Role and clinical importance of Helicobacter pylori infection in hemodialysis patients.

Dyspepsia is an extrarenal symptom frequently found in hemodialysed patients; it is due to chronic renal failure, and uremic gastritis is a specific associated condition in chronic renal failure (CRF). On the other hand, in the general population, Helicobacter pylori infection is an important dyspepsia-related risk factor; its close connections with gastro-duodenal pathology are already known, above all the peptic disease in a really exclusive way. By observation of a dyalitic group of patients, opportunely matched with a no CRF group, we evaluated CRF-associated uremia and Helicobacter pylori infection which could eventually interact causing symptoms and lesions. A statistical analysis of obtained data allowed us to conclude that, although there is not, from an epidemiological view-point, a larger diffusion of Helicobacter pylori among dyalitic patients compared to general population, moreover the infection is uremia-synergic in causing gastro-duodenal symptoms and lesions. These findings, therefore, suggest systematically investigation a possible Helicobacter pylori infection in CRF patients and its relation to gastritis grading, and searching for probable active peptic lesions.

Hepatitis C virus infection in hemodialyzed patients.

In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in noninfected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.

Treatment of childhood acute lymphoblastic leukemia. Long-term results of the AIEOP-ALL 87 study.

BACKGROUND AND OBJECTIVES: In March 1987 AIEOP started the AIEOP-ALL-87 study, based on the previous AIEOP-ALL-82. The aim of this new study was to evaluate, for all risk groups: a) the efficacy of treatment intensification achieved by adding a fourth drug (daunomycin) in the induction phase and a 3-drug reinduction phase for all risk groups; b) the impact of the addition of three doses of intrathecal methotrexate during cranial radiotherapy and extended exposure to weekly high-dose L-aspariginase during late intensification in high risk patients. We report the long-term results of the AIEOP ALL-87 study. DESIGN AND METHODS: From 1987 to 1991, a total of 632 eligible and evaluable children (age 1 to < or =16 years) with non-B-cell acute lymphoblastic leukemia (ALL), were enrolled and stratified as follows: standard risk (SR, 79 patients, 12.5%) had WBC <10,000/mm3, age > or = 3 and <7 years, and FAB L1 morphology. The high risk (HR, 175 patients, 27.7%) group included patients with WBC > or =50,000/mm3 or FAB L3 morphology or T immunophenotype or acute undifferentiated leukemia (AUL) or leukemia-lymphoma syndrome. All the remaining patients formed the intermediate risk group (IR, 378 patients, 59.8%). All patients received a 4-drug induction therapy; intermediate-dose methotrexate was given to HR patients; cranial radiotherapy was given to IR and HR patients, while SR patients received extended intrathecal methotrexate; all patients received a 3-drug reinduction phase; high dose L-asparaginase (HD-L-ASP; E.Coli, Bayer) was given to HR patients; continuation therapy with 6-mercaptopurine, i.m. methotrexate, and monthly vincristine and prednisone pulses was given to all patients. Treatment duration was 2 years. RESULTS: Six hundred and nineteen patients (97.9%) achieved complete remission. The remission rate was 98.7% in the SR group, 98.1% in the IR group, and 97.1% in the HR group. The overall 10-year survival and event-free survival (EFS) rates (SE) are 74.7% (1.8) and 62.8% (2.0) respectively; EFS rates by risk group are 67.5% (5.5) in SR, 62.8% (2.6) in IR, and 61.9% (3.8) for HR. The 10-year EFS for all eligible patients was 63.9% (1.9). INTERPRETATION AND CONCLUSIONS: When compared to the results of the AIEOP-ALL-82 study, treatment intensification in the ALL-87 study has improved long-term survival and EFS from 66.4% and 53.6% to 74.7% and 62.8%, respectively. Failures were mostly due to marrow or extramedullary relapses suggesting that further treatment intensification, as being used in current therapeutic strategies, is appropriate, although patients relapsing after less intensive treatment may have better chances of rescue. These results, although obtained in a relatively large proportion of patients, in which infants were not included, indicate that the addition of high-dose L-asparaginase to a relatively non-intensive treatment may be of major benefit for HR patients and that the addition of intrathecal methotrexate during CRT, may improve the central nervous system-disease control with a marked reduction of nervous system relapses.

Prevalence of biliary lithiasis in a Sicilian population of hemodialysis patients.

Studies performed to date on the prevalence of biliary lithiasis (BL) in chronic renal failure patients on hemodialysis (HD) have given contradictory results. The aims of the present study were to evaluate the prevalence of BL and its main associated risk factors in a population of hemodialysis patients, and to compare the results with those we had obtained previously in an overt population of the same zone. The study included 171 patients (83 M, 88 F), mean age 62.5 years and mean duration of dialysis 66.7 months. The screening protocol also included body mass index (BMI), a number of biochemical parameters and an ultrasound scan of the gallbladder and biliary tract. The general prevalence of BL was 33.3% (30.1% in men and 36.4% in women), and this figure was significantly higher than that found in our previous study. Prevalence increased with age in both sexes (Mantel-Haenszel Chi-squared = 5.4, p < 0.03), but not with duration of dialysis. The main risk factors, evaluated with multiple logisstic regression, were the presence of diabetes mellitus and high serum phosphorus levels. Specific symptoms were also significantly associated in BL patients. No association was found with parity, BMI or serum lipid alterations. In conclusion, the prevalence of BL in a Sicilian population of HD patients was higher than that found in an overt population of the same area and the associated main risk factors were not coincident. Further studies are needed to establish the role played by the phase of end-stage renal disease before HD and to correct the metabolic disturbances to limit a high percentage of morbidity in a disease already in itself sufficiently disabling.

