The impact of TACI mutations: from hypogammaglobulinemia in infancy to autoimmunity in adulthood.

Common variable immunodeficiency (CVID) is considered the most common symptomatic antibody deficiency and, although mainly reported in adults, it may present from childhood. Few data on the impact of TACI defects on the clinical and immunological status of children are available. We screened 42 hypogammaglobulinemic children to investigate the frequency and mutational features of TACI defects. The genetic, clinical and immunological characterization was extended to 31 relatives of 11 children with TACI mutations. Of interest, our analysis showed a considerably higher mutation frequency in hypogammaglobulinemic children (13/42; 31%) than in other cohorts of adult patients. In seven out of nine families with the C104R variant, the prevalence of autoimmunity was significantly higher in C104R heterozygous relatives (8/15; 53%) than in those with no C104R mutation (1/11; 9%). Our data suggest a different impact of TACI mutations, from hypogammaglobulinemia in children to autoimmune disease in adulthood.

Multiple oral and cerebral relapses of a Granular cell tumor (Abrikossoff Tumor) in a young girl affected by congenital dyserythropoietic anemia type II.

CASE REPORT: A 14-year-old girl presented with 1 cm large whitened lesion on the ventral surface of the tongue, appeared from 1 month. Past history showed congenital dyserythropoietic anemia type II. The lesion was excised and microscopic and immunohistochemical analyses were compatible with benign Abrikossoff tumor. Total body MRI was negative. After six months the patient presented a second tongue lesion and four months later another large painful lesion in the soft palate, with the same istological diagnosis. In addition, she had other multiple lesions: two apperead at pharyngeal level (not biopsied) that remain stable over time, and one at the pituitary gland. CONCLUSION: Granular cell tumors, with or without multiple lesions, are rare in children. About 50% of cases involve the head and neck region, with the tongue being the most affected site. Therapy is based on the surgical excision of the lesions; however some tumor forms, although their histological aspect of benignity, often have an important infiltrative power, making the therapeutic approach difficult, as in our case.

The longitudinal biomonitoring of residents living near the waste incinerator of Turin: Polycyclic Aromatic Hydrocarbon metabolites after three years from the plant start-up.

The waste-to-energy (WTE) incinerator plant located in the Turin area (Italy) started to recover energy from the combustion of municipal solid waste in 2013. A health surveillance program was implemented to evaluate the potential health effects on the population living near the plant. This program included a longitudinal biomonitoring to evaluate temporal changes of some environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), in residents living in areas near the Turin incinerator (exposed group, E) compared to those observed in subjects living far from the plant (not exposed group, NE). Ten monohydroxy-PAHs (OH-PAHs), consisting in the principal metabolites of naphthalene, fluorine, phenanthrene, and pyrene, were analyzed in urines collected from the E and NE subjects after one (T1) and three years (T2) of plant activity and compared with those determined in the same cohort established before the plant start-up (T0). Spearman correlation analysis was undertaken to explore possible associations between OH-PAHs and personal characteristics, lifestyle variables, and dietary habits. A linear mixed model (LMM) approach was applied to determine temporal trends of OH-PAHs observed in the E and NE subjects and to evaluate possible differences in trend between the two groups. Temporal trends of OH-PAHs determined by LMM analysis demonstrated that, at all times, the E group had concentrations lower than those assessed in the NE group, all other conditions being equal. Moreover, no increase in OH-PAH concentrations was observed at T1 and T2 either in E or in NE group. Significant positive correlations were found between all OH-PAHs and smoking habits. Regarding variables associated to outdoor PAH exposure, residence near high traffic roads and daily time in traffic road was positively correlated with 1-hydroxynaphthalene and 1-hydroxypyrene, respectively. In conclusion, no impact of the WTE plant on exposure to PAHs was observed on the population living near the plant.

Extramedullary hematopoiesis in the facial sinus in a patient homozygous for Hemoglobin Lepore: the first case in literature.

Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside the bone marrow. The most affected areas are paravertebral ones. We report the case of a patient with homozygous Hb Lepore, not regularly transfused since the age of four years until the age of 29 years, when paravertebral heterotopic masses were first observed. After about 10 years she started reporting clinical signs suggestive of sinusitis. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) showed heterotopic masses in the ethmoid and in the frontal sinuses. Involvement of the sinuses of the large facial area represents a rare localization of EMH. Various cases have been reported in patients with thalassemia intermedia, but no case has been reported with HbLepore. The diagnostic gold standard is MRI, which provides highly accurate and clear images. The treatment is based on hydroxyurea and/or an intensive transfusional regime and sometimes on surgery.

