant and the time intervals from diagnosis to transplant, from diagnosis to first complete remission for acute leukemia and the time from first complete remission to the transplant varied from region to region. The analysis of outcome parameters showed a significant difference in relapse incidence from region to region. This influence of region was confirmed in a multivariate analysis and was independent of the other factors known to affect outcome. Leukemia-free survival and transplant-related mortality were not different. The reasons for these differences could not be explained by the data in the registry. We conclude that regional factors must be considered when bone marrow transplant data are compared and we postulate that pretransplant factors probably affect outcome more than was previously realized.

Adolescent↗
PubMed1989

Cytogenetic follow-up after bone marrow transplantation for Philadelphia-positive chronic myeloid leukemia.

Forty-eight consecutive patients affected by chronic myelogenous leukemia (CML) Philadelphia (Ph) chromosome positive during the chronic phase of the disease underwent allogeneic bone marrow transplantation (BMT). Thirty-five patients had a follow-up over 12 months and were included in a cytogenetic study in order to evaluate the Ph clone eradication. In 25 cases, the Ph chromosome disappeared in all cytogenetic studies, and their hematologic picture is at present apparently normal. Ten patients showed cytogenetic relapse. In one case, the cytogenetic relapse was transitory without any clinical sign of the disease; in three cases, after a transitory cytogenetic relapse, a persistent relapse with clinical picture of progression of the disease occurred; in six cases cytogenetic and a clinical relapse were coincident. Structural chromosomal abnormalities other than Ph were temporarily seen in three cases. The so-called "nonrandom" chromosomal changes typical of the blastic phase were never detected. The reappearing Ph-positive clone spontaneously disappeared in three patients, and their hematologic picture reverted to complete chimerism. The present study confirms that the eradication of the Ph clone is often defective with BMT, and cytogenetic analysis can detect the competition between donor and residual host marrow. Furthermore, the karyotype evolution is different from that found in CML patients treated with conventional chemotherapy.

Bone Marrow↗
PubMed1989

Molecular analysis of Philadelphia-negative myeloproliferative syndromes with i(17q).

We report two cases of myeloproliferative syndromes in which the only karyotypic abnormality was an isochromosome of the long arm of chromosome 17. Because i(17q) is a nonrandom structural aberration found in nearly 12% of cases of Philadelphia (Ph)-positive chronic myelogenous leukemia (CML), we carried out a molecular analysis of the breakpoint cluster region (bcr) to verify the presence of genomic rearrangements characteristic of CML. The interest of the study was strengthened by the fact that i(17q) is frequently seen in CML and by recent reports showing that genomic changes of c-abl and bcr genes can be present even in the absence of a Ph chromosome. One of the two patients showed the presence of a rearranged fragment within the bcr, suggesting a Ph-positive CML diagnosis.

Adult↗
PubMed1989

Total body irradiation in acute myeloid leukemia and chronic myelogenous leukemia: influence of dose and dose-rate on leukemia relapse.

From June 1981 to March 1987, 106 patients--59 with acute myeloid leukemia (AML) and 47 with chronic myelogenous leukemia (CML)--were treated with Cyclophosphamide 60 mg/kg X 2 d and total body irradiation (TBI-990 cGy/3fr/3d described dose) before allogeneic bone marrow transplantation. Seventy-nine patients are evaluable for risk of relapse: 32 with chronic myelogenous leukemia (23 in first chronic phase, 9 in accelerated phase) and 47 with acute myeloid leukemia (38 in first complete remission, 9 in subsequent phases). Actual TBI doses delivered to these patients varied between 839 and 1250 cGy (mean 956 +/- 101)/3 fr/3d, with dose rates between 2.7 and 7.25 cGy/min (mean 4.2 +/- 1.8). Patients receiving high (greater than 990 cGy) and low (less than or equal to 990) dose and/or dose rate (greater than 4 cGy/min and less than or equal to 4, respectively) have been evaluated overall and stratified by type of leukemia and phase of disease. When the patients are considered altogether, high total dose is significantly correlated with decreased risk of relapse (p = 0.0005) as well as high dose rate (p = 0.03). When considering specific subgroups, the influence of total dose on relapse rate is evident both for "early" and "advanced" leukemias, while an impact of dose rate appears only for chronic myelogenous leukemia in 1st chronic phase. Pertinent radiobiological and clinical literature is reviewed, and a possible role of dose fractionation and dose rate in leukemic control rate is evidenced; in this TBI setting, total dose not less than 990 cGy/3fr/3d and dose rate not less than 4 cGy/min have to be guaranteed.

