The American journal of pediatric hematology/oncology最新文献

Purpose: We report a case of adrenal cortical carcinoma in an infant, which was incidentally discovered by renal sonography after a urinary tract infection. The previous death of a sibling after rhabdomyosarcoma in infancy prompted a search for a heritable p53 tumor suppressor gene mutation in this family.

Patients and methods: Starting with frozen adrenal carcinoma tissue, polymerase chain reaction (PCR) amplification followed by direct sequencing of exons 4-8 of p53 was used to search for a mutation. When a mutation was identified in exon 6 of the tumor p53 sequence, PCR amplification and direct sequencing of exon 6 alone was then performed on DNA from peripheral blood lymphocytes (PBLs) of all immediate family members to determine whether a germline mutation was present. A different set of primers was used by a second laboratory at our institution to independently confirm the presence of the mutation in the adrenal carcinoma and in paraffin-embedded rhabdomyosarcoma tissue of the deceased sibling.

Results: A C-to-T transition was identified at a CpG site in codon 196 resulting in a change from arginine to a stop codon (CGA to TGA). The identical mutation, present as the sole p53 allele in the tumor DNA samples and in the heterozygous state with wild type p53 allele in DNA from PBLs (germline), was found in the adrenal carcinoma, the rhabdomyosarcoma, and the PBLs of the tumor-bearing child and her healthy father and 5-year-old brother. This nonsense mutation of p53 has never before been reported in the germline. The extended pedigree showed only one known additional cancer.

Conclusions: A novel germline p53 mutation was identified by investigation of a sibling pair with cancers associated with the Li-Fraumeni syndrome in a family with an otherwise negative history for cancer. The implications of this case for identification of carriers of p53 germline mutations and their clinical management are discussed.

Purpose: Infection with human parvovirus B19 is the most common cause of transient aplastic crisis in patients with chronic hemolytic anemia. Multiple reports of children with simultaneous B19 infection and thrombocytopenia as well as the known association between experimental B19 infection and thrombocytopenia prompted us to hypothesize that B19 may be associated with childhood idiopathic, or immune, thrombocytopenic purpura (ITP). Because there is a paucity of evidence regarding a viral etiology for ITP, we performed a comprehensive study to explore its possible relationship to B19 infection.

Patients and methods: Thirty-five previously healthy children with ITP were studied prospectively. Bone marrow and peripheral blood were analyzed for B19 DNA using the polymerase chain reaction (PCR). Serum was analyzed for anti-B19 immunoglobulin (Ig) M and IgG antibodies using a B19 VP1 antigen-based enzyme-linked immunosorbent assay. Fourteen healthy children served as controls for peripheral blood PCR and serologic analyses.

Results: The presenting clinical and laboratory features of the study population were typical of classic ITP. Seventeen of the 35 patients (49%) had evidence of B19 DNA in the peripheral blood, bone marrow, or both. Six of 35 (17%) had anti-B19 IgM antibodies. Eight of 35 (23%) were anti-B19 IgG seropositive. The control group had no positive PCR or anti-B19 IgM specimens.

Conclusions: Our results suggest that infection with human parvovirus B19 may be associated with childhood ITP. More investigation is warranted regarding the role of PCR methodology and serologic detection methods in defining B19 pathobiology as it relates to ITP.

Background: G-CSF has been shown to be beneficial in cyclic neutropenia when given as a daily subcutaneous injection. We investigated the usefulness of a new three-day-a-week regimen.

Methods: A ten year old boy with cyclic neutropenia was initially treated with G-CSF 7 micrograms/kg given on alternate days for seven months. He was then placed on the same dose, given three days a week. The effectiveness of these regimens were assessed by serial CBCs and by the frequency and duration of the symptoms.