Biomonitoring of the adult population living near the waste incinerator of Turin: Serum concentrations of PCDDs, PCDFs, and PCBs after three years from the plant start-up.

In September 2013 a waste-to-energy (WTE) incinerator located in the Turin area (Piedmont, Northern Italy) started to produce energy by the incineration of municipal solid wastes. The plant, one of the largest WTE incinerator in Europe, burns up to 490,000 tons of waste per year. A health surveillance program was implemented in order to evaluate the potential health effects on the population living near the plant. This program included a biomonitoring study aimed at assessing levels of several environmental contaminants including, among others, PCDDs, PCDFs, and PCBs. Before the WTE incinerator start-up (T0), a group of 85 subjects (41 "exposed" and 44 "not exposed" subjects) was randomly selected for enrollment by the local health units among individuals aged 36-50 years who had been living in the same area for at least five years prior to the study. Subjects were balanced by exposure area, sex and five-year age classes. As from the study design, the same cohort was re-evaluated after three years of incinerator activity (T2). A parallel study was conducted on a group of 12 farmers living and/or working in farms located in an area in the range of 5 km around the incinerator. Results of this study did not evidence any impact of the WTE plant on human exposure to PCDDs, PCDFs, and PCBs. In fact, no significant differences were found in the concentrations of PCDDs + PCDFs, DL-PCBs, and NDL-PCBs measured in the population group residing near the plant after three years of activity (T2) with respect to the control group. A significant decrease of serum concentrations of all the analytes was observed at T2 in both groups compared to T0. Serum concentrations of PCDDs, PCDFs, and PCBs in the group of farmers were higher than those observed in the adult population under study.

Retinal vein occlusion in child with rare mutations in genes for thrombophilia.

INTRODUCTION: Retinal vein occlusions (RVOs) are rare in the younger population. Hematological pro-thrombotic factors are thought to be important in a minority, amplifying an atherosclerotic anatomical predisposition. CASE REPORT: Anotherwise healthy 13-year-old girl presented two episodes of sudden decreased vision in few months.Ophthalmological exams pointed out post-thrombotic intra-retinal hemorrhage. All investigations were normal, thrombophilia screen showed factor XII deficiency and genetic mutations of methylenetetrahydrofolate reductase (MTHFR), angiotesin convertin enzyme (ACE) and angiotensinogen (AGT). Two intravitreal injection of bevacizumab was administered with improving visual acuity; subsequently the patient did not report further episodes. DISCUSSION: In addition to traditional factors with procoagulant activity, factor XII deficiency plays an important role in thrombosis's mechanism. Its deficiency causes a marked prolongation of the activated partial thromboplastin time in the laboratory examination. Moreover also MTHFR, ACE and AGT could have been involved in this case, so it is important to evaluate these parameters in the differential diagnosis of RVOs.

Different stages of B cell differentiation in non-T acute lymphoblastic leukemia.

Immunoglobulin heavy chain gene rearrangement was evaluated in 19 cases of acute lymphoblastic leukemia (ALL) and correlated with the immunological phenotypic expression on primary or phorbol diester (12-O-tetradecanoylphorbol-13-acetate [TPA])-induced cells. One case of common ALL (cALL), one case of T-ALL, and one undifferentiated acute leukemia that responded to anti-myeloid drugs after unsuccessful anti-lymphoid induction therapy, had germ line heavy chain genes. Rearranged immunoglobulin genes were instead found in 15 of the 16 cALL cases studied and in a case of non-T, non-B, non-common ("null") ALL, which suggested the B cell origin of the neoplastic cells. All cases bearing a heavy chain gene rearrangement were HLA-DR positive. However, the unique cALL case with a germ line configuration was also HLA-DR positive, which confirmed that both the cALL antigen and HLA-DR antigen were not per se expression of B cell commitment. On the other hand, a complete search for B cell-related markers (BA-1 and B1 monoclonal antibodies, as well as cytoplasmic immunoglobulins [CyIg]) in the cALL cases showed that at least one B cell marker could be detected either on primary or on TPA-induced cells in all cases in which a gene rearrangement had occurred. Incubation with TPA allowed the detection of one B cell marker in a case in which the primary cells were negative, and increased the expression of B cell markers in all but one of the cALLs tested. The only cALL case that was not rearranged expressed no B cell markers either on primary or on TPA-induced cells. The non-T, non-B, non-common ("null") case that was rearranged also showed no phenotypic evidence of B cell markers on primary and induced cells. These findings indicate that: (a) practically all cases of cALL appear to be of B cell origin as shown by gene rearrangement analysis; (b) DNA studies are relevant for a more precise characterization of individual cases of undifferentiated acute leukemia; (c) a complete survey for B cell markers may establish the B cell origin of the cALL blasts, as long as the analysis on primary cells is complemented by differentiation induction assessment; and (d) most cases of non-T ALL appear to be characterized by the expansion of neoplastic cells "frozen" at different levels along the B cell differentiation pathway, the first detectable marker being heavy chain gene rearrangement, followed by BA-1, B1, and CyIg expression.

