Rosalia Ragusa

Assessment of the value of treatment with granulocyte colony‐stimulating factor in children with acute lymphoblastic leukemia: a randomized clinical trial

Abstract: The present trial was designed to test the effects of G‐CSF on the duration of the second phase of induction chemotherapy in children with newly diagnosed acute lymphoblastic leukemia (ALL). A total of 32 patients were assigned randomly to a group that received (14 patients; group A) or a group that did not receive (18 patients; group B) G‐CSF (10 g/kg/day subcutaneously and daily) throughout of the second phase of induction therapy. One of 14 (7.1%) patients in group A and 2 of 18 (11.1%) patients in group B completed the course of chemotherapy within the planned time. The median length of this phase was 37 days (range, 29 to 65; mean, 40; SD, 8.6) for patients in group A and 36 days (range, from 29 to 55; mean, 38; SD, 7.4) for those in group B, and the difference was not statistically significant. The number of days during which patients had granulocyte counts of less than 2 × 109/l, the number of febrile episodes of unknown origin, the number of bacterial and fungal infections and the number of days of hospitalization did not differ in a statistically significant manner between the two groups. Our data suggest that G‐CSF supportive therapy may be unnecessary in children with neutropenia of short duration, for whom the risk of infection is low.

Levels of L-asparagine in CSF after intramuscular administration of asparaginase from Erwinia in children with acute lymphoblastic leukemia.

PURPOSE As part of a study on the pharmacokinetics associated with the administration of asparaginase (ASNase) from Erwinia to the CNS, we determined the levels of asparagine in the CSF of children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Twenty children received eight standard doses of intramuscular ASNase (10,000 IU/m2) every 3 days as part of induction therapy. In the postremission phase of therapy, the children were randomized to receive either 20 courses of high-dose intramuscular ASNase (25,000 IU/m2) weekly (n = 8) or four courses of standard-dose intramuscular ASNase (10,000 IU/m2) every 3 days (n = 12). RESULTS All patients had detectable levels of L-asparagine in the CSF at the time of diagnosis. The levels of L-asparagine in CSF were undetectable in 15 of 20 (75%) and in seven of 19 (36.8%) children 3 and 5 days, respectively, after administration of standard-dose ASNase. After administration of high-dose ASNase, the levels of L-asparagine in the CSF were undetectable in five (62.5%) and two (25%) of eight children after 3 and 5 days, respectively. CONCLUSION In this study 60% to 70% and 25% to 35% of children had complete depletion of L-asparagine from the CSF after 3 and 5 days, respectively, after administration of both schedules of ASNase from Erwinia. In the remaining patients, administration of ASNase may have resulted in a suboptimal antileukemic effect at the CNS level.

Incidence and morbidity of infection by hepatitis C virus in children with acute lymphoblastic leukaemia.

A group of 90 patients with acute lymphoblastic leukaemia (ALL) in first continuous complete remission (CCR), admitted in our hospital between January 1986 and September 1992, were tested for the presence of antibodies against hepatitis C virus (HCV), antibodies against hepatitis B virus and antibodies against HIV-1 during maintenance therapy or thereafter. They were compared with a group of 71 children with other malignancies in first CCR who had been diagnosed consecutively from January 1986 to September 1992. No patient with ALL or any other malignancy was found to be positive for hepatitis B surface antigen or HIV-1. HCV-specific antibodies were detected in 28 out of 87 children (32.1%) with ALL and in 4 out of 44 patients (9%) with malignancies other than ALL who had received at least one transfusion of blood or platelets (P<0.01). HCV-specific antibodies were also detected in one out of three untransfused children with ALL but in none of the untransfused children with malignancies other than ALL. HCV-specific seropositivity influenced the management of children with ALL during maintenance therapy. In fact, as a result of abnormal liver function tests, maintenance therapy had to be suspended significantly more often in the case of HCV-seropositive patients with ALL than in HCV-seronegative ones. Despite the high morbidity during maintenance therapy, chronic liver disease (CLD) was uncommon in both groups: five children with ALL (17.2% of HCV-seropositive children) and one child with a malignancy other than ALL (25%) had CLD. If a follow up for a longer period confirms these observations the impact of HCV-related CLD on the quality of life and survival of patients with ALL or other malignancies will probably be minimal.

