RESUMO
INTRODUCTION: Treatment abandonment contributes significantly to poor survival of children with cancer in low- and middle-income countries (LMIC). In order to inform an approach to this problem, we investigated why caregivers withdraw their children from treatment. METHODS: In a qualitative study, carried out in October and November 2020, in-depth interviews were conducted with caregivers of children who had abandoned cancer treatment at the Pediatric Cancer Unit of Mbarara Regional Referral Hospital in south-western Uganda. Recorded in-depth interviews were transcribed and analyzed to identify themes of caregivers' self-reported reasons for treatment abandonment. The study was approved by the Review and Ethics Committee of Mbarara University of Science and Technology. RESULTS: Seventy-seven out of 343 (22.4%) children diagnosed with cancer abandoned treatment during the study period; 20 contactable and consenting caregivers participated in the study. The median age of the caregivers was 37 years and most (65%) were mothers. At the time of this study, eight (40%) children were alive and five (62.5%) were males; with a median age of 6.5 years. Financial difficulty, other obligations, the child falsely appearing cured, preference for alternative treatments, belief that cancer was incurable, fear that the child's death was imminent and chemotherapy side effects were the caregivers' reasons for treatment abandonment. CONCLUSIONS AND RECOMMENDATION: Seeking cancer treatment for children in Uganda is an expensive venture and treatment abandonment is mainly caused by caregivers' difficult socio-economic circumstances. This problem needs to be approached with empathy and support rather than blame.
Assuntos
Cuidadores , Gastos em Saúde , Neoplasias , Adulto , Criança , Feminino , Humanos , Masculino , Mães , Neoplasias/economia , Neoplasias/terapia , Pesquisa Qualitativa , Autorrelato , Uganda/epidemiologiaRESUMO
BACKGROUND: Fever and neutropenia is a common reason for nonelective hospitalization of pediatric oncology patients. Herein we report nearly five years of experience with a clinical pathway designed to guide outpatient management for patients who had low-risk features. PROCEDURES: Through a multidisciplinary collaboration, we implemented a clinical pathway at our institution using established low-risk criteria to guide outpatient management of pediatric oncology patients. Comprehensive chart review of all febrile neutropenia episodes was conducted to characterize outcomes of patients with low-risk febrile neutropenia following clinical pathway implementation. RESULTS: Between April 1, 2013, and October 1, 2017, there were 169 cases of febrile neutropenia managed in our Pediatric Oncology Unit. Sixty-seven (40%) of these episodes were defined as low risk and managed either entirely in the outpatient setting (41 episodes, 24%) or with a step-down strategy involving a very brief inpatient stay (26 episodes, 15%). There were no intensive care unit admissions or deaths among the low-risk patients. Of those identified as low risk, seven patients (10%) required subsequent hospitalization during the follow-up period, two for inadequate oral intake, two for persistent fevers, one for cellulitis, one for seizure unrelated to the febrile episode, and one for a positive blood culture. CONCLUSIONS: Following implementation of a clinical pathway, the majority of patients designated as low risk were managed primarily in the outpatient setting without major morbidity or mortality, suggesting that carefully selected low-risk patients can be successfully treated with outpatient management and subsequent admission if warranted.
Assuntos
Procedimentos Clínicos , Neutropenia Febril/terapia , Hospitalização , Pacientes Internados , Pacientes Ambulatoriais , Adolescente , Criança , Pré-Escolar , Feminino , Febre de Causa Desconhecida/terapia , Humanos , Masculino , Neoplasias/terapiaRESUMO
Epstein-Barr virus-related lymphoproliferative disease (EBV-LPD) rarely occurs in patients with acute lymphoblastic leukemia (ALL), who have not received hematopoietic transplantation. We describe EBV-LPD manifesting as facial lesions in two children with ALL in remission. One patient was a 16-year-old male with T-cell ALL with an EBV-positive angiocentric polymorphous lip lesion presenting as right-sided facial swelling. The other patient was a 12-year-old male with B-cell ALL with an EBV-positive polymorphous lymphoplasmacytic infiltrate presenting as bilateral dacryoadenitis. Neither patient had known primary immunodeficiencies. Both cases improved with immunosuppressant de-escalation. These cases suggest that immunosuppression induced by maintenance chemotherapy is sufficient to promote EBV-LPD.