Occupational exposure to PCDDs, PCDFs, and DL-PCBs in metallurgical plants of the Brescia (Lombardy Region, northern Italy) area.

The concentration values of polychlorodibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and dioxin-like polychlorobiphenyls (DL-PCBs) in blood serum samples (pools) of metallurgical workers in the area of the city of Brescia (northern Italy) were statistically processed. As to workers' exposure characteristics, pools were divided into 34 professionally exposed (PE) and 11 non-professionally exposed (NPE). A further subdivision of PE pools was according to workplaces in which ferrous (N = 24) and non-ferrous (N = 10) materials were handled. To evaluate the aforesaid differences we applied the age-adjusted Generalized Linear Models. We identified significant (P ≤ 0.05) exposure models of the classification groups. The first subdivision was confirmed by the concentrations of 1,2,3,4,6,7,8-H7CDF, DL-PCB 105, and DL-PCB 189; the second was confirmed by the concentrations of PCDF TEQ97, PCDD + PCDF + DL-PCB (TEQTOT) TEQ97, 2,3,4,7,8-P5CDF, 1,2,3,6,7,8-H6CDD, 1,2,3,4,6,7,8-H7CDD, and PCB 189. Based on the literature, all mentioned congeners have been found in stack gas and fly ash samples of metallurgical plants: therefore, these indicators indicate the exposure to such work environments. Specifically, the concentrations measured in the workers' blood serum appear to depend on the type of material processed during work.

Expression of transduced carcinoembryonic antigen gene in human rhabdomyosarcoma inhibits metastasis.

Carcinoembryonic antigen (CEA) is a highly glycosylated cell surface glycoprotein belonging to the immunoglobulin superfamily. CEA has been involved in vitro in adhesion mechanisms, but little is known about the function of this glycoprotein in vivo in normal tissue differentiation and malignancy. With regard to the relationship between CEA expression and tissue differentiation, it has been reported that transfection of the CEA gene in rat L6 myoblasts results in a complete block of myogenic differentiation. To extend investigations to the transformed myogenic counterpart and examine CEA effects on differentiation and malignancy outside the colon system, we have transfected the human CEA gene in human rhabdomyosarcoma cells. Human rhabdomyosarcoma cells transfected with the CEA gene correctly expressed membrane CEA anchored via glycosylphosphatidylinositol and secreted CEA in the medium. CEA gene transfer in human rhabdomyosarcoma cells, which display a limited differentiation ability, does not further inhibit myogenic differentiation or alter in vitro proliferation or natural killer sensitivity. CEA transfection does not affect s.c. growth in nude mice, but the ectopic expression of CEA in human rhabdomyosarcoma cells can strongly inhibit their metastatic ability to lungs and adrenals after i.v. injection. The impairment of metastatic potential correlates with a reduction in the homotypic adhesion properties of the cells. These data suggest that CEA, in some systems, can interfere with intercellular adhesion and, at least for cells not metastatic to the liver, can act as an anti-metastatic molecule.

Potential impact on food safety and food security from persistent organic pollutants in top soil improvers on Mediterranean pasture.