6-Mercaptopurine Cumulative Dose: A Critical Factor of Maintenance Therapy in Average Risk Childhood Acute Lymphoblastic Leukemia

A multivariate survival analysis including gender, age, log white blood cell (WBC) count, liver and spleen size at diagnosis, mean log WBC count during maintenance therapy, and the prescribed cumulative doses of 6-mercaptopurine (6-MP), methotrexate (MTX), vincristine (VCR), and prednisone (PDN) during maintenance therapy was performed on 53 children with average-risk acute lymphoblastic leukemia (ALL). The 6-MP cumulative dose prescribed during maintenance therapy resulted in the most important statistically significant independent prognostic factor. Patients who received less than the median cumulative dose of 6-MP (86% of planned protocol dose) fared significantly worse than the other patients, regardless of WBC count at diagnosis, gender, age, and other factors studied. Therefore, 6-MP cumulative dose during maintenance therapy may be the critical factor for effective maintenance therapy in childhood ALL.

Low-Grade Haemolysis and Assessment of Iron Status during the Steady State in G6PD-Deficient Subjects

We evaluated the iron status of 50 Sicilian patients with G6PD deficiency under steady-state conditions and compared our results with those for 50 control patients. We studied haemolysis and iron indices to evaluate the iron balance. These patients could be considered to be at risk of iron overload as a result of increased bone marrow activity. Reticulocytosis and macrocytosis with reduced levels of haptoglobin were found in the G6PD-deficient subjects, both of which are evidence of a moderate haemolysis. Iron status within the normal range, without iron overload or iron deficiency, was found.

Hodgkin's disease as a second malignant neoplasm in childhood: report of a case and review of the literature.

There is a known association between lymphoid malignancy and Hodgkins disease(HD), but the development of HD in children who have been treated for leukemia or lymphoma is very uncommon. Hodgkins disease is, after retinoblastoma, the most common primary tumor that is associated with development of second malignant neoplasm. For reasons that remain to be determined, HD is very rare as a second malignancy [1, 2, 3]. We report the caseofa eight-year-old girl whodevelopedHD 6 years aftertreatment forcommon acute lymphoblastic leukemia (ALL). This case promptedus to review the published literature for cases of secondary HD in childhood. Our experience suggests that we should follow strictly our patients with ALL and be ready to intervene with invasive diagnostic procedures at the least suspicion of a second or recurrent neoplasm. The most frequent causes of second tumors are radiotherapy, genetic susceptibility and prior treatment with certain chemotherapeutic agents, suchas nitrogen mustards. It is likely that any typeof immunodeficiency, even without symptoms, might play a role in the development of second tumors in childhood.

Diabetes Insipidus 9 Years after Cessation of Therapy for Acute Lymphoblastic Leukemia

A case of a 16-year-old who developed diabetes insipidus (DI) 9 years after cessation of therapy for ALL is reported. Because hereditary and traumatic factors are excluded as a cause of DI in this patient, possible explanations may be leukemic CNS relapse, secondary brain tumor, primitive idiopathic DI, and late sequelae of CNS radiochemotherapy.

Department of pediatric hematology and oncology, University of Catania, Italy.

We describe the organization of the Department of Pediatric Hematology and Oncology, University of Catania, an Italian pediatric center. This important University hospital is located in the Polyclinic of Catania, whose main task is to provide health care to the children living in the eastern part of Sicily. The University of Catania was founded in 1434, when Alfonso d’Aragona gave the aPlaceto that granted the city the privilege of owning a astudium generale.o The Department of Pediatric Hematology and Oncology began its activities in November 1977 and soon became one of the leading centers of pediatric hematology and oncology in Sicily and southern Italy. The present Department is a component of the Italian Association of Pediatric Hematology and Oncology (AIEOP), which was founded in 1974. The main goals of AIEOP are to organize treatment of all children with hemopathies or cancer in Italy that re ̄ ects the state of current knowledge; to establish a constructive collaboration among pediatric surgeons, radiotherapists, pathologists, and cardiologists; and to contribute to clinical research via participation in national and international trials. During the last 30 years we have seen a signi® cant increase in the survival of children with tumors: more than half of children with cancer are presently curable. However, because of the toxic effects of antineoplastic therapy and/or complications, percentages of cured patients may be low. Thus, a Pediatric Oncology Unit is of critical importance in improving the children’s health-care conditions and in decreasing the acute and negative late effects of cancer treatment in the growing population of survivors of

Unusual Cause of Sideropenic Anemia in Childhood: Solitary Gastric Polyp

Sideropenic anemia (SA) is linked to a scant supply of iron in the diet, insufficient iron absorption, or blood loss.Our report describes a case of SA in a child affected by a solitary gastric polyp. This lesion is very rare in childhood, and few cases have been reported in the literature.