RESUMO
Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab. In each trial, certain KIR/KIR-ligand genotypes were associated with clinical benefit for patients randomized to immunotherapy treatment (immunotherapy in COG; maintenance rituximab in ECOG) as compared to patients that did not receive the immunotherapy [isotretinoin alone (COG); no-maintenance (ECOG)]. Namely, patients with both KIR3DL1 and its HLA-Bw4 ligand (KIR3DL1+/HLA-Bw4+ genotype) had improved clinical outcomes if randomized to immunotherapy regimens, as compared to patients with the KIR3DL1+/HLA-Bw4+ genotype randomized to the non-immunotherapy regimen. Conversely, patients that did not have the KIR3DL1+/HLA-Bw4+ genotype showed no evidence of a difference in outcome if receiving the immunotherapy vs. no-immunotherapy. For each trial, HLA-Bw4 status was determined by assessing the genotypes of three separate isoforms of HLA-Bw4: (1) HLA-B-Bw4 with threonine at amino acid 80 (B-Bw4-T80); (2) HLA-B-Bw4 with isoleucine at amino acid 80 (HLA-B-Bw4-I80); and (3) HLA-A with a Bw4 epitope (HLA-A-Bw4). Here, we report on associations with clinical outcome for patients with KIR3DL1 and these separate isoforms of HLA-Bw4. Patients randomized to immunotherapy with KIR3DL1+/A-Bw4+ or with KIR3DL1+/B-Bw4-T80+ had better outcome vs. those randomized to no-immunotherapy, whereas for those with KIR3DL1+/B-Bw4-I80+ there was no evidence of a difference based on immunotherapy vs. no-immunotherapy. Additionally, we observed differences within treatment types (either within immunotherapy or no-immunotherapy) that were associated with the genotype status for the different KIR3DL1/HLA-Bw4-isoforms. These studies suggest that specific HLA-Bw4 isoforms may differentially influence response to these mAb-based immunotherapy, further confirming the involvement of KIR-bearing cells in tumor-reactive mAb-based cancer immunotherapy.
RESUMO
Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.
Assuntos
Leucemia Mieloide Aguda/genética , Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Telômero/genética , Adolescente , Criança , Pré-Escolar , Primers do DNA , Feminino , Seguimentos , Granulócitos/patologia , Humanos , Lactente , Leucócitos Mononucleares/patologia , Masculino , Mapeamento por Restrição , Telomerase/genética , Telomerase/metabolismoRESUMO
Hyperdiploidy is useful in defining histologic variants of Wilms tumor and prognosis in other childhood cancers. We describe a case of hyperdiploid favorable histology Wilms tumor (50,XY,+6,+7,+8,+10,+12,-21[2]/51,idem,+9[6]/46,XY[12]) in a 3-year-old boy, and review the literature for other hyperdiploid childhood renal lesions.
Assuntos
Aberrações Cromossômicas/genética , Diploide , Neoplasias Renais/genética , Tumor de Wilms/genética , Pré-Escolar , Transtornos Cromossômicos , Humanos , Cariotipagem , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Tumor de Wilms/patologia , Tumor de Wilms/cirurgiaRESUMO
PURPOSE: Ganglioside G(D2) is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-G(D2) monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximum-tolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting. PATIENTS AND METHODS: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1, 000/microL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 microg/m(2)/d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m(2)/d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated. RESULTS: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m(2)/d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients. CONCLUSION: ch14.18 can be administered with GM-CSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m(2)/d for 4 days when given in this schedule with GM-CSF.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Gangliosídeos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neuroblastoma/terapia , Adolescente , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/imunologia , Formação de Anticorpos/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Relação Dose-Resposta Imunológica , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Camundongos , Neuroblastoma/imunologia , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/imunologiaRESUMO
OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic splenectomy in pediatric patients with hematologic diseases. METHODS: A retrospective chart review was performed to analyze the following: indication for splenectomy, pre- and peri-operative management, surgical technique, complications, duration of hospitalization, and outcome. RESULTS: Eleven patients underwent laparoscopic splenectomy for the following indications: recurrent thrombocytopenia (<10,000) in seven with chronic immune thrombocytopenic purpura; anemia in two with hereditary spherocytosis; and hypersplenism in one and recurrent splenic sequestration in another with homozygous hemoglobin S. The six girls and five boys had a median age of 7 years. The median operative time was 180 minutes, and the median hospitalization was 72 hours. Among the patients with immune thrombocytopenic purpura (median platelet count, 153,000), those patients (n=3) with platelet counts of <100,000 did not suffer any bleeding complications. The patient with hypersplenism and homozygous hemoglobin S required a small incision in the left lower quadrant to facilitate removal of a 558-gram spleen. This patient also underwent cholecystectomy for cholelithiasis. The operative time was 295 minutes, and he was hospitalized for 5 days because of atelectasis. CONCLUSIONS: Laparoscopic splenectomy is a safe and effective procedure in children with hematological disorders.