The organic carbon of biosolids from civil wastewater treatment plants binds persistent organic pollutants (POPs), such as polychlorodibenzo -dioxins and -furans (PCDD/Fs), dioxin and non-dioxin -like polychlorobiphenyls (DL and NDL-PCBs), polybrominated diphenyl ethers (PBDEs), and perfluorooctane sulfonic acid (PFOS). The use of such biosolids, derived digestates and composts as top soil improvers (TSIs) may transfer POPs into the food chain. We evaluated the potential carry-over of main bioavailable congeners from amended soil-to-milk of extensive farmed sheep. Such estimates were compared with regulatory limits (food security) and human intakes (food safety). The prediction model was based on farming practices, flocks soil intake, POPs toxicokinetics, and dairy products intake in children, of the Mediterranean area. TSI contamination ranged between 0.20-113 ng WHO-TEQ/kg dry matter for PCDD/Fs and DL-PCBs (N = 56), 3.40-616 µg/kg for ∑6 NDL-PCBs (N = 38), 0.06-17.2 and 0.12-22.3 µg/kg for BDE no. 47 and no. 99, 0.872-89.50 µg/kg for PFOS (N = 27). For a 360 g/head/day soil intake of a sheep with an average milk yield of 2.0 kg at 6.5% of fat percentage, estimated soil quality standards supporting milk safety and security were 0.75 and 4.0 ng WHO-TEQ/kg for PCDD/Fs and DL-PCBs, and 3.75 and 29.2 µg/kg for ∑6 NDL-PCBs, respectively. The possibility to use low-contaminated TSIs to maximize agriculture benefits and if the case, to progressively mitigate highly contaminated soils is discussed.

Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

PURPOSE: To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS: Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS: Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION: Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.

PURPOSE: To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS: All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS: In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION: Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.

Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia.

Forty-seven patients with primary refractory, relapsed, and previously untreated, poor risk AML were entered into a phase II study of intermediate dose ARA-C (IDAC) (1 g/m2 i.v. over 6 hr, daily for 6 days) with sequential mitoxantrone (MITOX) (6 mg/m2 i.v. bolus 3 hr after the end of each ARA-C infusion). Overall, complete remission was induced in 31 patients (66%), and 1 additional patient entered a partial remission. Seven patients (15%) died of infection during marrow hypoplasia. Response to IDAC + MITOX was influenced by sensitivity to previous therapy: patients with primary refractory and early relapse AML responded less well to the regimen (CR rate 28% and 33%, respectively), as compared to those with previously untreated (CR rate 64%) or late relapse disease (CR rate 85%). Sixteen patients continue in CR at 1-12+ months. Except for the expected severe myelosuppression, the regimen was well tolerated with minimal extramedullary toxicity. The data indicate that the sequential combination of IDAC and MITOX is an effective and tolerable regimen for AML. Consideration should be given to applying this program at earlier stages of AML therapy.

Second allogeneic bone marrow transplantation in acute leukemia: a multicenter study from the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO).

Thirty-eight second allogeneic bone marrow transplants (BMT) for acute leukemia relapsed after first BMT were performed in 13 Italian centers between 1987 and 1994. Twenty-one patients had acute myelogenous leukemia (AML), 17 acute lymphoblastic leukemia (ALL); at second BMT 24 patients were in complete remission (CR) and 14 in relapse. The median time to relapse after first BMT was 10 months (range 1-70). Grade II or greater acute graft-versus-host disease (GVHD) after second transplant occurred in 34.2% of patients and a chronic GVHD in 31.5% of patients. Twenty-four patients died: seven from early transplant-related mortality (TRM), 13 from relapse and four from late toxicity. As of 31 July 1996, at a median follow-up of 47 months (range 22-85), there are 14 survivors. The three-year probability of TRM, relapse and event-free survival (EFS) is 28%, 40% and 42% respectively. In 20 of 27 evaluable patients, remission duration after second BMT was longer than after the first BMT. A diagnosis of AML was correlated with a better outcome. These data support the usefulness of second allograft in selected patients with AML relapsing after a first BMT.

Genotypic characterization of common acute lymphoblastic leukemia may improve the phenotypic classification.

The reactivity of five anti-B monoclonal antibodies (McAb)-OKB2 (CD24), B4 (CD19), Leu12 (CD19), BA1 (CD24), B1 (CD20)--as well as the presence of cytoplasmic immunoglobulins (CyIg) were assessed in 100 cases of common acute lymphoblastic leukemia (cALL) at presentation (TdT+, J5 [CD10]+, HLA-Dr+). All cases studied revealed one or more B-cell related markers and a hierarchy in their expression was documented: OKB2 was positive in all cases tested (100%), B4 was expressed in 96.4% of cases, Leu12 in 95.8%, BA1 in 94.9%, B1 in 18.3%, and CyIg in 23%. Further evidence of the B-cell origin of cALL was obtained by molecular analyses at the DNA level which demonstrated the presence of an Ig heavy chain gene rearrangement in all 37 cases assessed, while 37.8% showed a light chain gene reorganization. A genomic subclassification of cALL demonstrated that the majority of cases showed an immature molecular configuration with one (8.1%) or both (54.1%) Ig heavy chain alleles rearranged and a germ-line configuration of the light chain genes; 27% revealed a heavy chain gene involvement and one k allele rearranged. Only four cases (10.8%) showed a more mature configuration with both k alleles rearranged or a gamma chain gene involvement. This study confirms that cALL is characterized by the proliferation of immature B-lineage-committed elements and indicates that the leukemic cells are blocked at different levels of B-differentiation which may be recognized with the use of multiple phenotypic or genotypic B-cell-related markers.