Risk-directed therapy for childhood acute lymphoblastic leukemia. Results of the Associazione Italiana Ematologia Oncologia Pediatrica '82 studies.

BACKGROUND: In 1982, the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) started its third-generation study, aiming to improve previous results obtained by AIEOP '79 study and to deliver a standardized treatment to most Italian children with acute lymphoblastic leukemia (ALL). METHODS: We treated 902 children (older than 1 year and younger than 15 years of age) with newly diagnosed ALL in multicenter studies of risk-directed therapy (111 low risk [LR] from Study 8201; 570 average risk [AR] from Study 8202; and 117 and 104 high risk [HR] from Studies 8303 and 8503, respectively). Induction therapy was composed of vincristine, prednisone, and asparaginase for LR or AR patients and these agents plus daunorubicin, (Study 8503) or vincristine, prednisone, cytarabine, and intermediate-dose methotrexate (Study 8303) for HR patients. Central nervous system (CNS) preventive therapy consisted of intrathecal methotrexate only (LR), intrathecal methotrexate plus 18 Gy cranial irradiation (AR and HR Study 8503), or high-dose (HD) cytarabine (HR Study 8303). Reinduction therapy was vincristine/prednisone/daunorubicin for AR patients with cyclophosphamide added for HR patients in Study 8303 and HD asparaginase in Study 8503. LR patients did not receive intensification therapy. Continuation therapy comprised 6-mercaptopurine plus methotrexate and monthly pulses with vincristine plus prednisone for all patients, except for HR patients in Study 8303 who also received teniposide plus cytarabine. Weekly HD asparaginase was also given in Study 8503. Duration of treatment was 24 months for Studies 8201 and 8202, 15 months for Study 8303, and 22 months for Study 8503. The overall complete remission (CR) rate was 94.7% (97.3% for LR, 94.9% for AR, and 93.2% for HR). RESULTS: Overall 7-year event-free survival (EFS) was 53.6% (standard error [SE], 1.8). EFS was 60.8% in LR (SE, 4.7), 60.6% in AR at 7 years (SE, 4.7), and 18.5% in Study 8303 (HR) at 5 years (SE, 3.8). Because of the poor result in HR patients, a successor study (8503) was developed that yielded a 5-year EFS of 46.1% (SE, 5.1). Site-specific relapse rates were 18.5% (LR), 13.4% (AR), 35.1% (HR on 8303), and 18.3% (HR in Study 8503) for bone marrow and 9.2%, 7.9%, 17.5%, and 19.3%, respectively, for the CNS (isolated). Isolated testicular relapse was observed in 3.9% of male patients. CONCLUSIONS: This risk-directed therapy cured at least 50% of patients with ALL with relatively nonintensive therapy. The 80% overall survival rate for LR and AR patients at 7 years suggested that the total cure rate may be higher than 50% because of the significant salvage rate for patients who received antimetabolite-based therapy initially.

Treatment of pediatric Hodgkin disease tailored to stage, mediastinal mass, and age. An Italian (AIEOP) multicenter study on 215 patients.

BACKGROUND: Attempting to optimize treatment results in pediatric Hodgkin disease while minimizing major side effects, at least in early-stage patients, in 1983 the Italian Association of Pediatric Hematology and Oncology (AIEOP) conceived a multicenter study tailored according to stage, bulky mediastinal mass, and age. METHODS: Between December, 1983 and January, 1989, 215 evaluable patients (median age, 9.9 years, range, 1-15 years) received the AIEOP-MH 1983 Hodgkin disease protocol of low-dose radiation therapy (20-25 Gy), with three cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) for children with early-stage and favorable disease, and with alternating cycles of an eight non-cross-resistant drug combination regimen (nitrogen mustard, vincristine, procarbazine, and prednisone [MOPP]/ABVD) for 6 months for those with bulky and unfavorable disease. Patients in advanced stages received four additional courses of MOPP/ABVD as maintenance therapy. RESULTS: The overall survival and freedom from progression (FFP) probabilities at 7 years are 85.7% and 81.5% respectively. FFP probabilities at 7 years in Groups 1 (58 patients in Stages I and IIA with mass/thorax [M/T] < 0.33), 2 (56 patients in Stages IEA, IB, IIA with M/T > 0.33, IIB, and IIIA), and 3 (38 patients in Stages IIIB and IVA and B) were 94.8%, 81.4%, and 60.3%, respectively. Multivariate analysis showed B symptoms, M/T > 0.33, and stage to be significant, independent prognostic factors affecting survival and FFP curves. CONCLUSIONS: The encouraging results in early-stage disease indicate the validity of using less toxic treatment in this subgroup to maximize quality of life. Patients with bulky mediastinal disease tended to fare worse than those with M/T < 0.33 or without mediastinal involvement (FFP at 7 years: 69.4% versus 93.3%) and showed early local recurrence. In advanced stages, the eight-drug combination regimen (MOPP/ABVD) plus low-dose radiation therapy provided no major improvement in outcome; here, alternative chemotherapeutic regimens should be tested in a large, randomized, clinical trial to evaluate their efficacy and determine the frequency of delayed toxicity.