Assuntos
Doenças Hematológicas/cirurgia , Laparoscopia , Esplenectomia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , SegurançaRESUMO
The significance of random cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL) during remission is unknown. We studied 10 of 72 consecutive ALL patients who developed cytogenetic abnormalities during clinical remission to determine their effect on remission status. The cytogenetic abnormalities occurred at a median of 14.5 months (range 5-72) from the initial diagnosis. Five abnormalities were designated as clonal (monosomy 21 in three metaphases and 64 approximately 69,XXY in three metaphases from one patient at different times, and del(20)(q12q13) in three metaphases, add(13)(q34) in two metaphases, and ?del(19)(p11) in two metaphases from three different patients). Seven abnormalities were previously described: del(5)(q12), del(5)(q33), -7, del(11)(q23), +12, and +13 each in one metaphase, and del(20)(q12q13) in three metaphases). The remaining cytogenetic abnormalities were nonclonal and random. Flow cytometry and analysis of IgH and TcR gene rearrangements showed that all evaluable patients were in immunophenotypic and molecular remission, respectively. Eight patients remain in clinical and molecular remission a median of 9 months (range 7-18) after detecting the cytogenetic abnormality, and the leukemia in two patients has relapsed. During remission, cytogenetic abnormalities may not be a harbinger of leukemia relapse in pediatric ALL; therefore, a wait-and-see approach is prudent.
Assuntos
Aberrações Cromossômicas/genética , Imunofenotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Aneuploidia , Criança , Pré-Escolar , Deleção Cromossômica , Células Clonais/imunologia , Células Clonais/metabolismo , Células Clonais/patologia , Feminino , Citometria de Fluxo , Rearranjo Gênico/genética , Rearranjo Gênico do Linfócito T , Genes de Imunoglobulinas/genética , Humanos , Lactente , Cariotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Recidiva , Indução de RemissãoRESUMO
We describe a case of pediatric acute lymphoblastic leukemia (ALL) with trisomy 5 as a sole cytogenetic abnormality. A comparison is made with the two cases of adult acute lymphoblastic leukemia with trisomy 5 in the literature. This rare cytogenetic abnormality may portend an especially poor prognosis in patients with ALL.
