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Biomedical subjects

R Bassan

Publications and source records attributed to R Bassan.

At least 91 records · Page 5Linked to original sources
PubMed1989

Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells.

Clinical and laboratory findings of B-cell immune dysfunction were evaluated in ten patients with a large granular lymphocyte/natural killer cell proliferative disease (LGL/NK-PD). Increased immunoglobulin synthesis with autoantibody formation was documented: polyclonal hypergammaglobulinaemia (six patients), neutrophil autoantibody (one patient), antinuclear antibody (one patient), and rheumatoid factor (five patients). In addition, serum beta 2-microglobulin level was raised in seven patients, a benign monoclonal gammopathy was detected in one, and concurrent B-type hairy cell leukemia in another. Most patients experienced the complications of hemocytopenia, polyarthritis or rheumatoid arthritis, and immediate allergic reactions to drugs or environmental substances, rather than from symptoms of progressive LGL/NK-PD. A review of the literature confirms that an increased immunoglobulin production is common in LGL/NK-PD, and that patients are likely to develop multiple autoantibodies. The incapacity of proliferating, abnormal LGL/NK cells to suppress B-cell activation and immunoglobulin synthesis, documented by several in vitro studies, offers a pathogenetic explanation for these phenomena. This study shows that an anomalous B-cell function contributes greatly to the morbidity of disease in LGL/NK-PD, and points out the utility of investigating the LGL/NK cell system in patients with autoimmune pathologic characteristics of unclear origin.

Adult↗
PubMed1989

Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis.

We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease.

Adolescent↗
PubMed1989

Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia.

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.

Animals↗
PubMed1989

Differences in the expression of alkaline phosphatase mRNA in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria polymorphonuclear leukocytes.

Paroxysmal nocturnal hemoglobinuria (PNH) and the stable phase of chronic myelogenous leukemia (CML) are the two hematological conditions known to be associated with low levels of leukocyte alkaline phosphatase (LAP) activity in peripheral blood polymorphonuclear cells (PMN). LAP mRNA levels were determined in PMN from PNH and CML patients by RNA blotting analysis. In CML, LAP mRNA is undetectable, suggesting either decreased transcription or rapid degradation of the message. Contrarily, in PNH normal or high levels of LAP mRNA are present. This latter finding supports the concept of a deficit in the anchorage of the protein to the plasma membrane through the glycolipid pathway, even though other post-transcriptional mechanisms could be involved.

Alkaline Phosphatase↗
PubMed1988

Association of large granular lymphocyte/natural killer cell proliferative disease and second hematologic malignancy.

We describe the first three patients with a large granular lymphocytosis/lymphocytic leukemia and another blood malignancy. In two, a myeloproliferative disorder developed soon after the diagnosis of abnormal proliferation of large granular lymphocytes-natural killer (LGL-NK) cells, a myelodysplastic syndrome evolving to acute leukemia and a Philadelphia-positive chronic myelogenous leukemia. In these cases, LGLs expressed the phenotype of CD3+ NK and CD3- NK cells, respectively, and were clonal in the first patient as demonstrated by T-cell receptor gene rearrangement study. In the third case, a similarly clonal excess of LGLs, phenotypically CD3+ NK cells, was detected following a diagnosis of B-cell hairy-cell leukemia. Clinically, the concurrence of LGL proliferation and other leukemia did not seem to confer a worse prognosis on the patients. Although an association by chance remains a possible explanation, a common origin from an altered precursor cell for both myeloid and LGL proliferations in the first two cases is discussed, whereas in the third it might be related to the severe immune derangement frequently observed in hairy-cell leukemia.

Adult↗
PubMed1988

Therapeutic efficacy of danazol in myelodysplastic syndromes.

Sixteen unselected untreated patients with primary myelodysplastic syndromes (MDS) and various combinations of blood cytopenia were treated with danazol, an attenuated androgen reported to be of some value in these conditions. After a 12 week trial (danazol 600 mg/day/p.o.), anaemia improved in 4/14 patients, with transfusional requirements being reduced by 50% or more in four other cases (response 57%). An enhanced reticulocyte production was documented in 6/13 cases (46%), and thrombocytopenia resolved in 5/8 (62%). Results of the granulocyte count were less satisfactory, with only one partial response obtained among five cases. A normalization of the monocyte count was seen in 3/5 patients with chronic myelomonocytic leukaemia, with one of them achieving a complete haematological and clinical remission lasting 6 months. Circulating blast cells decreased significantly (50% or more) in 4/6 cases. Although clinical symptoms from anaemia and bleeding disappeared in responsive cases, four patients developed acute non-lymphocytic leukaemia. Danazol was well tolerated and produced no acute or chronic toxicity. The drug appears useful in the management of anaemic and thrombocytopenic MDS patients.

Aged↗
PubMed1988

Investigation of chronic lymphocytosis in adults.

Thirteen cases of idiopathic chronic lymphocytosis are the subject of this report. Patients showed a lymphocyte count between 4 and 15 X 10(9)/L for at least six months, marrow lymphocytosis not exceeding 25%, absence of lymphomegaly and hepatosplenomegaly, and no associated infections, immune, or neoplastic disease. Morphologic examination of smears revealed a lymphocytosis of large granular lymphocytes in five. A selected battery of polyclonal and monoclonal antisera to antigens commonly found on B-, T-, and natural killer cells allowed the identification of six cases of early B-cell chronic lymphocytic leukemia, two cases of T-cell lymphocytosis with a suppressor or helper T-cell phenotype, and five cases of large granular lymphocyte/natural killer cell proliferative disease. The results demonstrate the usefulness of combining morphologic and phenotype studies for the investigation of chronic lymphocytosis, which often appears as an early leukemia or a benign clonal proliferative disorder of lymphocyte subsets.

Adult↗
PubMed1988

Short-term therapy for acute myelogenous leukemia.

Since 1978, 187 patients (age range, 15 to 59, median 44 years) have received short-term chemotherapy as part of three sequential open studies (B-IX, X, Xb) or a randomized clinical trial (B-XI). An intended six cycles of Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), cytarabine (ara-C), and thioguanine (TG) were administered with as short an intercycle time as possible. No further therapy was administered. Complete remission (CR) was achieved in 118 of 187 patients (63%). On univariate and multivariate analyses achievement of CR correlated adversely with a low serum albumin at presentation and an antecedent marrow disorder. Forty-five patients continue in first remission between 15 months and 8 1/2 years, no relapses being seen after 3 1/2 years (median follow-up, 3 1/2 years). The median duration of remission was 1 year. M3 morphology, a blast count less than 100 x 10(9)/L, and absence of hepatosplenomegaly correlated favorably with remission duration. There was no difference in duration of remission between patients receiving 3, 4, 5, or 6 cycles. The best results overall were achieved in patients under the age of 40, with 43% projected to remain free of disease at 5 years. Fifty patients remain alive between 17 months and 9 years, the predicted actuarial survival being 25% at 5 years.

Actuarial Analysis↗
PubMed1987

Treatment of the lymphoid blast crisis of chronic myeloid leukemia.

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.

Adult↗