Community control of thalassemia as a model of genetic disease: experience in the Lombardy region of Italy.
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Community Health Services↗
Biomedical subjects
G Masera
Publications and source records attributed to G Masera.
Late deaths and second primary malignancies among long-term survivors of childhood cancer: an Italian multicentre study.
A multicentre registry of children who had been successfully removed from therapy for some common childhood cancers (Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, nephroblastoma, acute lymphatic leukaemia and other leukaemias) was established in Italy in 1981. The present study describes mortality and occurrence of second primary malignancies (SPMs) among 1467 children who were alive when the registry was established. Follow-up ended on December 31, 1983 for mortality and 1 year later for the occurrence of SPMs. Sixty-seven deaths were recorded, 11 of which were due to causes other than progression of the original disease. Eleven incident SPMs were identified (i.e. 3 acute myeloid leukaemias, 3 thyroid carcinomas, 1 bilateral breast carcinoma, 1 liver malignant mesenchymoma, 1 astrocytoma, 1 chondrosarcoma and 1 osteosarcoma) corresponding to an incidence rate of 2.1/1000 patient-years at risk. Anecdotal reports were collected regarding 2 further SPMs (a thyroid carcinoma and a myeloid leukaemia) as well as several benign tumours, including 2 mammary fibroadenomas.
Child↗
Prospective randomized comparison of two prophylactic regimens with trimethoprim-sulfamethoxazole in leukemic children: a two year study.
Between 1 July 1984 and 30 June 1986 all children treated for acute hematologic malignancy at our center were randomized to receive continuous (group A) or intermittent (3 days/week, group B) prophylaxis with trimethoprim-sulfamethoxazole (5-25 mg/kg/day/p.o.) against interstitial pneumonia with the aim of investigating if an intermittent regimen is as effective as and less toxic than a continuous regimen. The number of severe infections (group A, 17; group B, 21) and side-effects (group A, 30; group B, 34) was similar in the two groups, and compliance was also similar. We conclude therefore that neither regimen offers advantages over the other and the decision which to use should be based on cost (where regimen B has the advantage) and the children's and parents' preferences and compliance.
Acute Disease↗
Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.
One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.
Adolescent↗
Cardiac relapses in myeloid leukemia: case report and review of the literature.
Granulocytic sarcoma (GS) is a localized destructive tumor mass composed of immature cells of the granulocytic series, occurring before, concomitantly, or after the overt development of acute or chronic myelogenous leukemia. Although this tumor is known to occur in almost every site of the body, cardiac involvement is rare. We report a case of a 12-year-old female previously treated for 28 months with chemotherapy for acute promyelocytic leukemia, who presented with GS in the left mastoid 3 months after discontinuing treatment. The patient was treated with local radiotherapy only. Thirty months later she presented with heart failure, the result of a right-sided intracardiac mass, while in continuous hematological remission of the primary disease and off therapy. The cardiovascular, hematological, and postmortem findings are described and the literature is reviewed. This is the first clinicopathologic report of GS involving the heart in which the echocardiographic and pathologic findings are detailed.
Cardiomyopathies↗
Myelodysplastic syndromes in childhood. Report of 21 patients from Italy and West Germany.
Nine Italian and 12 German children fulfilled the criteria of myelodysplastic syndromes (MDS), according to the French-American-British (FAB) classification. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Four presented with refractory anemia with excess of blasts (RAEB), 16 presented with refractory anemia with excess of blasts in transformation (RAEB-T), and 1 had chronic myelomonocytic leukemia (CMML). Dyserythropoiesis and dysgranulopoiesis were seen in all patients, and dysmegakaryopoiesis was seen in most patients. Cytogenetic studies in 13 of the 21 children showed karyotype abnormalities in 8; 5 had monosomy 7. Eleven patients were treated with intensive chemotherapy soon after diagnosis; 6 achieved complete remission (CR), and 2 of them are alive and still in complete remission after 48 and 69 months. Low-dose cytosine arabinoside (Ara-C) was given in six children without improvement. Bone marrow transplantation after progression of the disease has produced complete remission lasting 28 + months now in one of two patients. Four patients received only symptomatic treatment. The rate of 5-year survival for the total group was 20% (SD 9%). We conclude that children with MDS may benefit from more aggressive treatment, but that in general the survival rate is poor and similar to that observed in adults with the same subtypes of this disease.
Adolescent↗
Histone H1(0) is synthesized by human lymphocytic leukemia cells but not by normal lymphocytes.