Assuntos
Cromossomos Humanos Par 5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Trissomia/genética , Adulto , Criança , Evolução Fatal , Feminino , Rearranjo Gênico do Linfócito B/genética , Rearranjo Gênico da Cadeia delta dos Receptores de Antígenos dos Linfócitos T , Genes de Imunoglobulinas/genética , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , PrognósticoAssuntos
Síndrome de Down/complicações , Doença de Hodgkin/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Linfonodos/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Terapia de SalvaçãoRESUMO
PURPOSE: Lymphoproliferative disorders in solid organ recipients are usually of B-cell type and have rarely been described in childhood. This study describes the development of T-cell acute lymphoblastic leukemia (ALL) in a child occurring 6 years after renal transplantation. PATIENT: An 11-year-old boy had received a renal allograft from his father at 5 years of age. He was receiving imuran, prednisone, and cyclosporin A prophylaxis for graft rejection after transplant until T-cell ALL was diagnosed. Although an acute Epstein-Barr virus (EBV) infection was noted at the time of diagnosis, the EBV genome was not detected by Southern blot analysis and polymerase chain reaction (PCR) in the leukemic cells. RESULTS: A large mediastinal mass and malignant pleural effusion were noted at diagnosis. Leukemic cells of his bone marrow and pleural fluid expressed T-cell antigens with unique cytogenetic features, including add(1)(p36.1), del(11)(q14), and monosomy 7. EBV serology was consistent with a recent infection but EBV genome was not detected by Southern blot and PCR analysis in his leukemic cells. Human T-lymphotropic virus-I (HTLV-I) antibody titer was negative. He has been on chemotherapy for 9 months, maintaining his first remission. CONCLUSIONS: Malignancies developing after renal transplantations are usually lymphoproliferative disorders and of B-cell origin. In the majority of these patients, EBV plays an etiologic role. Although adult T-cell leukemia developing during immunosuppressive treatment in renal transplant recipients has been reported, T-cell leukemia after transplant in pediatric patients has not been reported to date. This case is unique in terms of the patient's age, the T-cell immunophenotype, the cytogenetic features, and the absence of an EBV genome within the leukemic cells despite an acute EBV infection before diagnosis.
Assuntos
Transplante de Rim/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/etiologia , Neoplasias do Mediastino/etiologia , Criança , Aberrações Cromossômicas , DNA Viral/análise , Herpesvirus Humano 4/genética , Humanos , Terapia de Imunossupressão/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/virologia , MasculinoRESUMO
BACKGROUND: The outcome of patients with acute myeloid leukemia (AML) who relapse or fail to achieve an initial remission has been dismal. PROCEDURE: Fifteen pediatric patients with AML, 4 relapsed and 11 primary refractory, were reinduced with a loading bolus of 0.5 g/m2 cytarabine (ara-C) followed immediately by a continuous infusion of ara-C (130 mg/m2/day) for 72 hours, followed with four daily doses (12 mg/m2/day) of mitoxantrone. Eight of 15 patients received an additional course of amsacrine and etoposide. RESULTS: Ten of 15 (66%) achieved complete response (CR) and 3 achieved partial response (PR) (20%), with an objective response rate of 86% after ara-C/mitoxantrone. One patient died before disease assessment, and one had no response after ara-C/mitoxantrone. Pharmacokinetic studies of ara-C and ara-U were performed in 13 of 15 patients. A steady-state (Css) ara-C concentration was achieved at 2 hours after the bolus ara-C dose and was maintained up to 72 hours. The Css plasma concentrations of ara-C and ara-U averaged 10.33 +/- 0.81 microM and 139.14 +/- 17.8 microM, respectively. Also, cellular pharmacokinetic studies of ara-CTP were performed on circulating leukemic cells from 5 patients. Four patients who had a significant increase (P = 0.0041) in their Css ara-CTP concentrations achieved CR, whereas one patient with an insignificant increase achieved PR. CONCLUSIONS: Continuous infusion of ara-C followed by mitoxantrone is an active reinduction regimen in refractory or relapsed pediatric AML patients. The addition of amsacrine and etoposide did not improve the remission induction rate. Further studies are needed in a larger patient population to confirm these observations.
Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/metabolismo , Citarabina/farmacocinética , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/metabolismo , Doença Aguda , Adolescente , Amsacrina/administração & dosagem , Antimetabólitos Antineoplásicos/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Citarabina/sangue , Etoposídeo/administração & dosagem , Feminino , Humanos , Lactente , Infusões Intravenosas , Leucemia Mieloide/sangue , Masculino , Mitoxantrona/administração & dosagem , Recidiva , Indução de RemissãoRESUMO
Isochromosome 7q is a nonrandom cytogenetic abnormality in Wilms tumor. Two notable cases are described: (1) a case of bilateral Wilms tumor in which only the left-sided tumor contained isochromosome 7q and (2) a case of left-sided Wilms tumor in which the tumor contained isochromosome 7q, in addition to four other chromosomal abnormalities associated with Wilms tumor.
