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  • 1
    ISSN: 1432-1084
    Keywords: Heart ; Lung ; Nodule ; Lymphoma ; CT ; Transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Posttransplant lymphoproliferative disorders (PTLD), developing after immunosuppressive therapy in human organ-graft recipients, are, for the most part, Epstein-Barr virus-induced. The earlier the diagnosis is made, the greater the potential for reversibility. The chest radiographs and CT scans of 10 patients with thoracic locations of PTLD were reviewed. Mediastinal (n = 3) and hilar adenopathy (n = 2), pulmonary nodules (n = 8), and pleural thickening or effusion (n = 4) were encountered. The incidence of partial resolution with clinical remission (n = 4) appears to be noteworthy, and in all likelihood is related to the extensive necrosis (n = 5) that is frequently seen. Slow regression, transitory deterioration in one case, and localization only on the graft side in two cases, were observed. These morphological and evolutionary peculiarities must be known in order to optimize the diagnosis, and thus the prognosis, of these very original disorders.
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  • 2
    ISSN: 1279-8509
    Keywords: Acute myeloid leukemia ; Therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p 〈 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.
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  • 3
    ISSN: 1279-8509
    Keywords: T cell reconstitution ; Bone marrow transplantation ; Hematopoietic stem cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hematopoietic stem cell (HSC) transplantation, whatever its conditions, is associated with an increased risk of infections and tumoral complications, because of a delayed immune reconstitution. T-cell regeneration has been mostly investigated and appears to come more from graft and/or host mature T-cells, rather than from the differentiation/maturation of reinfused progenitors. In allogeneic setting, the immune defect is enhanced by the immune host/donor conflict and the use of prophylactic or curative immunosuppressive therapy. The tools used for studying post-transplant immunity are the following: immunophenotyping (kinetics and alterations of lymphocyte subset reconstitution), functional studies of T cell proliferation, cytokine production, cytotoxicity and signal transduction, as well as studies of T cell repertoire diversity. The CD4/CD8 cell immunophenotyping might be enough for routine clinical evaluation, allowing an adapted prophylaxis of opportunistic infections in those immune-suppressed patients, while functional assays might be useful to evaluate the persistence overtime of defects in immune reconstitution. These overall assays are useful both for basic and clinical research and allow better understanding in the mechanisms for T cell regeneration in the diverse types of HSC transplants performed nowadays particularly after graft of purified HSC where immune reconstitution remains a key question.
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  • 4
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Lymphoid neoplasia is now well known to occur in patients with human immunodeficiency virus (HIV) infection but the first case of acute monocytic leukaemia in an HIV-seropositive man has been only recently described. We report the case of an HIV-infected patient who simultaneously developed skin lesions of acute monocytic leukaemia and chicken pox. We suggest that HIV may produce a malignant transformation of monocytic cells.
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  • 5
    ISSN: 1279-8509
    Keywords: CLL Fludarabine ; Neurologic complications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since 1990 we have treated 60 patients with standard-dose fludarabine for chronic lymphocytic leukemia (B-CLL), on a compassionate basis. Three patients developed grade IV neurologic complications after treatment, with demyelination of white matter on magnetic resonance imaging (MRI) in patient # 1, diffuse demyelination, abnormal oligodendroglia and enlarged astrocytes at brain biopsy in patient n°2, and progressive multifocal leukoencephalitis (PML) with JC virus on brain biopsy in patient # 3. The neurotoxicity of fludarabine was often observed after administration of high doses (90-120 mg/m2). At standard doses (18-25 mg/m2) neurologic complications were observed in very few cases (0.2%). PML was observed in only 0.52% of patients with chronic lymphocytic leukemia (CLL), particularly those with advanced CLL. Our findings are consistent with the results of published studies and show an increase in neurologic complications in patients with advanced CLL treated with fludarabine. This increased vulnerability is probably multifactorial, but may be secondary to the immunodeficiency.
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  • 6
    ISSN: 1279-8509
    Keywords: SCID mice ; Immunological disorders ; Hematological disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mice homozygous for a SCID mutation (SCID mice) are severely deficient in T and B lymphocytes. The absence of effector T and B cells has encouraged investigators to attempt engraftement of SCID mice with human fetal tissues, mature lymphocytes, hematopoietic progenitors and tumors. SCID mice can be reconstituted with human lymphocytes and are of interest for studying normal and abnormal lymphocyte development and function. SCID mice are also providing an in vivo model of infectious diseases. In addition, SCID mice readily support normal and pathologic human hematopoiesis differentiation and is useful for testing innovative hematological disease therapy. SCID mice with a fully functionnal human immune or hematopoietic system therefore seem to be extremely valuable for biomedical research.