Using a two-dimensional gel electrophoresis system (sodium dodecyl sulphate/acetic acid-urea-hexadecyltrimethylammonium bromide) coupled with fluorography, we investigated the synthesis of H1 isoproteins in leukemic cells obtained from peripheral blood of eight children suffering from acute lymphoblastic leukemia (ALL) (four T-ALL, three common ALL, and one B-ALL) and in normal peripheral lymphocytes. H1 was synthesized in leukemic cells but not in normal lymphocytes. Inhibition of DNA synthesis with hydroxyurea and 1-beta-D-arabinofuranosylcytosine induced an increase of relative synthesis of H1(0) in leukemic cells but did not induce any detectable synthesis of H1 in normal lymphocytes. H1(0) synthesis was also undetectable in peripheral lymphocytes of leukemic children in complete remission after chemotherapy and in lymphocytes of a homozygotic twin of a leukemic patient. H1(0) may be a marker of malignant transformation of lymphocytes and as such could be of use for early detection of relapse in patients with acute lymphocytic leukemia in apparent complete remission.
Electrophoresis↗
Italian registry of patients off therapy after childhood acute lymphoblastic leukemia. Results after first phase of data collection.
The Italian Registry of Off-Therapy patients after childhood tumors now includes 760 subjects with acute lymphoblastic leukemia. These patients were all removed from treatment by December 31, 1981, and were followed in 35 different institutions. All the children have received multiple-drug treatment, combined, in 79.7% of the cases, with cranial irradiation. Thirty-nine (5%) experienced a relapse before treatment suspension. Total duration of antileukemic therapy ranges between 18 and 131 months (median, 38). At the last updating (December 31, 1981), 699 subjects were alive, 6 were lost to follow-up, and 55 had died. Life-table analysis shows that 90.8% were alive and 77% were alive in continuous complete remission at 36 months, whereas at 66 months, the cumulative proportions were 88% and 75.5%, respectively. One hundred thirty-six of 760 relapses after therapy suspension were reported: 83 in male patients and 53 in female patients (P less than 0.01). The longest interval between relapse and treatment suspension was 64 months. Six of 55 died in continuous complete remission 3 to 44 months after treatment suspension. Five births of apparently normal babies to female patients have been reported. A general outline of the project and the future program are given.
Actuarial Analysis↗
Does hepatitis B virus cross the blood-brain barrier?
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Blood-Brain Barrier↗
Recurrences of isolated leukemic hypopyon in a child with acute lymphoblastic leukemia.
The authors report follow-up observations for a case of isolated leukemic uveopathy that was first diagnosed in an 11-year-old girl shortly after cessation of treatment for acute lymphoblastic leukemia (ALL). Prior therapy for the complication included systemic antiblastic chemotherapy and low doses of radiation (3.9 Gy) to the affected eye. In July 1979, 2 months after chemotherapy was stopped for the second time, she presented with recurrent leukemic hypopyon in the left eye and was treated again with antiblastic chemotherapy followed in 1 year by high-dose (20 Gy) local irradiation. After a third recurrence, which was diagnosed as pre-B/B-cell ALL with a variable position of maturation arrest, enucleation was performed. The patient remains in complete remission for 26+ months after an additional course of systemic chemotherapy. This case illustrates the difficulty of eradicating leukemic cells from the eye with conventional treatment but suggests that a relapse in this site is not necessarily an ominous prognostic sign.
Adult↗
Monoclonal radioimmunoassay for hepatitis B surface antigen in sera of children with acute leukemia.
Hepatitis B surface antigen (HBsAg) was detected by a monoclonal antibody radioimmunoassay in sera from five of 43 children (11.6%) with acute leukemia, who were negative by conventional assay. None of the nine positive sera had evidence of reactivity for HBV-DNA or DNA-polymerase activity. No correlation was found between the presence of HBsAg in serum by monoclonal RIA and the behaviour of anti-viral antibodies. Twenty-two children could be studied for liver HBsAg by immunofluorescence, and nine of them (40.9%) were positive, including three patients having HBsAg reactivity in serum. These data indicate that monoclonal antibodies increase the sensitivity of RIA for the detection of serum HBsAg in children with acute leukemia, who previously have frequently been found to have an atypical hepatitis B virus (HBV) serology.
Acute Disease↗
Randomized multicentric Italian study on two treatment regimens for marrow relapse in childhood acute lymphoblastic leukemia.