Assuntos
Dacriocistite/etiologia , Infecções por Vírus Epstein-Barr/complicações , Transtornos Linfoproliferativos/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Criança , Humanos , MasculinoRESUMO
Patient-specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French-British-American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease (MRD) was assessed by real-time polymerase chain reaction at the end of induction (EOI) and consolidation (EOC). Seventy per cent (7/10) and 71% (5/7) were MRD-positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/sangue , Linfoma de Burkitt/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Quimioterapia de Consolidação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasia Residual , Projetos Piloto , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Children and adolescents with Burkitt Lymphoma (BL) and combined central nervous system (CNS) and bone marrow involvement still have a poor prognosis with chemotherapy alone. We therefore investigated in children and adolescents with bone marrow (≥25% blasts) and/or CNS-positive Burkitt lymphoma the chemoimmunotherapy combination of rituximab (375 mg/m(2) ) and the standard chemotherapy arm of our previously reported French-American-British (FAB) Lymphome Malins de Burkitt (LMB) 96 trial. Central pathological and cytogenetic characterization was also performed. There were 40 evaluable patients with Burkitt histology (25 with leukaemia and 15 with CNS disease ± leukaemia). The chemoimmunotherapy regimen was well tolerated. The incidence of grade III/IV mucositis during induction cycles with combined chemotherapy and rituximab was 31% and 26%, respectively. The 3-year event-free survival (EFS)/overall survival (OS) was 90% (95% confidence interval [CI], 76-96%) in the entire cohort and 93% (95% CI, 61-99%) in patients with CNS disease. Based on the results of this trial, an international randomized study of FAB/LMB 96 chemotherapy ± rituximab for high-risk patients is currently under investigation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Adolescente , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Linfoma de Burkitt/genética , Criança , Quimioterapia de Consolidação , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Genes myc , Humanos , Imunoterapia , Infusões Intravenosas , Estimativa de Kaplan-Meier , Linfoma de Células B/genética , Quimioterapia de Manutenção , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Indução de Remissão , Rituximab , Tiflite/induzido quimicamente , Vincristina/administração & dosagem , Vincristina/efeitos adversosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Criança , Feminino , Humanos , Imunoterapia/métodos , Injeções Espinhais , Estimativa de Kaplan-Meier , Masculino , Rituximab/administração & dosagem , Resultado do TratamentoRESUMO
Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.
Assuntos
Proliferação de Células , Rearranjo Gênico/genética , Linfonodos/patologia , Linfoma Folicular/genética , Linfoma Folicular/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Antígeno Ki-67/metabolismo , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Optimal therapy for children and adolescents with advanced stage anaplastic large cell lymphoma (ALCL) is unknown. ANHL0131 examined whether a maintenance regimen including vinblastine compared to the standard APO (doxorubicin, prednisone, vincristine, methotrexate, 6-mercaptopurine) regimen would result in superior event-free survival. PROCEDURE: One hundred and twenty five eligible patients were enrolled. Induction was identical for both arms. Post induction patients were randomized to receive APO with vincristine every 3 weeks or a regimen that substituted vincristine with weekly vinblastine (APV). RESULTS: There was no difference between the patients randomized to the APO versus APV arms in either event free survival (EFS) or overall survival (OS) (three year EFS 74% vs. 79%, P = 0.68 and three years OS of 84% vs. 86%, P = 0.87, respectively). Patients in the APV arm required dose reduction secondary to myelosuppression and had a higher incidence of neutropenia as well as infection with neutropenia compared to those in the APO arm (P < 0.001, P = 0.019, respectively). CONCLUSIONS: Treatment with weekly vinblastine instead of every three week vincristine as part of multi-agent maintenance therapy did not result in improvement in EFS or OS. Weekly vinblastine was associated with increased toxicity. (ClinicalTrials.gov Identifier NCT00059839).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Linfoma Anaplásico de Células Grandes/mortalidade , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vincristina/administração & dosagem , Adulto JovemRESUMO
