1/80. Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity. iron overload may induce liver toxicity after hematopoietic stem cell transplantation (HSCT), but it is not known if iron depletion prior to HSCT can reduce the risk of severe toxicity in this setting. We used subcutaneous recombinant erythropoietin (EPO) (25 UI/kg) three times a week and phlebotomy once a week, to prevent liver toxicity in a patient with advanced acute leukemia and liver disease due to severe iron overload, previous drug toxicity and hepatitis c viral infection. Over the 9 months prior to allogeneic HSCT, 34 phlebotomies were carried out. serum ferritin dropped from 2964 to 239 microg/l and the ALT dropped to near normal values. At allogeneic HSCT no liver toxicity was observed, suggesting that iron depletion in the pretransplant period may contribute to reducing transplant-related toxicity in selected cases. ( info) |
2/80. Premalignant lesions and hepatocellular carcinoma in a non-cirrhotic alcoholic patient with iron overload and normal transferrin saturation. A 66-year-old white man had a hepatic resection for a 6-cm well-differentiated hepatocellular carcinoma which had developed in a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking and heterozygosity for the C282Y mutation of the HFE gene. The liver was mildly fibrotic and overloaded with iron. It also contained numerous iron-free hepatocellular lesions from <1 to 10 mm, suggesting a premalignant change. These lesions were of three types: (i) iron-free foci, (ii) hyperplastic nodules and (iii) dysplastic nodules with severe dysplasia or even foci of well-differentiated grade I hepatocellular carcinoma. This observation suggests the possibility of malignant transformation of the liver in the newly-described syndrome of iron overload and normal transferrin saturation. It also illustrates the multistep process of carcinogenesis in the non-cirrhotic liver. ( info) |
3/80. mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. In a 10-year consecutive series of 263 allogeneic bone marrow transplant recipients, we identified five cases (1.9%) of invasive mucormycosis. Only one infection occurred within the first 100 days after transplantation, while the remainder complicated the late post-transplant course (median day of diagnosis: 343). Sites of infection were considered 'non-classical' and included pulmonary, cutaneous and gastric involvement. No case of fungal dissemination was observed. mucormycosis was the primary cause of death in three of the five patients. Corticosteroid-treated graft-versus-host disease, either acute or chronic, or severe neutropenia were present in all cases. However, compared with a matched control population, the most striking finding was the demonstration of severe iron overload in each of the mucormycosis patients. The mean level of serum ferritin, transferrin saturation and number of transfused units of red cells (2029 microg/l, 92% and 52 units, respectively) in the study group is significantly higher compared with the control group (P < 0.05). The difference with other risk groups for mucormycosis, including deferoxamine-treated dialysis patients and acidotic diabetics, was analyzed in view of the possible pathogenic role of iron. Although these infections are often fatal, limited disease may have a better prognosis if diagnosed early and treated aggressively. ( info) |
4/80. Management of porphyria cutanea tarda in the setting of chronic renal failure: a case report and review. The treatment of porphyria cutanea tarda (PCT) in patients with chronic renal failure poses a therapeutic challenge. In the absence of renal failure, phlebotomy and oral antimalarials have been the standard of care for PCT. However, in the presence of renal failure, associated chronic anemia often precludes the use of phlebotomy, and oral antimalarials are usually ineffective. We describe a patient with severe symptomatic PCT and chronic renal failure whose disease was successfully managed with a combination of high-dose erythropoietin and small volume phlebotomy. We also review several previously reported approaches to management of PCT in the setting of renal failure, which include small repeated phlebotomy, erythropoietin, deferoxamine, chloroquine, plasma exchange, high-efficiency/high-flux hemodialysis, cholestyramine, charcoal hemoperfusion, and kidney transplantation. An algorithm for the management of these patients is proposed. ( info) |
5/80. Regression of multiple hepatic masses in a young patient with thalassaemia. BACKGROUND: We report a young girl with thalassaemia who showed development and regression of multiple hepatic masses. RESULTS: The tumours, detected 3 years after allogeneic bone-marrow transplantation, showed progressive reduction in size and number following a phlebotomy program to treat iron overload. CONCLUSION: The detailed CT, MRI and histological findings are described. ( info) |