This paper reports the results of a multicentric randomized clinical trial on the treatment of first hematological relapse in childhood ALL. Induction treatment consisted of vincristine, adriamycin, L-asparaginase, and prednisone. Patients achieving complete remission were randomized to two maintenance regimens (A and B). Regimen A consisted of five different drug associations including VM26 and IDMTX in a sequential schedule; Regimen B was essentially classical Spiers schedule for the first year, followed by a milder treatment. Eighty-four of 102 evaluable patients (82%) achieved second complete remission. The two maintenance regimens were similar as regards duration of second complete remission (median duration A, 32 weeks; B, 37 weeks) and toxicity. Better results were obtained in patients relapsing after 12 months from suspension of treatment in first complete remission than in those relapsing within the first year off therapy (82.8% vs. 31.4%). In group A fewer CNS relapses were reported. The two regimens produced results similar to those reported by other authors. The good prognosis in patients relapsing at least 1 year after treatment suspension in first complete remission must be emphasized.
Antineoplastic Combined Chemotherapy Protocols↗
Ceftriaxone kinetics after a single intravenous dose in leukemic children with fever and granulocytopenia.
Ceftriaxone (CFX) is a new third-generation cephalosporin with interesting characteristics as regards both its antibacterial spectrum and kinetics which make it potentially useful in the empiric treatment of infections in neutropenic cancer patients. However, since its kinetic characteristics in children with leukemia are not known and its pharmacokinetics are reported to be altered in such patients, we studied ceftriaxone's activity in ten leukemic children with fever and neutropenia. Our findings seem to be confirm the potential efficacy of the drug also in this particular type of patient.
Agranulocytosis↗
Hepatitis B virus markers in children with acute leukemia: the effect of chemotherapy.
Hepatitis B virus markers were tested in the serum of 49 children with acute leukemia on clinical presentation and during subsequent chemotherapy. Hepatitis B surface antigenemia was observed in only six patients (12%), none of whom progressed to chronic infection. Chemotherapy had a marked suppressive effect on the production of antibodies to hepatitis B virus antigens and overt infection occurred in two children after suppression of protective immunity. Evidence of liver damage was frequently observed and was largely independent of serologic data. These results indicate that active immunization with hepatitis B vaccine may not find a clear place in this clinical setting.
Acute Disease↗
Growth and sexual maturation in thalassemia major.
Growth and sexual development were evaluated in 250 adolescents with beta-thalassemia major. Before transfusion hemoglobin concentration had not been less than 9.5 gm/dl in the last 5 years; desferrioxamine had been administered for 7 to 10 years, including by the subcutaneous route for 3 years. Thirty-seven percent of patients were found to be 2 SD below the mean for normal height; after age 14 years the percentage was 62% for males and 35% for females. Eighty-three percent of males and 75% of females had delayed skeletal maturation. Complete lack of pubescent changes was present in 38% of females and 67% of males aged 12 to 18 years. Only 19% of females had experienced menarche; secondary amenorrhea intervened in a third of them. A multiple regression analysis of indicators of pubertal development with age, age at first transfusion, age at splenectomy, number of transfusions, serum transaminase and ferritin, and duration and intensity of chelation therapy failed to identify the factors responsible for the variation observed in sexual maturation among patients with thalassemia.
Adolescent↗
Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.
A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.
Acute Disease↗
Urate-oxidase as hypouricemic agent in a case of acute tumor lysis syndrome.
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Acute Kidney Injury↗
Responsiveness of testis morphology to chemotherapy in childhood leukemia.
The appearance of seminiferous tubules and interstitial cells of children, aged 2.5 to 13 years, affected by acute lymphoblastic leukemia was analyzed in sections. The testicular biopsies were performed at the end of therapy (vincristine, prednisone, L-asparaginase, 6-mercaptopurine, intrathecal methotrexate), which was affected for the same period and at the same doses. Three age groups were considered (I, 2.5 to 5 years; II, 6 to 9 years; III, 12 to 13 years). Age groups I and II presented damage of some tubules (25-35%) and areas of degeneration. Histometric analysis performed for A type spermatogonial population gave a mean value corresponding to controls in age group I and a mean value significantly lower with respect to controls in age group II. Moreover, age group II presented a lack of increase in tubular cross section. These results suggest that there is a vulnerability both of whole tubules and of some areas of Sertoli cells and germ cels to cytotoxic-induced damage. Leydig cells appear to be the cells least sensitive to drugs, and hormonal data indicate that the hypothalamic pituitary function appears to be intact, despite chemotherapy. Long-term prospective studies of reproductive function in children receiving cancer chemotherapy are needed to determine the magnitude and duration of damage resulting from therapeutic treatment.
Antineoplastic Combined Chemotherapy Protocols↗