Non-B, non-T acute lymphoblastic leukaemia terminating in malignant histiocytosis: a new case and a review of the literature.
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Biomedical subjects
Publications and source records attributed to A Tabilio.
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Staphylococcal protein A conjugated to horseradish peroxidase was employed in an indirect immuno-staining technique to identify intracellular antigens in paraffin-embedded tissues. The sections were incubated with specific antisera and the antigen-IgG complexes demonstrated with protein A-peroxidase conjugate. Immunoglobulins, lysozyme and insulin were satisfactorily detected by this technique. A comparison of this method with the PAP, "labelled antigen" and peroxidase-labelled antibody sandwich techniques was made.
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Ultrastructural characterization and localization of intracellular immunoglobulin in peripheral blood mononuclear cells from a patient with hairy cell leukemia were studied by the direct immunoperoxidase technique. Approximately 20--30% of hairy cells stained positive for gamma-heavy and K-light chains, and this staining was limited to certain rough endoplasmic reticulum profiles. These ultrastructural findings can be considered an additional argument for the B cell origin of hairy cells.
T cell-depleted allogeneic stem cell transplantation is associated with delayed immunological reconstitution. Bone marrow stroma and interleukin 7 (IL-7) regulate homeostasis of T lymphocytes. We engineered human stromal cells with a retroviral vector containing the IL-7 gene and studied in vitro effects on T cells. Human stromal cells were successfully transduced and generated a layer that was morphologically and phenotypically normal. IL-7-engineered stromal cells conserve the biological properties of unmanipulated stromal cells. Through their production of IL-7, they enhance survival and homeostatic proliferation of naive T cells. Because of this cytokine production, they might be an ideal vehicle for gene therapy aimed at supporting lymphopoiesis in the T cell-deficient host.
BACKGROUND: Although imatinib is the standard treatment for chronic myeloid leukaemia, not all patients reach complete cytogenetic remission (CCR) and most maintain detectable disease at the molecular level. We investigated whether a vaccine targeting the BCR-ABL-derived p210 fusion protein was an active and specific immunotherapy. METHODS: We recruited 16 patients who had chronic myeloid leukaemia (with the b3a2 fusion point of p210), stable residual disease, a minimum treatment of 12 months of imatinib or 24 months of interferon alfa, and no further reduction of residual disease for at least 6 months preceding enrollment. They were given six vaccinations with a peptide vaccine derived from the sequence p210-b3a2 plus molgramostim and QS-21 as adjuvants (CMLVAX100) before assessment of immunological and disease response, which included detecting amounts of b3a2 transcripts by standardised quantitative real-time reverse-transcriptase PCR. RESULTS: Of ten patients on imatinib, nine started CMLVAX100 having had a median of 10 months' stable cytogenetic disease (median 10% Philadelphia-chromosome-positive metaphases), whereas one started in stable CCR. All patients' cytogenetic responses improved after six vaccinations, with five reaching CCR. Notably, three of these five patients also had undetectable amounts of b3a2 transcript (BCR-ABL:beta2 microglobulin ratio <0.00001). Six patients on interferon alfa treatment with a median of 17 months' stable residual disease (median 13% Philadelphia-chromosome-positive cells) were also vaccinated. All but one had improved cytogenetic responses, and two reached CCR. Overall, we recorded peptide-specific delayed-type hypersensitivity (in 11 of 16 patients), CD4 cell proliferation (13 of 14 assessed), and interferon gamma production (five of five assessed). INTERPRETATION: Addition of CMLVAX100 to conventional treatment in patients with chronic myeloid leukaemia might favour further reduction of residual disease and increase the number of patients reaching a molecular response.
AIMS AND BACKGROUND: To investigate the safety and efficacy of a high-dose chemotherapy regimen with etoposide, carboplatin and thiotepa in high-risk stage II-IIIA breast cancer and in responsive metastatic patients. STUDY DESIGN: From April 1992 to December 1998, 24 patients with high-risk stage II-IIIA breast cancer (> or = 9 positive nodes) and 9 responsive metastatic patients were enrolled in the trial. After induction chemotherapy with an anthracycline-based regimen, peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (5-16 microg/kg/s.c./day). The high-dose chemotherapy regimen consisted of etoposide (1000 mg/m2), carboplatin (800 mg/m2) and thiotepa (500 mg/m2). At the end of the high-dose chemotherapy, all stage II-IIIA patients received radiotherapy to the breast or chest wall and draining nodes; stage IV patients were irradiated to sites of disease, if feasible. All ER+ and/or PgR+ patients were treated with hormone therapy. RESULTS: For stage II-IIIA high-risk patients, the median follow-up was 4.36 years (range, 1.93-6.94), and the Kaplan-Meier estimate at 5 years of disease-free survival and overall survival was 54.8 +/- 11% SE and 76.73 +/- 9.4% SE, respectively. For metastatic patients, the median follow-up was 4.93 years (range, 4.15-7.95), and the Kaplan-Meier estimate at 5 years of progression-free survival and overall survival was 22.2 +/- 13.9% SE and 76.2 +/- 14.8% SE, respectively. No treatment-related deaths were observed. CONCLUSIONS: Our results are comparable to those obtained in other high-dose chemotherapy trials but do not seem to be superior to conventional-dose therapy given to similar patients.