Assuntos
Cromossomos Humanos Par 7/genética , Isocromossomos/genética , Neoplasias Renais/genética , Tumor de Wilms/genética , Pré-Escolar , Feminino , Humanos , Cariotipagem , Masculino , Translocação GenéticaRESUMO
PURPOSE: To determine the maximum-tolerated dose (MTD) of cyclophosphamide (CTX) when administered with fixed doses of carboplatin, etoposide, and melphalan (CEM) followed by autologous hematopoietic stem-cell transplantation (HSCT) in children with recurrent or high-risk solid tumors as a consolidation chemotherapy, and to make preliminary observations on efficacy. PATIENTS AND METHODS: Twenty-seven patients with solid tumors between the ages of 2 and 21 years were enrolled. Twenty of 27 had recurrent disease, whereas seven were treated in first remission. Nine were treated with melphalan 50 mg/m2/d for 4 days, carboplatin 300 mg/m2/d for 4 days as a continuous infusion (CI), and etoposide 200 mg/m2/d for 4 days as a CI (level I). CTX 750 mg/m2/d for 4 days was added to this regimen for the next 18 patients (level II). Seven of nine patients at level I and four of 18 at level II received bone marrow (BM) only, while two of nine at level I and 14 of 18 at level II received BM plus peripheral-blood stem cells (PBSC). RESULTS: The median time to reach an absolute neutrophil count (ANC) greater than 500/microl was 12.5 and 10 days for patients who received BM only and BM plus PBSC, respectively. Three cases of grade 3 mucositis, one Candida sepsis, and two transient hypoxemias were the main nonfatal toxicities. No toxic mortality was observed among level I patients. Three of 18 (16%) level II patients, all in second CR, died of transplant-related complications. Median follow-up is 29 months. Nine died of progressive disease (one second malignancy), six relapsed and are alive with disease, and nine are in continuous CR. Among the 15 PNET/Ewing's sarcoma patients, seven are in continuous CR (three of nine in second CR/VGPR, four of six in first CR/VGPR). CONCLUSION: The addition of CTX 3 g/m2 to CEM followed by autologous HSCT as a consolidation therapy resulted in 16% toxic mortality in children with recurrent or high-risk solid tumors. Further CTX dose escalation was aborted. No common nonhematologic toxicity was identified. The event-free survival (EFS) of 66% +/- 19% at 3 years for patients with metastatic PNET/Ewing's sarcoma in first remission is encouraging. However, this is based on only six patients. Both level I and II need further exploration in high-risk pediatric solid tumors in first remission.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Transplante de Medula Óssea , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Terapia Combinada , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Análise de Sobrevida , Transplante AutólogoRESUMO
Telomerase activity and telomere length in mononuclear cells (MNCs) and granulocytes from peripheral blood (PB) and bone marrow (BM) specimens were studied in pediatric acute leukemia (ALL, n = 15; AML, n = 11) and pediatric solid tumor (ST) patients (n = 9) at diagnosis, during and after chemotherapy. In four ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were analyzed. Telomerase was evaluated using a modified telomeric repeat amplification protocol (TRAP) assay, and telomere length by terminal restriction fragment (TRF) analysis. At diagnosis, high telomerase activity was detected in MNCs from all leukemia patients, which was similar to the activity from ST biopsy specimens. This exceeded by 10- to 20-fold the activity in PB MNCs from ST patients and healthy donors (P < 0.05). Granulocyte fractions lacked telomerase activity in all groups. BM MNCs in leukemia patients revealed a four-fold higher telomerase activity than PB (P = 0.005). After induction chemotherapy and response to treatment, telomerase activity decreased to borderline or undetectable levels in PB MNCs in leukemia (P < 0.01). Average telomeres in PB MNCs from pediatric patients were significantly longer (n = 25; 10.9 kbp) than telomeres in PB and BM MNCs from adult healthy donors (7.45 kbp) (P < 0.0001). At diagnosis, telomeres were shorter from BM compared to PB specimens in leukemia (P < 0.05), and two