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  • 7
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; Hodgkin's disease ; relapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Despite high-dose therapy and ASCT some patients with aggressive HD fail to achieve long-term survival. Patients and methods: Forty-three patients with induction failure (n = 19) or very unfavorable (UF) relapse (n = 24) from HD were included in a multicentric study of tandem ASCT. They planned to receive two courses of IVA75 with GCSF and blood stem-cell collection. ASCT1 was conditionned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2, melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg). After salvage therapy, response 〉50% was observed in 63% of the patients (six patients were included for refractory relapse). Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT. Results: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen. Two VOD with one fatal occured with busulfan at 16 mg/kg and one hemorragic cystis, no further grade 4 toxicity was observed with the reduced doses of busulfan (12 mg/kg). After ASCT2, 83% of these UF patients were in remission and 20% relapsed within the first year. On an intent-to-treat analysis, 22 of 43 patients are in continuous CR (including 8 patients with induction failure). For the whole population (n = 43) and for patients receiving the two ASCT (n = 32), the two-year survival from the date of progression were respectively at 65% and at 74%. Conclusion: double ASCT is feasible in very UF relapse from HD and may lead to some prolonged remission.
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  • 8
    ISSN: 1569-8041
    Keywords: chimeric anti-CD20 monoclonal antibody ; disorder ; post transplant B lymphoproliferative
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:B-lymphoproliferative post-transplant disorder (BLPD)is a severe complication of organ and bone marrow transplantation. Thereduction of immuno-suppressive therapy or surgery for localized disease maycure some BLPDs. Other therapeutic approaches such as chemotherapy andantiviral drugs are toxic and of limited efficacy. Adoptive immunotherapy withdonor T-cell infusions has yielded promising results but is, at the presenttime, easily applicable only in bone marrow-transplanted patients. Anti-B-cellMurine monoclonal antibodies (MoAbs) have proven effective but are no longeravailable for human use. We report the activity of a humanized anti CD 20 MoAb (Rituximab–MABTHERA® Roche) in 32 episodes of BLPD treated in 14French centers. Patients and methods:Between November 1997 and September 1998,32 patients were diagnosed with BLPD. Twenty-six patients had undergone solidorgan transplants (liver 8, kidney 8, heart 4, lung 3, heart lung 1,kidney-pancreas 1, liver-kidney 1) and six patients had received bone marrowtransplantations. The median age of the patients was 34 years (3–67years) and the median delay between graft and tumor 5 months (1–156months). In organ recipients, tumors were classified as polymorphic andmonomorphic in 10 and 15 cases, respectively; 4 of 6 bone marrow transplantrecipients were treated without pathology documentation because of a rise inEBV load, fever and lymph node enlargement. Tumors were associated with EBVin 22 of 26 tested cases. Rituximab was used as first-line therapy in 30patients (after reduction of immunosuppressive treatment in 27 patients) andas salvage therapy in 2 patients (after failure of chemotherapy). The mediantime from diagnosis of BLPD to treatment with Rituximab was 14 days(1–110 days). Two patients received eight infusions, twenty-six patientsfour infusions, one patient three infusions and three patients two infusionsof 375 mg/m2. Results:The tolerance of rituximab was good. The overall responserate was 69%, with 20 complete responses and 2 partial responses. Insolid organ transplant the response rate was 65% (15 CR and 2 PR) whileit was 83% in bone marrow-transplanted patients (5 CR). With a medianfollow-up of 8 months (1–16 months) 24 patients are still alive. Theone-year projected survival is 73%. Of the 22 patients who achievedresponse, 15 patients (11 solid organ transplant and 4 bone marrow transplant)are alive with no evidence of disease, 4 patients relapsed a median of 7months (3–10 months) after treatment and 3 died while in CR ofconcurrent diseases. Of the 10 patients who did not respond to Rituximab 5 arealive with no evidence of disease after salvage therapy. Conclusions:The use of rituximab appears to be a safe andrelatively efficient therapy in BLPDs. The results need to be confirmed in aprospective multicentric trial.
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  • 9
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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