BACKGROUND: Chronic myeloid leukemia arises from a somatic mutation in a pluripotent stem cell. It generally terminates with a blastic crisis (BC). One third of BC are lymphoid, and most have a pre-B phenotype. Few cases of T-lymphoid BC have been reported. Here we describe a lymph node blast crisis mimicking T-immunoblastic lymphoma. METHODS: Bone marrow and lymph nodes were histologically examined by standard methods and by an immunoperoxidase technique. Cytogenetic studies were also performed on lymph node and blood cells. Analysis of T-cell receptor genes and BCR rearrangements were performed on DNA extracted from both frozen bone marrow and lymph-node cells. RESULTS: Lymph-node histology showed an infiltration by large lymphoid blasts, consistent with a diagnosis of immunoblastic lymphoma. Blast cells were CD2, CD7, TDT positive, and negative for myeloid and mature lymphoid antigens. The Ph1 chromosome was found in both bone marrow and lymph-node cells. BCR rearrangement was found in the DNA from both bone marrow and lymph-node cells. TCR genes were not rearranged. DISCUSSION: The present study provides strong evidence that the lymph-node blast crisis of CML can assume the morphological appearance of immunoblastic lymphoma and may retain the immunological phenotype and genetic features of early T cells with BCR rearrangements.
A group of polypeptide factors that regulate cell growth and differentiation has been tested for their biological activities on the growth and differentiation of leukemic cells isolated from patients with Acute Myeloid Leukemias (AML). The effects of Transforming Growth Factor beta 1 (TGF beta), Tumor Necrosis Factor alpha (TNF alpha), Interferon gamma (IFN gamma) and LIF-HILDA were compared on leukemic cells cultured in vitro for seven days. Spontaneously growing leukemic cells were selected in order to study either inhibition or enhancement of proliferation induced by these factors. Only TGF beta 1 was found to induce a clear inhibition of leukemic proliferation in all cases tested. Recombinant TNF alpha and IFN gamma were found to induce either inhibition or enhancement of the proliferation on separate specimens. Under the conditions of culture, it was not possible to document any effect of LIF-HILDA. Cell differentiation and cell maturation were documented studying the modulation of cell surface antigens. TGF beta did not modify antigen expression on the cells surviving after 3 days in culture. Both TNF alpha and IFN gamma were found to enhance the expression of adhesion molecules and to a lesser extent, the expression of some lineage associated antigens. No effect of LIF-HILDA on antigen modulation was documented in the cases tested. These data confirm that TGF beta is by itself a potent inhibitor of the myeloid leukemia cells proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Extramedullary blast crisis (EBC) with T-lymphoid phenotype has been reported rarely and generally associated with extremely poor prognosis. We describe a case of T-lymphoid EBC in which long-lasting remission was observed following intensive chemotherapy and allogeneic bone marrow transplantation (BMT). Characterization of bone marrow (BM) and lymph node (LN) cells was performed by means of morpho-cytochemical, cytogenetic, immunophenotypic and molecular analyses. These showed, together with a marrow picture consistent with typical Ph'+ chronic myelogenous leukemia, the expansion of an early T-lymphoid (CD7+/TdT+) LN cell population exhibiting the same bcr rearranged pattern and an additional Ph' chromosome. At the present time, 33 months after BMT, the patient is alive and well, with persistent clinical, hematological, cytogenetic and molecular evidence of complete remission.
In an attempt to reduce the risk of leukemic relapse, different post-remission intensifications based on high-dose Ara-C (HiDAC) and autologous bone marrow transplantation (ABMT) were evaluated in patients with acute non lymphocytic leukemia in first remission and compared as to response and toxicity. Between September, 1985 and May, 1987, 34 patients in complete remission were eligible for our study. Induction therapy consisted of one or two courses of daunorubicin (DNR) and Ara-C (schedule 3 + 7). Fourteen patients receiving intensive post-remission chemotherapy with DNR + Ara-C (schedule 2 + 5), HiDAC + DNR, and ABMT following pretransplant BAVC conditioning entered the first pilot study. A high toxicity was observed and only 5 of them completed the full treatment plan. Thus the second pilot study used a single post-remission intensive course with HiDAC + m-AMSA and ABMT following cyclophosphamide plus TBI or BAVC. This approach was more feasible. The preliminary results show the usefulness of intensive post-remission therapy: in fact, all patients but one who completed the treatment program are still in continuous complete remission. A large number of patients and a longer follow-up are required to draw final conclusions.
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Diabetes insipidus and thrombocytosis were presenting symptoms in a case of adult ANLL-M1. Cytogenetic investigations revealed a typical 3q rearrangement, i.e. inv(3)(q21q26). A subclone with monosomy 7 was also found and documented by FISH analysis. Correlations between clinical/hematological features and cytogenetic/FISH results are discussed.