Anaplastic large cell lymphoma (Ki-1+/CD30+) in childhood.

In 1985, Stein et al. (Blood 66:848-858) described a large cell lymphoma consisting of activated lymphoid elements, expressing the Reed-Sternberg cell-associated antigen Ki-1 (CD30); this tumor has recently been included in the updated Kiel classification and has been termed anaplastic large cell lymphoma (ALCL). This report concerns 13 patients with previously untreated ALCL who were admitted to the Pediatric Hematology and Oncology Department of Bologna University between January 1983 and December 1989. Ten cases were diagnosed as common type ALCL, 1 as Hodgkin's-related ALCL and the remaining 2 as histiocyte-rich ALCL/lymphohistiocytic T-cell lymphoma. T-cell markers were present in 85% of the cases, and B phenotype in the remaining 15%. About one-half of the patients presented systemic symptoms; all but one showed more than one involved site, mostly an association of nodal and extranodal sites. All patients (1 in stage I, 7 in stage II, and 5 in stage III) were treated with a modified version of the LSA2-L2 protocol. Survival and event-free survival at 4 years were 100% and 62.9%, respectively. Two out of 3 relapsed patients presented a recurrence of disease when they were off-therapy 24 and 36 months after first complete remission. Good response to salvage chemotherapy of all the relapsed patients and the long duration of the second complete remission were a distinctive characteristic of this neoplasm when compared to other histological subtypes. The clinical presentation, the tendency to develop late relapses and to achieve and maintain second remission easily suggest that ALCL is a high grade non-Hodgkin's lymphoma, from the histological point of view, but is similar to Hodgkin's disease from the clinical point of view. This would confirm the hypothesis that Hodgkin's disease and ALCL represent a continuous spectrum of the same disease.

Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion.

OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary.

Wilms' tumor with transient dermolysis of the newborn: recurrence of skin lesions during chemotherapy.

Transient bullous dermolysis of the newborn consists of congenital skin defects and a tendency for blistering of the skin and mucous membranes during the neonatal period. A case of transient bullous dermolysis of the newborn associated with Wilms' tumor is reported. Transient bullous dermolysis of the newborn does not represent an obstacle to administering appropriate chemotherapy when simple precautions are taken.

In vitro growth and regulation of bone marrow enriched CD34+ hematopoietic progenitors in Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital red blood cell aplasia. No clear explanation has been given of its defective erythropoiesis, although different humoral or cellular inhibitory factors have been proposed. To clarify the nature of this defect we studied the effect of several human recombinant growth factors on an enriched CD34+ population obtained from the bone marrow of 10 DBA patients. We observed a defect underlying the early erythroid progenitors, which were unresponsive to several growth factors (erythropoietin, interleukin-3 [IL-3], IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], erythroid potentiating activity), either alone or in association. The production of cytokines was not impaired, and high levels of IL-3 and GM-CSF were found in phytohemagglutinin-leukocyte-conditioned medium (PHA-LCM) when tested with a sensitive biologic assay on the M-07E cell line. Hematopoietic stem cells in DBA patients may be induced to differentiate to the granulocyte megakaryocyte, but not the erythroid compartment, as shown after CD34+ cell preincubation with IL-3. Addition of the stem cell factor to IL-3 and erythropoietin induces a dramatic in vitro increase in both the number and the size of BFU-E, which also display a normal morphologic terminal differentiation.

Treating childhood acute lymphoblastic leukaemia (ALL): summary of ten years' experience in Italy. ALL Steering Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

Between 1976 and 1986, 2,093 children with ALL were enrolled in three consecutive generations of trials conducted by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). A 50% event-free survival at 5 years was achieved overall in this population, approximately accounting for more than 50% of the entire childhood ALL population in Italy. Participation in the group protocols increased from the original seven founding centers to the current 37 institutions. Results in the standard population (non-T immunophenotype, non-FAB L3, and less than 50,000 white blood cells (WBC/ml) were considerably better with more recent, more aggressive protocols. The two major results in this population (N = 540) were a relatively low incidence (8% at 5 years) of central nervous system (CNS) relapse in the "good"-risk population (less than 10,000 WBC, ages 3-6 years, and FAB L1), without the use of cranial irradiation, and a projected 4-year disease-free interval for bone-marrow relapse of 80% in the "average"-risk group, where a three-drug reinduction program was adopted after consolidation. Overall, the event-free survival of the most recent generation (protocol 82, median follow-up time of 38 months) is 66% at 4 years (95% confidence limits [CL] 61-71). Based on these 10 years of experience, the general strategy of the group for the 90s is outlined and discussed.