Results: The mean absolute neutrophil count (ANC) increased from 1282 before therapy to 11,718/microliters on alternate day regimen and 7716/microliters on three-day-a-week regimen. The nadir ANC improved from 30/microliters before therapy to 546/microliters and 198/microliters on treatment. The duration and frequency of mouth sores were significantly less on therapy, and there was an estimated cost savings of $23,826/year on three-day-a-week regimen compared to a daily regimen.

Conclusion: The three-day-a-week G-CSF regimen is clinically effective and cost saving in the treatment of cyclic neutropenia and should be studied in a larger cohort of patients.

Purpose: We review the experience with autologous peripheral blood cell transplantation (APBCT) in children with neuroblastoma at the University of Minnesota.

Patients and methods: Aspects of peripheral blood cell collection and use in nine patients who had advanced neuroblastoma (eight Evans stage IV, 1 stage III), who were median age 4 years (range 10 months-22 years) and who were treated with high-dose chemotherapy without total body irradiation and APBCT between September 1987 and December 1989 are reviewed.

Results: A median of 4.8 x 10(8) (range 3.3-8.9) mononuclear cells per kilogram of body weight were obtained by a median of six (range four-eight) collections. In vitro assay of granulocyte-monocyte colony-forming cells (CFU-GM) demonstrated a median of 3.6 x 10(4) (range 0.7-7.8) CFU-GM/kg of body weight. After APBCT, granulocyte recovery (absolute neutrophil count > 500 x 10(6)/L) occurred at a median of 28 days (range 14-72) and platelet recovery (> 150 x 10(9)/L) occurred at a median of 34 days (range 19-202). All patients but one, who had progressive disease, were transplanted with residual disease. Immunocytological analysis of peripheral blood stem cell harvest showed the presence of circulating neuroblastoma cells in three of nine patients, all of whom had minimal marrow residual disease by biopsy. One patient is still alive with no evidence of disease after 5 years. The others died of recurrent neuroblastoma a median of 14 months (range 3-29) after transplant.

Conclusion: APBCT is safe and effective for hematopoietic reconstitution after high-dose chemotherapy, and may be useful when a bone marrow harvest cannot be performed because of prior pelvic radiation or minimal residual bone marrow metastasis. Immunocytological methods to ensure that the product is free of tumor contamination should be performed.

Purpose: The impact of megakaryocyte growth in vitro on clinical data, especially outcome, was studied in 25 consecutive children with idiopathic thrombocytopenic purpura (ITP).

Patients and methods: Twenty children with untreated de novo ITP and five children with pretreated ITP were evaluated. The number of megakaryocyte colonies (cloning efficiency), the mean cell number per colony (mitotic amplification) and the percentages of polyploid megakaryocytes after 7 and 12 days in culture (relative size of the endomitotic compartment) were determined in two separate clonal assays. The culture data were related to clinical findings and outcome of the thrombocytopenia.

Results: The mean cell number per megakaryocyte colony was significantly correlated with the observed increase in the platelet count 5 days after starting therapy (n = 23; r = 0.642), and a significant negative correlation was found between the relative size of the endomitotic compartment and the duration of thrombocytopenia after bone marrow culture analysis (n = 25; r = -0.503). If all 25 children with ITP (untreated de novo and pretreated ITP) were considered, a normal frequency of polyploid megakaryocytes was associated with a duration of ITP for < 6 months in 14 of 16 cases, whereas an impaired polyploidization predicted a persistence of ITP for > 6 months in 9 of 9 cases (p < 0.0005); if only children with untreated de novo ITP (n = 20) were considered, 13 of 15 children with a normal polyploidization had an acute course of their ITP and 5 of 5 children with an impaired polyploidization developed chronic ITP (p < 0.003).

Conclusions: The results in this small group of patients suggest that the assessment of the relative size of the endomitotic compartment after 7 and 12 days in plasma clot culture actually appears to be the best method for predicting a chronic course in children with ITP.

Purpose: Langerhans cell histiocytosis (LCH) in its disseminated form usually occurs in the very young, and has a fulminant, rapidly progressive, and fatal course despite different forms of therapy.