Adolescent↗
PubMed1989

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation.

One-hundred and five patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n = 61) and chronic myeloid leukaemia (n = 44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. There was a difference of +/- 18% between the nominal total dose of 990 cGy and the actual dose received as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival (4%) there was a considerable difference in the incidence of relapses. The incidence of relapse was 55% versus 11% in patients receiving less or more than 990 cGy respectively and this had a major impact on survival (38% v. 74% at 7 years) since transplant-related mortality was comparable in the two groups. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%. 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GVHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced but a small reduction of the dose may significantly increase the risk of relapse.

Adolescent↗
PubMed1989

[Fractionated and hyperfractionated total body irradiation in the conditioning of allogenic bone marrow transplant in acute lymphatic leukemia. Results].

Two different Total Body Irradiation (TBI) regimens were employed (1981 to July 1983) in Genoa in the conditioning program for the allogeneic Bone Marrow Transplantation (BMT) of 22 patients suffering from Acute Lymphoblastic Leukemia (ALL) in remission (7 patients in 1st remission, and 15 in 2nd remission). All patients were treated with Cyclophosphamide -60 mg/kg administered for two consecutive days (day -7 and -6)--and subsequently underwent fractionated TBI (days -3, -2, -1), that is, our conventional TBI regimen: 3.3 Gy/day per 3 days (total dose: 9.9 Gy). From August 1983 through 1988, 33 patients (14 in 1st remission and 19 in 2nd remission) were given 2 Gy twice a day, 6 hours apart, for 3 consecutive days (total dose: 12 Gy). Cyclosporine A was used for GvHD prophylaxis. At 58 months, out of the total figure of ALL patients in 2nd remission, 19% of those treated with 9.9 Gy/3 fr/3 days (fractionated TBI) is likely to be in remission, versus 65% of the cases treated with 12 Gy/6 fr/3 days (p less than 0.01) (hyperfractionated TBI); the actuarial overall survival is 23% after fractionated vs 60% after hyperfractionated TBI (p = 0.05). The incidence of idiopathic interstitial pneumonitis was very low (3.6%). Thus, we conclude that, in ALL patients in second remission, hyperfractionated TBI (12 Gy/6 fr/3 days) yields better results than fractionated TBI (9.9 Gy/3 fr/3 days), with lower relapse rate (33% vs 83%) and higher survival.

Adolescent↗
PubMed1988

Variant Philadelphia translocations in CML: correlation with fragile sites.

Of 175 CML patients studied, 14 variants were found, seven of which are presently described. The breakpoints involved in the translocation, other than 9q34 and 22q11, are 3p21, 5q13, 6p21, 7q22, 10q22, and 11p13. Fragile sites were investigated in some of these patients. In two cases a coincidence between fragile site location and breakpoint of the third chromosome involved in Philadelphia formation was found. This observation suggests that the fragile sites can lead to Ph variants in patients developing CML.

Adult↗
PubMed1988

ABO compatibility and acute graft-versus-host disease following allogeneic bone marrow transplantation.

If ABO antigens/antibodies play any role in the pathogenesis of acute graft-versus-host disease (GVHD), one would expect the highest incidence of GVHD in recipients of minor ABO-mismatched grafts, followed by ABO-matched grafts, and the lowest incidence in major ABO-mismatched transplants. To test this hypothesis 174 patients receiving an HLA-identical allogeneic bone marrow transplant (BMT) for aplastic anemia (n = 32) or leukemia (n = 142) were analyzed for factors associated with acute GVHD. Variables analyzed included diagnosis, sex, age, blood group of donor and recipient, ABO compatibility, Rhesus compatibility, sex compatibility, number of bone marrow cells given at BMT, year of transplant, day of engraftment, and GVHD prophylaxis. We first carried out an exploratory contingency table analysis: minor ABO incompatibility was associated with a significantly higher risk of severe acute GVHD when compared with ABO-matched and major-ABO mismatched pairs (P = 0.003): 14/9, 57/67, and 5/22 patients developed, respectively, 0-I/II-IV acute GVHD in ABO major-mismatched, matched, and minor-mismatched pairs. Donors of group 0, (P = 0.06), older recipient's age (P = 0.08), fast engraftment (P = 0.03), and older donor's age (0.08) were also associated with a higher risk of GVHD. Recipient's ABO group, diagnosis, year of transplant, Rhesus group of donor or recipient, Rhesus compatibility, sex of donor or recipient, sex compatibility, and type of GVHD prophylaxis were not predictive of GVHD. A Cox multifactorial proportional hazards analysis confirmed that ABO matching was the single most significant factor associated with GVHD (P = 0.006). The cumulative incidence of GVHD grade II+ was 39%, 54%, and 82% for ABO major-mismatched, matched, and minor-mismatched pairs (P = 0.01). This study suggests that ABO antigens may play a role in the development of acute GVHD.

