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F Carbonell

Publications and source records attributed to F Carbonell.

At least 19 recordsLinked to original sources
PubMed1990

Isochromosome 17q in Ph1-negative leukemia: a clinical, cytogenetic, and molecular study.

We report on eight patients who were 35 to 77 years old with an isochromosome 17q as the sole structural chromosomal anomaly. Additional numerical chromosomal changes were a trisomy 8 or 17 in two cases each and a trisomy 19 in one case. Five patients had myelodysplastic syndrome (MDS) diagnosed according to the FAB nomenclature as chronic myelomonocytic leukemia (CMML) in two cases, refractory anemia with excess of blasts in transformation (RAEBt) in two cases, and refractory anemia with excess of blasts (RAEB) in one case. One patient suffered from a myeloproliferative disorder (MPS). All cases progressed to acute nonlymphocytic leukemia (ANLL) type M1, M2, or M4 in a period of 2 to 30 months after initial diagnosis, except one patient with RAEBt who died within 2 months. Two patients presented with ANLL-M2 at time of diagnosis. Treatment during the chronic phase of disease consisted of mild cytoreduction and/or substitution of platelets or red blood cells. One patient with CMML received an allogeneic bone marrow graft and relapsed after 33 months with ANLL-M1. Treatment results for overt leukemia were poor, and survival was short, lasting from 1 to 4 months. Overall survival was 1 to 37 months (median duration, 6.5 months). Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene, as observed in Ph1-positive chronic myeloid leukemia (CML). Thus, an i(17q) anomaly seems to identify a distinct subgroup of mostly myelodysplastic and, less frequently, myeloproliferative disorders that progress rapidly to ANLL, respond poorly to chemotherapy, and are associated with short survival after transformation.

Acute Disease↗
PubMed1990

An enzyme-linked antiglobulin test for assessing anti-D immunoglobulin preparations.

Two enzyme-linked antiglobulin tests (ELAT) for assessing anti-D IgG preparations are described; one is performed in tubes and the other in microtitre plates. An anti-human IgG alkaline phosphatase conjugate and the substrate p-nitrophenyl phosphate are used. Both methods were sensitive and reproducible, with variations coefficients of 7.8 and 8.6% for enzyme immunoassay in tubes and microplates, respectively. The linear relationship between the amount of red cell-bound anti-D and the optical density shows that the method is suitable for quantitative studies. Results obtained by the two methods show a very good correlation (r = 0.99) in 12 of the 14 samples assayed, and both give good agreement with results obtained in automated haemagglutination. Since microtitre plate ELAT has numerous advantages over the tube method, it could provide an alternative method for assessing anti-D activity of specific IgG preparations in control laboratories.

Antibodies, Anti-Idiotypic↗
PubMed1990

[Evaluation of 196 patients with chronic myeloid leukemia based on a standard prognosis model].

The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.

Biomarkers, Tumor↗
PubMed1989

Evaluation of remission state in chronic myeloid leukemia patients after bone marrow transplantation using cytogenetic and molecular genetic approaches.

The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.

Adolescent↗
PubMed1988

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients.

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.

Adult↗
PubMed1988

Translocation (15;17) in acute promyelocytic leukemia in Germany.

We report on the cytogenetic findings in six cases of acute promyelocytic leukemia, studied in two different cytogenetic laboratories in Germany. A t(15;17) was detected in three cases. This finding reveals that the t(15;17) in acute nonlymphocytic leukemia type FAB M3 also exists in Germany as a nonrandom anomaly and indicates that it occurs with high frequency in this country.

Adult↗
PubMed1988

Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia.

Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.

Adolescent↗
PubMed1987

Acute myelofibrosis in megakaryoblastic leukemia with translocation between chromosomes 8 and 14.

In a 45-year-old woman with severe normochromic anemia (Hb 2.8 g%) an extensive myelofibrosis and infiltration of the bone marrow with small blasts was observed histologically. Cytochemical examination of the blasts showed a negative peroxidase and a strongly positive alpha-NE reaction. PAS reaction was slightly granular positive in the cytoplasmic protuberances of the blasts and in the platelets. Marker analysis yielded no evidence of lymphatic origin of the blasts. In flow-cytometric studies of 230,000 cells a homogeneous 2c blast population could be identified. Cytogenetic analysis revealed an abnormal pseudo-diploid karyotype characterized by 2 acrocentric marker chromosomes caused by a translocation of chromosomes 8 and 14, as usually seen in Burkitt type lymphoma. Finally the reaction product of platelet-specific peroxidase could be demonstrated in the perinuclear cisternae of the endoplasmic reticulum by electron microscopy. Highly elevated beta-thromboglobulin and platelet factor 4 plasma levels were also measured. Following an ineffective treatment with daunoblastine and ARA-C, the patient died of pseudomonas aeruginosa septicemia after having received high-dose ARA-C treatment.

Biopsy, Needle↗
PubMed1987

Trisomy 15 as a regular finding in chemically induced murine T-cell leukemogenesis.