Patients and methods: We treated two patients, who had failed on vinblastine treatment, with i.v. etoposide (VP-16) at a dose of 150 mg/kg/day for 3 days. Patient I, 8 months of age, presented with failure to thrive and huge bilateral granulomatous lesions of the external auditory canal with erosion and extensive destruction of the petrous pyramids and mastoid area. Patient II, 20 months of age, presented with widespread purpuric skin rash, hepatosplenomegaly, and bone marrow involvement.

Results: Both patients sustained complete remission (CR) following three to six courses of VP-16 and continued to be in unmaintained CR for > 48 months from diagnosis. No major toxicity was noted.

Conclusions: Etoposide (VP-16), an epipodophyllotoxin known for its usefulness in the treatment of malignancies of the monocyte/macrophage lineage, appears to be an effective treatment for the severe multisystem (disseminated) LCH of childhood and should be strongly considered as front-line therapy for this subgroup of patients with poor prognostic factors.

Purpose: We tested the hypothesis that weight for height, a simple index of nutritional status, is related to prognosis in childhood acute lymphoblastic leukemia (ALL).

Patients and methods: The study population was composed of 78 children with ALL tested at one U.K. center on the same protocol (UKALL-X). Outcome measures were relapse/no relapse and time to first relapse. Influence of weight for height, expressed as standard deviation scores, was tested using survival analysis in a retrospective design.

Results: The weight-for-height standard deviation score had a significant influence on time until first relapse (log ranks test, p = 0.012), with the highest risk of early relapse in children at the lower end of the weight-for-height distribution.

Conclusions: The results suggest that weight for height does have an influence on outcome in ALL, but the mechanism is unclear and the finding requires confirmation by larger scale prospective studies.

Purpose: This study was undertaken to evaluate the safety and efficacy of granisetron (a 5-hydroxytryptamine. antagonist) in children with malignant disease who had previously experienced unacceptable nausea and vomiting and/or adverse effects associated with standard antiemetic therapy.

Patients and methods: Thirty children 3-18 years of age who were receiving anticancer chemotherapy were enrolled in the study. Patients received a prophylactic dose of granisetron before chemotherapy and two subsequent doses as needed. If further antiemetics were required, standard therapy was given and those patients were classified as treatment failures. Patients received granisetron during one to three cycles of chemotherapy; a total of 66 courses were given.

Results: Eighty-seven percent of patients had good control of nausea and vomiting with granisetron alone; 90% of patients elected to receive granisetron with subsequent chemotherapy. No loss of efficacy was noted with repeated cycles in 21 patients. No serious adverse events occurred.

Conclusions: Intravenous granisetron (20 micrograms/kg/dose) appears to be a safe and effective drug for pediatric patients receiving emetogenic chemotherapy.

Purpose: The purpose of this study was to characterize pain reporting among children with sickle cell anemia (SCA) experiencing painful vaso-occlusive crises. These patients were managed according to a protocol based on self-reports of pain.

Patients and methods: Seventeen children (3-18 years) with SCA (Hb SS) who were admitted for painful crisis were asked to report their pain according to a rating scale of 0-5. These pain scores were analyzed according to the Mann-Whitney method to determine differences in pain reporting among young children (3-12 years) and adolescents (13-18 years). The Kruskal-Wallis method was utilized to determine relationships between the number of painful body sites, reported pain scores, and length of hospital stay.

Results: Children (3-12 years) reported significantly less severe pain than adolescents (13-18 years) (p < 0.01). The severity of pain reported was not related to the number of painful sites. However, the length of stay was significantly longer in patients with greater numbers of painful sites (p < 0.05). Patients who reported pain scores of > 2 at 24 h had significantly longer periods of hospitalization.

Conclusion: A protocol based upon self-reports of pain was successfully utilized to provide analgesia during painful crises. There were characteristic differences between young children and adolescents in self-reporting of pain. Pain scores may be helpful in predicting length of hospitalization for painful crises.