The Children's Oncology Group's A5971 trial examined central nervous system (CNS) prophylaxis and early intensification in paediatric patients diagnosed with CNS-negative Stage III and IV lymphoblastic lymphoma. Using a 2 × 2 factorial design, the study randomized patients to Children's Cancer Group (CCG) modified Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukaemia (ALL) regimen with intensified intrathecal (IT) methotrexate (MTX) (Arm A1) or an adapted non-Hodgkin lymphoma/BFM-95 therapy with high dose MTX in interim maintenance but no IT-MTX in maintenance (Arm B1). Each cohort was randomized ± intensification (cyclophosphamide/anthracycline) (Arms A2/B2). For the 254 randomized patients, there was no difference in 5-year event-free survival (EFS) for the four arms: Arm A1, 80% [95% confidence interval (CI) 67-89%] and Arm A2, 81% (95% CI 69-89%); Arm B1, 80% (95% CI 68-88%) and Arm B2, 84% (95% CI 72-91%). The cumulative incidence of CNS relapse was 1·2%. Age <10 years and institutional imaging response at 2 weeks was associated with improved outcomes (P < 0·001 and P = 0·014 for overall survival). CNS positive patients (n = 12) did poorly [5-year EFS of 63% (95% CI 29-85%)]. For CNS-negative patients, there was no difference in outcome based on CNS prophylaxis (IT-MTX versus HD-MTX) or with intensification.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/prevenção & controle , Neoplasias do Sistema Nervoso Central/secundário , Criança , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaAssuntos
Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Janus Quinases/metabolismo , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esplenomegalia/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Humanos , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/etiologia , Esplenomegalia/metabolismo , Esplenomegalia/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The outcome of treatment for pediatric Hodgkin lymphoma (HL) is excellent using chemotherapy and radiation. However, a minority of patients will relapse after treatment, but additional therapy achieves durable second remission in many cases. The optimal surveillance strategy after modern therapy for HL has not been well defined. PROCEDURES: We reviewed the outcomes of pediatric patients with HL treated between 1990 and 2006 to determine the primary event that led to the detection of relapse. We determined the probability of relapse detection by routine follow-up procedures, including history, physical examination, laboratory tests, and imaging, and determined the impact of each of these screening methods on the likelihood of survival after relapse. RESULTS: Relapse occurred in 64 of 402 evaluable patients (15.9%) at a median of 1.7 years from the time of diagnosis. The majority of relapses (60%) were diagnosed at a routine visit, and patient complaint was the most common initial finding that led to a diagnosis of relapse (47% of relapses). An abnormal finding on physical examination was the primary event in another 17% of relapses, and imaging abnormalities led to the diagnosis in the remaining 36%. Laboratory abnormalities were never the primary finding. The method of detection of relapse and timing (whether detected at a routine visit or an extra visit) did not impact survival. CONCLUSIONS: In pediatric HL, most relapses are identified through history and physical examination. Frequent imaging of asymptomatic patients does not appear to impact survival and is probably not warranted.
Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Relapse remains the leading cause of death in patients with acute myeloid leukaemia (AML). Relatively few new chemotherapy agents have been proven to be effective in this population. We report on a Phase 2 clinical trial using the novel combination of 2-chlorodeoxyadenosine (2-CDA) (8 mg/m² per d x 5 d) plus idarubicin (Ida) (10 mg/m² per d x 3 d). The study involved 109 paediatric patients with AML at first relapse, of whom 104 were available for analysis. The overall response rate was 51% (complete response [CR] + partial response) with a CR rate of 46%. 2-year event-free survival (EFS) and overall survival (OS) were 20% and 26%. The only significant variable in determining response, EFS and OS was duration of initial remission, with patients who had an initial remission >1 year having much worse outcomes overall (response rate 74% vs. 25%, EFS 8% vs. 37% and OS of 16% vs. 39%, P < 0.01 for all). There was an acceptable toxicity profile with one neurological event and no cardiac events observed. The most common grade 3-4 toxicities observed were neutropenia (59%) and thrombocytopenia (68%). This study demonstrated that the novel combination of 2-CDA/Ida was effective and should be considered for incorporation in front line therapy for children with AML.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzodiazepinas/administração & dosagem , Diazepam/análogos & derivados , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Diazepam/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Recidiva , Adulto JovemRESUMO
KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8;21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Ligação ao Core/genética , Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Éxons/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Mutação , Prevalência , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Translocação Genética , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Localized lymphoblastic lymphoma (LL) is rare in pediatric patients. We report the 5-year event-free survival (EFS) and overall survival (OS) for children and adolescents with localized LL treated on a uniform regimen based on Children's Cancer Group (CCG) leukemia therapy (COG A5971). PROCEDURE: From June 2000 to October 2005, the study enrolled 60 patients >12 months old with Murphy stages I or II LL. Central review confirmed 56 eligible patients. Treatment consisted of 24 months of CCG BFM without day 28 intrathecal methotrexate in maintenance therapy or prophylactic cranial radiation. RESULTS: Most patients had pre-B immunophenotype (75%). At a median follow-up of 5.9 years (range 1.4-9.3 years), the 5-year EFS was 90% [95% confidence interval (CI), 78-96%] and the 5-year OS was 96% (95% CI, 84-99%). Stage (I vs. II), immunophenotype, elevated LDH > institutional normal, or primary site did not impact outcome. Five relapses occurred-none in the CNS and none in patients with pre-T lymphoblastic disease. Patients tolerated treatment well with no toxic deaths. CONCLUSION: Outcomes of pediatric patients with localized LL treated with 2 years of intensive acute lymphoblastic leukemia (ALL)-type therapy was excellent and is similar to the outcome for standard risk ALL treated less intensively. CNS prophylaxis was adequate with limited intrathecal methotrexate and no radiation. Future studies should identify biologic prognostic factors or biomarkers for pediatric patients with LL, explore less intensive treatment for patients with localized disease, and explore novel immunophenotype directed therapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/uso terapêutico , Daunorrubicina/uso terapêutico , Intervalo Livre de Doença , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisona/uso terapêutico , Recidiva , Vincristina/uso terapêuticoRESUMO
CONTEXT: More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. OBJECTIVE: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. DESIGN, SETTING, AND PATIENTS: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. INTERVENTIONS: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. MAIN OUTCOME MEASURES: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. RESULTS: Two-year event-free survival was 90.8% (95% CI, 84.7%-96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. CONCLUSIONS: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00145600.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Náusea/induzido quimicamente , Neuralgia/induzido quimicamente , Neutropenia/induzido quimicamente , Prednisona/administração & dosagem , Resultado do Tratamento , Vimblastina/administração & dosagem , Vômito/induzido quimicamente , Adulto JovemRESUMO
BACKGROUND: Valspodar, a non-immunosuppressive analog of cylosporine, is a potent P-glycoprotein (MDR1) inhibitor. As MDR1-mediated efflux of chemotherapeutic agents from leukemic blasts may contribute to drug resistance, a phase 1 study of valspodar combined with mitoxantrone and etoposide in pediatric patients with relapsed or refractory leukemias was performed. PROCEDURE: Patients received a valspodar-loading dose (2 mg/kg) followed by a 5-day continuous valspodar infusion (8, 10, 12.5, or 15 mg/kg/day) combined with lower than standard doses of mitoxantrone and etoposide. The valspodar dose was escalated using a standard 3 + 3 phase I design. RESULTS: Twenty-one patients were evaluable for toxicity and 20 for response. The maximum tolerated dose (MTD) of valspodar was 12.5 mg/kg/day, combined with 50% dose-reduced mitoxantrone and etoposide. The clearance of mitoxantrone and etoposide was decreased by 64% and 60%, respectively, when combined with valspodar. Dose-limiting toxicities included stomatitis, ataxia, and bone marrow aplasia. Three of 11 patients with acute lymphoblastic leukemia (ALL) had complete responses while no patient with acute myeloid leukemia (AML) had an objective response. In vitro studies demonstrated P-glycoprotein expression on the blasts of 5 of 14 patients, although only 1 had inhibition of rhodamine efflux by valspodar. CONCLUSIONS: While this regimen was tolerable, responses in this heavily pretreated population were limited to a subset of patients with ALL.