peak TRFs were observed corresponding to the malignant and normal cell clones. With the attainment of remission, the lower TRF peak, reflecting the leukemic population, was lost. In leukemia patients, mean TRFs increased on average 2.2 kbp after induction chemotherapy, but decreased thereafter on consolidation and maintenance chemotherapy (1 kbp). This was comparable to an average telomere loss of 1.2 kbp in PB specimens from ST patients after chemotherapy. In all patients, telomere loss in granulocytes as compared to MNCs was more pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consistently and highly upregulated in BM and PB specimens in leukemia, decreased after induction therapy, and correlated with remission. BM specimens in leukemia had higher telomerase activity, probably due to the greater leukemic burden than in PB. Telomeres were significantly longer in children than in adults, but shortened as a consequence of chemotherapy with repeated cycles of hematopoietic regeneration. In acute leukemia, with the loss of the leukemic burden after induction chemotherapy, longer mean TRFs were found, a reflection of the repopulation with normal cells. Our findings suggest that telomerase activity may be useful in the management of childhood malignancies. The significance of telomere length shortening in pediatric patients undergoing chemotherapy and possible telomere regeneration after myelosuppressive treatment remain to be determined.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/enzimologia , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Telomerase/metabolismo , Telômero , Adolescente , Adulto , Células da Medula Óssea/enzimologia , Células da Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Granulócitos/enzimologia , Humanos , Lactente , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Leucócitos Mononucleares/enzimologia , Masculino , Neoplasias/sangue , Neoplasias/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Análise de Regressão , Telomerase/sangueRESUMO
PURPOSE: This report describes a female infant with stage 4 multifocal ganglioneuroblastoma with gastric involvement. PATIENT: The patient had a right cervical tumor, a left posterior mediastinal tumor, bilateral adrenal tumors, and bony and bone marrow metastases. The tumor cells were diploid and lacked N-myc gene amplification. The gastric involvement, which did not produce clinical symptoms, was only detected by meticulous exploration during laparotomy. RESULTS: Our patient achieved only a partial response to alternating cycles of cyclophosphamide, vincristine, and adriamycin; and etoposide and cisplatin. She currently has stable, unresectable disease with elevated catecholamines. CONCLUSIONS: Multifocal ganglioneuroblastomas may arise from either neuroblastic rests or aberrant deposits of neuroblasts. The latter mechanism may have accounted for our patient's gastric tumor. Patients with multifocal ganglioneuroblastomas warrant meticulous radiographic and surgical evaluation to completely document the full extent of disease, and to ensure appropriate staging and therapy.
Assuntos
Ganglioneuroblastoma/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Gástricas/patologia , Feminino , Mucosa Gástrica/patologia , Humanos , LactenteRESUMO
Selective 5-HT3 receptor antagonists such as ondansetron are potent antiemetics for chemotherapy-induced emesis. Ondansetron has been shown to be highly effective in preventing nausea and vomiting in children treated with chemotherapy and/or radiotherapy. However, its high cost may limit its application. A "physician profile" provided by the hospital pharmacy and a questionnaire survey conducted amongst the attending physicians of the hematology/oncology division of a children's hospital showed wide variation in ondansetron use. This variation was evident for both the indications of use and the schedule of administration. Moreover, 80% of the physicians were not aware of the actual cost of ondansetron. In order to reduce this variation, which may affect the quality of care and increase costs unnecessarily, guidelines have been developed for the use of antiemetic drugs in pediatric oncology patients at this institution.