ABO Blood-Group System↗
PubMed1988

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia.

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.

Acute Disease↗
PubMed1988

Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases.

A multi-centre retrospective analysis on 117 patients relapsing after bone marrow transplantation (BMT) for acute leukaemia was carried out by the Leukaemia Working Party of the European Group for Bone Marrow Transplantation (E.B.M.T.). Forty-one patients had acute myeloid leukaemia (AML) and 76 had acute lymphoblastic leukaemia (ALL). Relapse occurred between 3 and 30 months after BMT and where investigated the leukaemia was found to have relapsed in recipient cells. In 10 cases the relapse was associated with new cytogenetic abnormalities. 74 patients received further treatment for leukaemia. Of these 21 out of 50 with ALL and 11 out of 24 with AML achieved a complete remission and had a median survival of 12 months compared with a median survival of 4 months for untreated patients or patients not achieving complete remission (P less than 0.001). Factors predictive for successful remission induction were a long interval between bone marrow transplant and relapse in ALL patients; and isolated extramedullary relapse. Presenting blast count, karyotype and remission status and number at the time of BMT were not predictive. Donor bone marrow was shown to be responsible for haemopoietic recovery occurring in the 21 out of 31 patients tested who achieved remission using donor karyotype or red blood cell antigens as markers. Nine patients received a second bone marrow transplant but only one became a long-term survivor. The results show that chemotherapy can usually prolong survival in selected patients with acute leukaemia relapsing after BMT but further BMT has a poor outlook.

Adolescent↗
PubMed1988

Relapse after allogeneic bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia: cytogenetic analysis of 24 patients.

One hundred patients with chronic myeloid leukemia (CML) submitted to bone marrow transplantation (BMT) were included in a cooperative cytogenetic study. Relapse (defined on the basis of hematological and cytogenetic findings) occurred in 24 (24%) patients at different intervals after BMT. In 18 of these patients (studied on average 3.3 times between BMT and relapse) no Ph-positive metaphases were detected before relapse. Sixteen (75%) of the patients relapsed with the same chromosomal pattern as that seen before BMT; eight patients, of whom five relapsed in blast crisis, showed additional chromosomal abnormalities resembling those seen in non-transplanted patients. One of these patients relapsed in cells of donor origin. After recognition of relapse, various hematological and cytogenetic patterns were observed. Four patients showed spontaneous reversion to normal (donor-type) chromosomes and hematology. Two other patients were followed for prolonged periods with hypercellular marrows with more than 50% Ph-positive cells but with normal peripheral blood values. The majority of patients proceeded to clinical relapse and required treatment with chemotherapy. We conclude that the isolated finding of a minority of Ph-positive metaphases after BMT should not be classified as relapse; for patients who do relapse, the sequence of cytogenetic and hematological events thereafter is variable.

Adolescent↗
PubMed1988

T cells and myeloid progenitors in patients with severe aplastic anemia (SAA).

This report summarizes some of our past and present studies on T cells and hemopoietic progenitors obtained from patients with severe aplastic anemia (SAA). Two main issues are discussed: enhancement of colony growth by manipulation of accessory cells, or by the addition of patients' plasma, and the role of suppressor T cells in the pathogenesis of the disease and response to antilymphocyte globulin (ALG). A complex network of interactions exists. The identification of cells and soluble factors capable of enhancing or suppressing colony formation promises to help us better understand the events leading first to the development of aplasia and then eventually to hematologic recovery.

Anemia, Aplastic↗