A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune ...thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.
Centro Trapianti di Midollo, Ospedale Maggiore di Milano, I.R.C.C.S., Universita degli Studi di Milano, Italy.
BACKGROUND. Fungal infections still represent a major clinical problem in neutropenic ...patients; the recent availability of active imidazole derivatives, particularly fluconazole and itraconazole, has increased interest in prophylaxis. MATERIALS AND METHODS. Fifty-nine consecutive bone marrow transplant (BMT) recipients were randomized to receive either itraconazole 400 mg/day or fluconazole 300 mg/day as oral antimycotic prophylaxis during the pancytopenic phase; they were retrospectively compared with a historical control group of 30 patients who had received fluconazole 50 mg/day. Every febrile episode was treated with the same empirical antibiotic combination; amphotericin-B was added after 4-5 days in the case of persistent fever. Proven or suspected mycotic infections and the empirical use of amphotericin-B were considered as failures of prophylaxis. RESULTS. There were no differences in the number of febrile episodes in the three groups. Five patient died of bacterial sepsis: two in the fluconazole 300, two in the itraconazole and one in the fluconazole 50 group. The addition of amphotericin-B was required in 12, 16 and 11 cases, respectively, in the three groups. There were four documented fungal infections in the intraconazole and one in both fluconazole groups; three suspected fungal infections were observed in the fluconazole 300 group and two in both the itraconazole and the fluconazole 50 group. None of the differences were statistically significant. CONCLUSIONS. The present results indicate that high-dose fluconazole and itraconazole are equivalent; neither of them was superior to low-dose fluconazole, which is regarded as being devoid of prophylactic activity against systemic mycoses.
A discrepancy exists worldwide between the number of suitable liver donors and the increasing demand for transplantation. Thus many centers have considered widening their liver donor acceptance ...criteria and this may increase the incidence of primary dysfunction (PD) with negative effect on the results of transplantation. In order to reduce the incidence of PD and improve patient and graft survival it becomes important to identify those risk factors associated with its occurrence. In a retrospective univariate and multivariate analysis we evaluated several donor, preservation and recipient parameters and their correlation with PD. In our Department 282 orthotopic liver transplantations (OLT) were performed on 256 adult patients over a 10-year period. Excluded were 15 cases with early vascular problems and 4 intraoperative deaths. A complete series of donor, recipient and procedure-related data were analyzed. About 30% of donors showed abnormal values. In 70 cases of PD (26%) there was a 61.4% graft failure rate compared with 15% in the group with immediate function (P < 0.05). Univariate analysis showed donor age, steatosis, ischemia time, amines, oliguria, hypotension and ICU stay to be significantly associated with PD. Multivariate analysis showed steatosis, ischemia time and amine dosage to be independent risk factors for the development of primary non function. In conclusion, the acceptance of marginal donors worsened the results of transplantation, but the rejection of these donors would reduce by about 30% our transplant activity resulting in increased mortality in the waiting list. Combinations of risk factors when possible should be avoided, and ischemia time, as the only variable that can be controlled, should be kept as short as possible.
Haematopoietic reconstitution after autologous stem cell transplantation (ASCT) was evaluated at different times in 26 lymphoma patients. All of the patients showed a significant decrease in the ...number of both committed (CFU-C) and more primitive progenitor cells (LTC-IC). The expansion of bone marrow progenitor cells in a 'stroma-free' long-term liquid culture system supplemented with SCF, IL-3, IL-6 and GM-CSF from 19 transplanted patients was significantly reduced compared to normal controls. The stromal cell compartment, evaluated by means of a CFU-F assay, was also greatly reduced. The number of haematopoietic and stromal cell progenitors was, nevertheless, very similar to their pre-transplant values. Bone marrow histology, which was evaluated at different times after transplant, showed an increase in reticulin fibres, the dilatation of parenchymal sinusoids and some morphological evidence of trilineage dysplasia in 11 patients; however, the same abnormalities were seen in the majority of pre-transplant samples. No cytogenetic abnormalities were observed in 15 patients before transplant, but four subsequently developed persistent clonal karyotypic alterations and five showed non-clonal abnormalities that generally disappeared over time. Our data suggest that both the stromal and the haematopoietic compartments are somehow damaged after ASCT for lymphoma; however, these defects generally pre-exist the transplant conditioning regimen and seem to become less pronounced over time.
The aim of this study was to demonstrate the efficacy and safety of the sublingual-swallow allergen-specific immunotherapy (SLIT) in a paediatric population suffering from allergic rhinitis and ...related pathologies. From March 1994 through March 2000, at our ENT Department 4000 children (1800 males and 2200 females), aged 3 to14 years, were examined for recurrent nasal obstruction and nasal polyps. 2400 (60%) of them were allergic and underwent the following investigations: Impedance test, Pure tone audiometry, rhinomanometry, Prick test, RAST, nasal provocation test and paranasal sinus TC without contrast media. Of the allergic group we admitted 288 patients(12%) to a 3 yr SLIT, meeting the following criteria: children aged 5 years or more, mono-sensitised to one allergen and with family cooperation support. After three years of SLIT, we observed complete symptom remission and a marked improvement in instrumental examinations in 80% of these children. The improvement was poor in 8% of patients, while in 12% of the subjects no changes in symptoms and instrumental results were detected. These results are in agreement with previously published studies and confirm that SLIT can be a valid tool for treating allergic upper respiratory tract diseases in children.