Trisomy 15 is described as a common finding in all T-cell leukemias induced by a single dose of methylnitrosourea (MNU) in BDF1 mice and in the leukemias induced by 7 doses of benzo(a)pyrene. Additional trisomies were found in about half of the leukemias. The organ distribution suggests that the leukemic cells with trisomy 15 originate in the thymus. Trisomy 15 was detected in the thymus as early as 6 weeks after the application of MNU, i.e. during the latency period.

Animals↗
PubMed1987

Chromosome studies in patients with Philadelphia chromosome-positive chronic myeloid leukemia submitted to bone marrow transplantation--results of a European Cooperative Study.

The karyotypes of 74 patients with Ph-positive chronic myeloid leukemia submitted to bone marrow transplantation collected from nine institutions were studied serially before and after transplantation. In 13 cases sporadic Ph-positive metaphases were detected without signs of relapsing disease at various intervals after transplantation. These data indicate that the leukemic clone may not be completely suppressed by the conditioning treatment and that other biological mechanisms may be involved in destroying this clone or controlling its expansion.

Adolescent↗
PubMed1987

Chromosome studies in patients with acute nonlymphocytic or acute lymphocytic leukemia submitted to bone marrow transplantation--results of a European cooperative study.

The chromosomal data of 58 acute nonlymphocytic leukemia (ANLL) patients and of 32 acute lymphocytic leukemia (ALL) patients submitted to bone marrow transplantation and collected from nine institutions are reported. Chromosomal studies were available at diagnosis in 19 cases with ANLL: seven had a partially or completely abnormal pattern. Forty-one patients had a chromosome study before bone marrow transplantation and all had a normal pattern. Thirteen patients with ALL were studied at diagnosis: five had a partially or completely abnormal karyotype. Of 20 cases analyzed before bone marrow transplantation, only one has maintained the abnormal pattern of diagnosis in part of the cells. Karyotypes were available in nine ANLL patients relapsed after bone marrow transplantations. Two showed the same clonal abnormalities seen at diagnosis; in three other cases the leukemic clone of relapse carried an additional chromosome abnormality with respect to the pattern at diagnosis and four more cases presented at relapse complex abnormalities; two of them had a cytogenetically normal pattern at diagnosis. In four of ten relapsed ALL cases chromosomes analyses were available. A relapse in donor cells and a hyperdiploid pattern were observed in two cases, respectively, while a normal, recipient pattern was documented in the other two cases. Serial chromosome studies performed in acute leukemia patients after bone marrow transplantation may allow the detection of different chromosomal patterns of relapse. In those cases who relapsed with a cell clone cytogenetically different from the pattern at diagnosis, a direct role played by the conditioning treatment in the pathogenesis of the relapsing disease may be hypothesized.

Acute Disease↗
PubMed1987

Cytogenetic analyses in 89 patients with secondary hematologic disorders--results of a cooperative study.

Eighty-nine patients who developed a secondary hematologic disorder and were studied with chromosome analysis were collected from nine institutions. The results of the study confirmed previous findings, in particular, -5/5q-, -7/7q-, -17, and +21 were the most frequently encountered aberrations. Moreover, a t(1;7)(p11;p11) was reported in four cases and consistent chromosome abnormalities were observed in a small group of patients who had been treated only with surgery, but not with chemo- or radiotherapy for a previous tumor.

Acute Disease↗
PubMed1987

Evidence for the involvement of host-derived OKT8-positive T cells in the rejection of T-depleted, HLA-identical bone marrow grafts.

The recent introduction of a variety of techniques for removing T cells from bone marrow grafts has reduced the incidence of graft-versus-host disease (GVHD)-associated morbidity and mortality. Whether this advance will be translated into improved patient survival is unclear at present, mainly because these procedures increase the risk of graft failure. Since 1983 we have transplanted 25 consecutive leukemia patients with HLA-identical sibling grafts purged of T cells by a single incubation with the monoclonal antibody Campath-1 and donor complement. This approach was successful in reducing T cell contamination of the graft and preventing acute and chronic GVHD. In this group of patients two suffered irreversible graft failure and one developed reversible graft failure. In a similarly sized group of patients previously transplanted with unpurged marrow according to the Seattle protocol, no episodes of graft failure occurred. Since other causes of graft failure, such as drug toxicity or viral infections, could be largely excluded, this suggested that the graft failures were specifically related to the purging process. In haploidentical bone marrow transplantation (BMT) O'Reilly has identified residual host-versus-graft activity (HVG) as a cause of graft failure. The causes and mechanisms of graft failure in T-depleted HLA-identical sibling transplants have not been extensively investigated to date. In the three graft failures observed by us, the loss of the graft was preceded by the appearance of a population of activated lymphocytes. We have determined the phenotype and origin of this population and investigated its interactions with donor hemopoietic tissue in vitro.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Mimicking anti-S simulating a delayed transfusion reaction.

An autoantibody mimicking anti-S specificity is described in an S-s+ patient. The antibody was detected 2 weeks after transfusion. The direct antiglobulin test (DAT) was positive and the antibody was thought to be an alloantibody formed after the transfusion. Eighteen months later, the DAT was still positive and anti-S could be eluted from the patient's red blood cells in spite of the fact that these were S-s+. The autoantibody was characterized as mimicking anti-S specificity by in vitro absorption studies. It was present during the 3 years in which the patient was observed without causing hemolitic anemia.

Aged↗