A syndrome of idiopathic intrahepatic cholestasis occurs in some patients with Hodgkin's lymphoma. The underlying mechanism is poorly understood. In this paper we describe three patients with Hodgkin's lymphoma in whom severe intrahepatic cholestasis of unknown pathogenesis developed. In two cases jaundice was the presenting symptom; all three patients died with intractable liver damage. The three patients were initially thought to have idiopathic Hodgkin's-associated cholestasis, but subsequent review of histological material revealed advanced vanishing bile duct syndrome in addition to severe cholestasis. Ten liver specimens were obtained from 4 to 97 wk after the onset of jaundice (seven needle biopsies, one wedge biopsy, two postmortem livers). In seven liver specimens taken within 30 wk of the onset of jaundice, portal tracts characteristically had a "burned-out" appearance without secondary periportal changes related to chronic cholestasis. Three biopsy specimens obtained from one of the patients more than 1 yr after the onset of jaundice showed evidence of progressive periportal damage in the form of fibrous expansion, marginal ductular proliferation and copper-associated protein deposition. More than 80% of small portal tracts lacked recognizable bile ducts in the final liver specimens obtained from the three patients. These observations suggest that Hodgkin's lymphoma should be included in the list of diseases associated with loss of intrahepatic bile ducts. The possibility of a vanishing bile duct syndrome should be considered in the differential diagnosis of unexplained intrahepatic cholestasis in patients with Hodgkin's disease.
Summary:logous rescue following myeloablative therapy. 1 In this context, PBSC can be successfully mobilised with chemotherapy in combination with granulocyte colony-stimulatWe have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLAing factor (G-CSF) or with G-CSF alone. 2 Reports of the first allogeneic PBSC transplants (PBSCT) showed that matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of PBSC could be safely mobilised from normal donors using G-CSF alone and could achieve trilineage engraftment in GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disthe recipients, without severe graft versus-host-disease (GVHD). 3,4 The feasibility of this approach has recently ease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), been confirmed in several reported series of patients undergoing allogeneic PBSCT. [5][6][7][8] In these reports large cyclosporin A alone (n = 2) or cyclosporin A and methylprednisolone (n = 1). Stem cells were mobilised using numbers of CD34 + cells were successfully collected from donors following administration of G-CSF and the data G-CSF, collecting a median of 5.75 × 10 6 CD34 + cells/kg recipient weight (range 0.94-35 × 10 6 CD34 + cells/kg).confirmed that blood stem cells resulted in long-term haemopoietic engraftment following transplantation. They Engraftment times to a neutrophil count Ͼ0.5 × 10 9 /l and platelets Ͼ20 × 10 9 /l were achieved at a median of also suggested that there may be advantages over allogeneic bone marrow transplantation (BMT) in terms of faster day +14 (range 10-25) and day + 14 (range 9-130) respectively. Patients receiving у4 × 10 6 CD34 + cells/kg haemopoietic engraftment, as is the case in autologous transplantation, 9 however, the number of CD34 + cells had significantly accelerated neutrophil and platelet engraftment and this number of CD34 + cells would required for optimal engraftment is still not certain. Allogeneic PBSCT have been performed in the United appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluKingdom (UK) since 1993. To obtain an overview of this activity we surveyed 20 BMT units in the UK and report an able patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in analysis of 44 patients, from nine centres, where allogeneic transplantation using PBSC from related donors had been 17 out of 36 evaluable patients, there was no significant difference between the standard-and poor-risk groups undertaken between March 1993 and March 1996, specifically looking at engraftment kinetics and the incidence of in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using acute and chronic GVHD. PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further eviden...
Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.
Summary Acute myeloid leukaemia (AML) causes life‐threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two‐thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti‐AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high‐risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22–30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML.
Summary.The results for colony forming unit granulocytemacrophage (CFU-GM) assays vary substantially between centres. It is possible that colony counting is largely responsible for this discrepancy. In order to examine this exclusively from the many factors that make up the CFU-GM assay, we performed a colony counting exercise involving 11 laboratories. Two-way analysis of variance showed a highly significant difference (P ¼ 0 : 0001) in the counts obtained from the centres. One centre was found to score consistently high and two others scored consistently low numbers of colonies. This suggests that identification of colonies is a major source of variation between centres.
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