Analysis of immune reconstitution in children undergoing cord blood transplantation.

OBJECTIVE: The aim of this study was to investigate and compare immune reconstitution in allogeneic cord blood transplantation (CBT) and bone marrow transplantation (BMT) recipients. MATERIALS AND METHODS: Twenty-three children underwent CBT from either human leukocyte antigen-identical siblings (11 cases) or unrelated donors (12 cases) were enrolled in the study, together with 23 matched children receiving BMT. Patients were analyzed 2-3 and 12-15 months after transplant. Recovery of T-, B-, and NK-lymphocyte subsets, proliferative in vitro response to mitogens, as well as cytotoxic activities, were investigated. RESULTS: CBT recipients showed a marked increase in the number of B lymphocytes as compared with patients who underwent BMT (p < 0.001). The absolute number of CD3(+) and CD8(+) T cells, as well as the proliferative response to T-cell mitogens, recovered with time after transplantation, irrespective of the source of stem cells used. Recipients of unrelated CBT had a better recovery of CD4(+) T lymphocytes (p < 0.01). Among patients experiencing acute graft-versus-host disease (GVHD), children given CBT had a much greater production of CD4(+) CD45RA(+) T cells than BMT recipients (p < 0.005). Recovery of NK cell number and innate cytotoxic activities was fast, irrespective of the source of stem cells used. CONCLUSIONS: Despite the much lower number of lymphocytes transferred with the graft, recovery of lymphocyte number and function toward normal in CBT recipients was rapid and comparable to that observed after transplantation of bone marrow progenitors. This prompt immune recovery possibly was favored by the reduced incidence and severity of GVHD observed in children who underwent CBT.

Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P < 0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.

BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. METHODS: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. RESULTS: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019). CONCLUSION: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

Rebound thymic hyperplasia following high dose chemotherapy and allogeneic BMT.

We describe a child with acute lymphoblastic leukemia who showed mediastinal widening 8 months after allogeneic BMT. Total thymectomy was carried out by the transcervical approach. Histologic examination showed only thymic hyperplasia. The immunohistologic investigation revealed a normal distribution of thymic cell elements, without evidence of clonal proliferation of lymphocytic subpopulations. This case supports the hypothesis that thymic hyperplasia following chemotherapy may be merely a rebound phenomenon. The patient had an uneventful postoperative recovery and remains in remission more than 1 year after BMT.

Autologous bone marrow transplantation in children with acute myeloblastic leukemia: report from the Italian National Pediatric Registry (AIEOP-BMT).

This report summarizes indications and results of autologous bone marrow transplantation (ABMT) performed in childhood acute myeloid leukemia (AML) in Italy since 1984. A total of 158 patients have been reported from 12 teams to the AIEOP-BMT Registry: 110 have been autografted in first complete remission (CR) and 48 in second remission. Several conditioning regimens have been utilized, mainly consisting of BAVC (an original polichemotherapy schedule, BCNU, mAMSA, VP-16 and Ara-C) (63 cases) and of total body irradiation (TBI) plus Melphalan (33 cases): other 28 patients received different TBI-including regimens, and 34 received various chemotherapy regimens (Busulfan plus cyclophosphamide +/- VP-16, Busulfan plus Melphalan, Melphalan alone). Projected event-free survival (EFS) for patients autografted in first CR is 41.4% (S.E. 5.5%) at 7 years, with a total of 53 patients in continuous CR. EFS is better in patients receiving a TBI-including regimen: 78.8% versus 27.2% (p = 0.0001). In particular, results obtained in a subgroup of 21 cases receiving TBI + melphalan and purged marrow are particularly encouraging, with a EFS > 85% projected a 7 years. The overall EFS in second CR is 41.5% at 7 years, and no difference have been observed after a TBI-including regimen or after a chemotherapy regimen, being EFS 43.1% and 39.3% for these 2 groups respectively. A total of 11 transplant-related deaths occurred, with 5 patients (4.5%) dead in first CR and 6 (12%) dead in second CR within 100 days from transplant. From these data, ABMT is confirmed to represent an effective treatment for AML after first relapse, while the encouraging results obtained in first CR with TBI-including regimens should be confirmed with a longer follow up and a larger number of patients.