We evaluated the in vitro effect on clonogenic potential (CFU-GM) and apoptosis in myelodysplastic syndromes (MDS) progenitors of an anti-oxidant (
N-acetylcysteine, NAC) and/or a differentiating ...(all-
trans retinoic acid, ATRA) agent. NAC significantly reduced apoptosis, both NAC and ATRA induced an increase in CFU-GM, but NAC seemed to be particularly effective in the high risk (HR) MDS. NAC+ATRA conferred a significant advantage in terms of CFU-GM with respect to NAC and ATRA alone. Tumor Necrosis Factor-α (TNF-α) levels decreased after incubation with NAC in the MDS samples. This study shows that ineffective hemopoiesis in MDS could benefit from both NAC and ATRA, suggesting that anti-oxidant treatment may play a role in guaranteeing MDS cell survival, predisposing them towards differentiation.
We have recently observed 29 cases of metabolic syndrome (MS) in 85 adult long-term hematopoietic stem cell transplantation (HSCT) survivors, a significantly higher prevalence than that observed in ...Italian cohort studies. These subjects (15 women and 14 men; mean age 49.8 + or - 9.3 years; 17 autologous and 12 allogeneic transplant recipients) were compared with 29 patients with "classical" MS (15 women and 14 men; mean age of 52.9 + or - 8.0 years) and 39 healthy subjects (19 women and 20 men; mean age 40.1 + or - 16.9 years) in terms of height, weight, waist circumference, body mass index (BMI), blood pressure, fasting plasma glucose, and serum triglycerides, HDL cholesterol, leptin and insulin levels. Serum leptin levels were statistically significant different in the three groups (c2 test: 31.8; p<0.001) and every post-hoc test was also significant, particularly those between the subjects with "classical" or post-HSCT MS (Mann-Whitney U test: 220.0; Z -2.8; p=0.004). A general linear model consisting of serum insulin (p=0.025), BMI (p<0.001), gender (p<0.001), group (healthy, post-HSCT MS, "classical" MS; p<0.001), and the interaction between gender and group (p<0.001) explained 71% of the variability in leptin levels (adjusted R.sup.2 = 0.711). There were no significant differences in serum leptin or insulin levels between the allogeneic and autologous HSCT recipients. Serum leptin levels and BMI were linked in the patients with "classical" MS but not in those with post-HSCT MS. Hyperleptinemia is considered a marker of MS, and we observed significantly higher leptin levels in post-HSCT MS than in "classical" MS or healthy subjects. As the physiological correlation between leptin and BMI was lost, the hyperleptinemia in post-HSCT MS is not simply related to an increase in central obesity, and could be related to its role in immune response. Cytokines such as TNF-alpha, IL-1 and IL-6 regulate leptin expression, and leptin modulates T cell response by polarising T helper cells toward a Th1 phenotype. One previous study of hyperleptinemia in HSCT recipients found the highest values in those with chronic graft-versus-host disease, but we have previously found that allogeneic HSCT and GVHD are not associated with a higher risk of MS than autologous HSCT. Hyperleptinemia could represent a primary event in the pathogenetic mechanism leading to the development of post-HSCT MS as a result of interactions between leptin and immune function.
Hepatitis B (HBV) infection prevalence is frequently reported as increased among hematological patients. This enabled us to start reviewing HBV serology in our HSCT recipients. Moving back over the ...last four years we collected a series of 238 consecutive HSCT recipients (male 129, female 109, median age 50 years, range 18-70, autologous 151, allogeneic 87). The baseline diagnoses were lymphoma in 96, acute leukemia in 59, CLL and myeloproliferative disorder in six each, multiple myeloma in 47, PNH in 5 and autoimmune disease (AD) in 19 cases. Five patients were HBSAg positive, 54 had isolated anti-HBS antibodies (14 vaccinated), 38 were simultaneously anti-HBS and anti-HBC positive, and eight had anti-HBC without anti-HBS antibodies. Anti-hepatitis C (HCV) antibodies were observed in five patients. As a whole, 91/224 not vaccinated patients (40.62%) showed some kind of HBV positivity. Of 19 patients with AD, three were vaccinated, three had isolated anti-HBS and one isolated anti anti-HBC positivity. Therefore, 87/208 not vaccinated neoplastic patients (41.82%) showed some kind of anti-HBV positivity, with 46/208 having anti-HBC antibodies without HBSAg positivity (22.11%). Even dividing the series by ten-year age cohorts, the prevalence of anti-HBC positivity was higher in comparison with the reference populations in European prevalence studies, showing median values below 10% and 16-17% in the worst age cohorts; no reliable comparisons are available for isolated anti-HBS positivity. Hematologic patients have an up to 40% rate of HBV positivity, including both HBSAg and anti-HBS/anti-HBC. Nevertheless, a deeper understanding is hindered by the quality of data in the reference populations, since prevalence study either report blood donors series, a somewhat selected population, or encompass relatively small series. The imbalance between general population and hematologic patients is a persistent finding over time, despite the evolving pattern of HBV diffusion and the increasing proportion of European population accounted for by people coming from countries at high HBV endemics. The contrast is somewhat surprising between the interest in the relationships between HCV and lymphomas, and the matter of HBV infection in hematology, mainly focusing on the prevention of HBV complications. The question may be raised as to whether HBV infection should also be considered as a risk factor in the development of hematologic neoplasms.
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