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Ciclosporinas/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/sangue , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclosporinas/administração & dosagem , Ciclosporinas/efeitos adversos , Ciclosporinas/farmacocinética , Resistência a Múltiplos Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Etoposídeo/administração & dosagem , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Dose Máxima Tolerável , Mitoxantrona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Terapia de Salvação , Adulto JovemRESUMO
BACKGROUND: This report focuses on the children enrolled on the first North American Intergroup study of APL (INT0129). This study was designed to compare the rates of CR, disease-free survival (DFS), overall survival (OS) and toxicity of therapy with all-trans-retinoic acid (ATRA) for remission induction and/or maintenance compared to conventional chemotherapy in patients with previously untreated APL. PROCEDURE: Fifty-three patients who were documented to have the t(15;17) translocation were able to be evaluated for toxicity of treatment, outcome of induction, and survival. RESULTS: The overall CR rate was 81%. The estimated 5-year DFS from time of CR was 41% for all patients. The estimated 5-year OS for all patients from entry into the study was 69%. The 5-year DFS from time of CR for patients who were randomized to ATRA for induction or maintenance or both was 48% compared to 0% for patients who never received ATRA (P < 0.0001). CONCLUSIONS: The most important finding of our study is that a significant DFS advantage exists for children with APL who received ATRA during induction or maintenance or both compared to children who received no ATRA. Furthermore, remissions in these children appear durable as the OS rates are stable at 10 years.
Assuntos
Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/administração & dosagem , Adolescente , Criança , Pré-Escolar , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Lactente , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/mortalidade , Masculino , Indução de Remissão/métodos , Análise de Sobrevida , Resultado do Tratamento , Tretinoína/toxicidadeRESUMO
BACKGROUND: To estimate the response rate and therapy related toxicities of the anti-CD20 monoclonal antibody rituximab when combined with chemotherapy including ifosfamide, carboplatin, and etoposide (ICE) in patients with relapsed and refractory B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia (B-ALL). METHODS: Patients received rituximab and ICE for 1-3 cycles, depending upon response. Rituximab (375 mg/m(2)) was given on day 1 and 3 of each cycle (day 1 only for cycle 3), with ifosfamide (3,000 mg/m(2)) and etoposide (100 mg/m(2)) given on days 3, 4, and 5 and carboplatin (635 mg/m(2)) given on day 3 only. RESULTS: Twenty-one patients were enrolled, of whom 20 were eligible and evaluable. Although hematologic toxicities were common, only one patient was removed from study due to prolonged myelosuppression. Toxicities related to infusions of rituximab were frequent but manageable. Of the six eligible patients with diffuse large B-cell lymphoma, three achieved complete remission (CR), one had stable disease (SD), and two had progressive disease (PD). Of the 14 eligible patients with Burkitt lymphoma and B-ALL, there were four complete responses (CR), five partial responses (PR), one SD, and four with PD. Thus, the CR/PR rate for the entire group was 12/20 (60%). Following completion of protocol therapy six patients were able to proceed to consolidation with high-dose therapy and stem cell rescue. CONCLUSIONS: The combination of rituximab and ICE chemotherapy was associated with an encouraging objective response (OR) rate and an acceptable toxicity profile.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia de Células B/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Recidiva , Indução de Remissão , Rituximab , Terapia de Salvação , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Emergency department (ED) utilization is a major driver of cost. Specialist physicians have an important role in addressing ED utilization, especially at tertiary medical centers that treat highly specialized patients. We analyzed if reporting of ED utilization to pediatric specialist physicians can decrease ED visits. METHODS: Physicians within pediatric neurology, hematology and oncology, infectious diseases, and pulmonary divisions received their ED use reports. By using control charts, we examined if this intervention decreased the rate of ED utilization. RESULTS: Overall, for the 4 divisions, specialty-related ED utilization decreased significantly during all hours, weekdays, and office hours. This was in the setting of ED utilization increasing for all diagnoses ED visits. Pediatric ED volume did not change during the study period. CONCLUSIONS: Physician-level reporting of ED utilization was associated with a reduction in ED use by patients managed by our pediatric specialists.