Assuntos
Antineoplásicos/efeitos adversos , Ondansetron/uso terapêutico , Vômito/prevenção & controle , Criança , Uso de Medicamentos , Humanos , Ondansetron/administração & dosagem , Reprodutibilidade dos Testes , Inquéritos e Questionários , Vômito/induzido quimicamenteRESUMO
We performed a retrospective analysis of the incidence, risk factors, and clinical outcome of hepatic veno-occlusive disease (VOD) in 50 children prepared for bone marrow transplantation with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg). The overall incidence of VOD was 28% (14/50). The incidence of VOD among patients transplanted for leukemia was 36% (14/39). In contrast, no patient transplanted for a genetic disease developed VOD. Neither patient age, sex, remission status, type of graft (i.e. allogeneic or autologous), past history of liver disease nor pretransplant liver function tests were associated with an increased risk of VOD. In addition, 23 of 50 patients had pretransplant samples available for antihepatitis C virus (HCV) testing; 3/23 were reactive (two of nine patients with VOD and one of 14 patients without VOD were positive for anti-HCV). We found a high incidence of pleural effusion in patients with VOD (7/14), an association that has previously not been described. VOD was manageable and resolved in all patients.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Hepatopatia Veno-Oclusiva/etiologia , Pré-Medicação , Adolescente , Adulto , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Feminino , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatite C/epidemiologia , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
The outcome of patients with advanced stage rhabdomyosarcoma is extremely poor, with a disease-free survival of less than 20% at 3 years. Autologous bone marrow transplantation for patients with Clinical Group IV rhabdomyosarcoma may be an effective therapy. The bone marrow involvement diagnosed by light microscopy is 29% for patients with advanced disease. The present study was performed to test the ability of 4-hydroperoxycyclophosphamide (4-HC) to eliminate clonogenic rhabdomyosarcoma cells. Four different human rhabdomyosarcoma cell lines were treated in vitro with 4-HC at a concentration of 100 micrograms/ml. Limiting dilution analysis was performed to detect surviving clonogenic tumor cells. Treatment with 4-HC resulted in 1.7-5.7 log of elimination of clonogenic tumor cells in all four cell lines. Exactly the same log tumor cell kill was obtained after mixing normal human bone marrow mononuclear cells with rhabdomyosarcoma cells. Treatment with 4-HC may be an effective method of eliminating clonogenic rhabdomyosarcoma cells ex vivo.
Assuntos
Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Ciclofosfamida/análogos & derivados , Rabdomiossarcoma/tratamento farmacológico , Ensaio Tumoral de Célula-Tronco , Ciclofosfamida/farmacologia , Relação Dose-Resposta a Droga , HumanosRESUMO
Serious infections caused by the Mycobacterium avium-intracellulare (MAI) complex have been increasingly recognized in patients with acquired immunodeficiency syndrome (AIDS). Allogeneic bone marrow transplant recipients are prone to infections caused by a wide spectrum of organisms. However, infection with MAI has been reported only once in an allogeneic bone marrow transplant setting. We describe two allogeneic bone marrow transplant recipients with severe combined immunodeficiency syndrome (SCID) in whom MAI infections occurred. Thus, MAI must be added to the list of infectious pathogens that can infect allogeneic bone marrow transplantation (BMT) recipients. Aggressive multidrug antituberculosis therapy may be of benefit in such patients.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Síndromes de Imunodeficiência/complicações , Infecção por Mycobacterium avium-intracellulare/etiologia , Tuberculose Pulmonar/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Imunidade Celular , Síndromes de Imunodeficiência/cirurgia , Terapia de Imunossupressão/efeitos adversos , Masculino , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecções Oportunistas/etiologia , Pneumonia/diagnóstico , Tuberculose Pulmonar/diagnósticoRESUMO
Pulmonary blastoma is a rare malignant tumor of the lung that has been treated primarily with surgery. The effect of combination chemotherapy has not been systematically investigated. Two pediatric cases are reported in whom combination chemotherapy consisting of vincristine, actinomycin-D, cyclophosphamide, cis-platinum, and adriamycin was successfully used. The first case, a 5-year-old boy, underwent incomplete surgical excision of the tumor followed by a 104-week course of combination chemotherapy. The second case is a 3-year-old boy who was initially treated with combination chemotherapy that resulted in an objective response; he subsequently underwent surgical excision. This intensive combination chemotherapy is effective both in inoperable tumors as initial therapy as well as a surgical adjuvant.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Torácicas/tratamento farmacológico , Neoplasias Torácicas/patologia , Vincristina/administração & dosagemRESUMO
We describe a 13-year-old black girl with sickle cell disease in whom spleen regrew after autosplenectomy during the course of a transfusion program for a cerebrovascular accident. This case illustrates the remarkable regrowth potential of the shrunken and fibrotic spleen when sickled red cells are replaced with normal cells.