6/80. Primary pseudomonas meningitis in an adult, splenectomized, multitransfused thalassaemia major patient. A 19-year-old splenectomized, multitransfused female patient with beta-thalassaemia major developed primary meningitis due to P. putida. Her blood cultures were negative. P. putida is an unusual nosocomial organism to cause primary meningitis. infection due to this organism carries high mortality. However, owing to early diagnosis and energetic treatment this patient survived without any sequelae. A review of serious infections over the last 7 years in patients in our thalassaemia care centre revealed 11 serious infections among our splenectomized patients (n = 46) and none in the non-splenectomized group (n = 106). Surprisingly, all overwhelming infections (23.8% in the splenectomized group) were caused by Gram-negative bacilli like klebsiella, pseudomonas, aeromonas and campylobacter species. As all our splenectomized patients had prior pneumococcal vaccination and oral penicillin prophylaxis, overwhelming septicaemia due to S. Pneumoniae was successfully prevented, but an increasing incidence of overwhelming sepsis due to Gram-negative bacilli, against which no vaccination or suitable prophylactic antibiotics are available, is now posing a new threat to this vulnerable group of patients. ( info) |
7/80. Severe congenital dyserythropoietic anaemia type I: prenatal management, transfusion support and alpha-interferon therapy. We report a case of congenital dyserythropoietic anaemia, type I, with severe pre- and postnatal manifestations. Exchange transfusions were required for fetal anaemia (3.5 g/dl) at 28 and 30 weeks of gestation. Transfusions were administered at birth (Caesarean section at week 35) and at regular intervals thereafter. At 14 months, alpha-interferon therapy was initiated (106 units three times a week). This resulted in stabilization of the haemoglobin at or above 11 g/dl and a reduction in the percentage of erythroblasts with ultrastructurally abnormal heterochromatin. After 9 months, the dose of alpha-interferon was decreased to 106 units twice a week. No relapse of anaemia was noted during an additional 4 months of follow-up. ( info) |
8/80. Hereditary hemochromatosis in a patient with congenital dyserythropoietic anemia. Herein is described the case of a young woman presenting with iron overload and macrocytosis. The initial diagnosis was hereditary hemochromatosis. Severe anemia developed after a few phlebotomies, and she was also found to have congenital dyserythropoietic anemia that, though not completely typical, resembled type II. Only genetic testing allowed the definition of the coexistence of the 2 diseases, both responsible for the iron overload. This report points out the need to consider congenital dyserythropoietic anemia in patients with hemochromatosis and unexplained macrocytosis and, conversely, to check for the presence of hereditary hemochromatosis in patients with congenital dyserythropoietic anemia and severe iron overload. To the authors' knowledge, this is the first report of homozygosity for the C282Y mutation of the HFE gene in a patient affected by congenital dyserythropoietic anemia. ( info) |
9/80. Hepatic iron overload in aceruloplasminaemia. We report the case of a 52 year old male with diabetes mellitus and long standing evidence of hepatic iron excess. Initially considered to have haemochromatosis, this patient was reevaluated when hepatic iron stores were found to be unaffected by a prolonged course of weekly phlebotomy. The development of neurological disease prompted diagnostic consideration of aceruloplasminaemia, which we confirmed by demonstration of a novel frameshift mutation in the ceruloplasmin gene. Our inability to resolve the patient's iron overload by regular phlebotomy is consistent with recent animal studies indicating an essential role for ceruloplasmin in cellular iron efflux. Evaluation of this case underscores the clinical relevance of aceruloplasminaemia in the differential diagnosis of hepatic iron overload and provides insight into the pathogenetic mechanisms of hepatocellular iron storage and efflux. ( info) |
10/80. Molecular characterization of a case of atransferrinemia. Hereditary atransferrinemia is a rare but instructive disorder that has previously been reported in only 8 patients in 6 families. It is characterized by microcytic anemia and by iron loading, and can be treated effectively by plasma infusions. We now report the first case known in the united states. We determined the sequences flanking the exons of the human transferrin gene and sequenced all of the exons and some of the flanking regions of the patient's dna and that of her parents. The patient's dna revealed a 10-base pair (bp) deletion, followed by a 9-bp insertion of a duplicated sequence. There was also a G-->C transversion at complementary dna (cDNA) nt 1429, predicting that a proline was substituted for the alanine in amino acid position 477 (Ala 477 Pro). The latter mutation occurs at an evolutionarily highly conserved site; 704 control alleles were screened and this point mutation was not found. Each of the patient's transferrin genes contains one mutation, ie, the patient is a compound heterozygote for these mutations, because one was found in each of her parents. In addition to these mutations, which we regard to be causative in the patient's atransferrinemia, a silent polymorphism at cDNA 1572 G-->C was found in exon 13 as well as 2 previously unreported polymorphisms at IVS8 62 c-->t and IVS14-4 c-->a. The mutation in nt 1572 and that in intron 8 were common in the general population; the intron 14 mutation is rare. ( info) |