RESUMO
PURPOSE: We evaluated the outcome of children (<15 years) versus that of adolescents and young adults (AYA; 15-≤ 21 years) treated for Hodgkin lymphoma (HL) in two Pediatric Oncology Group/Children's Oncology Group clinical trials, P9425 and P9426, that used dose-dense, response-based chemotherapy and reduced dose radiotherapy. PATIENTS AND METHODS: Subjects 21 years or younger with HL were eligible for these studies. Subjects with low-risk (stages IA, IIA, and IIIA1) without large mediastinal adenopathy biopsy-proven HL, eligible for P9426, were treated with two to four 28-day cycles of doxorubicin, bleomycin, vincristine, and etoposide (ABVE) chemotherapy and 25.5 Gy of involved field radiotherapy. Subjects with intermediate-risk (stages IB, IIA, IIIA1 with large mediastinal adenopathy, and IIIA2) and high-risk (stages IIB, IIIB, and IV) biopsy-proven HL, eligible for P9425, were treated with three to five 21-day cycles of ABVE plus prednisone and cyclophosphamide (ABVE-PC) chemotherapy and 21 Gy of involved region radiotherapy. We compared the 5-year event-free survival (EFS), based on Kaplan-Meier product-limit method, of children versus that of AYA. RESULTS: Four hundred seventy-one subjects were enrolled on P9425 and P9426 combined. Of these subjects, 203 were AYA, 104 with intermediate and high-risk HL, and 99 with low-risk HL. The 5-year EFS of children did not significantly differ from that of AYA (85.9 vs. 87.1%) with a median follow up of 7.7 years (P = 0.51). CONCLUSION: Given the equivalent and excellent results of therapy, HL represents an opportunity for adult and pediatric cancer treatment collaborative groups to jointly design clinical trials targeted to AYA. These trials should focus on both treatment efficacy and the quality of life of AYA while receiving chemotherapy and in reduction of long-term side effects in the survivorship years.
Assuntos
Doença de Hodgkin/tratamento farmacológico , Adolescente , Criança , Protocolos Clínicos , Feminino , Doença de Hodgkin/mortalidade , Humanos , Masculino , Adulto JovemRESUMO
Risk-adapted, response-based therapies for pediatric Hodgkin lymphoma have resulted in 5-year survival exceeding 90%. Although high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) are considered standard for most patients with relapsed or refractory Hodgkin lymphoma, a subset of children with low risk relapse do not require AHSCT for cure. Currently there are no widely accepted criteria defining who should receive standard dose chemotherapy and/or radiotherapy, nor is there a standardized treatment regimen. We propose a risk-stratified, response-based algorithm for children with relapsed or refractory Hodgkin lymphoma that is based on a critical appraisal of published outcomes and prognostic factors.
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Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Terapia Combinada , HumanosRESUMO
Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed ≥2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.
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Transtornos Cognitivos/induzido quimicamente , Leucoencefalopatias/induzido quimicamente , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/patologia , Feminino , Humanos , Lactente , Testes de Inteligência , Leucoencefalopatias/epidemiologia , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Masculino , Metotrexato/administração & dosagem , Testes Neuropsicológicos , Prevalência , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. RESULTS: Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. CONCLUSIONS: Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/administração & dosagem , Criança , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Teniposídeo/administração & dosagemRESUMO
Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy seen in childhood and frequently occurs in the head and neck region. Pediatric head and neck RMS is often misdiagnosed as common benign conditions. Here we describe an embryonal RMS that presented as a peritonsillar abscess (PTA). Due to an incorrect initial diagnosis and lack of imaging, the patient received unnecessary medical therapy and diagnosis of RMS was delayed.
Assuntos
Abscesso Peritonsilar/diagnóstico , Neoplasias Faríngeas/diagnóstico , Rabdomiossarcoma Embrionário/diagnóstico , Pré-Escolar , Diagnóstico Tardio , Diagnóstico Diferencial , Evolução Fatal , Humanos , Masculino , Neoplasias Faríngeas/terapia , Rabdomiossarcoma Embrionário/terapiaRESUMO
BACKGROUND: Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes. METHODS: Protocol P9426, a response-dependent and reduced treatment for low risk Hodgkin lymphoma (stages I, IIA, and IIIA(1) ) was designed in 1994 based on a previous pilot project. Patients were enrolled from October 15, 1996 to September 19, 2000. Patients were randomized to receive or not receive dexrazoxane and received two cycles of chemotherapy consisting of doxorubicin, bleomycin, vincristine, and etoposide. After two cycles, patients were evaluated for response. Those in complete response (CR) received 2,550 cGy of involved field radiation therapy (IFRT). Patient with partial response or stable disease, received two more cycles of chemotherapy and IFRT at 2,550 cGy. RESULTS: There were 294 patients enrolled, with 255 eligible for analysis. The 8-year event free survival (EFS) between the dexrazoxane randomized groups did not differ (EFS 86.8 ± 3.1% with DRZ, and 85.7 ± 3.3% without DRZ (P = 0.70). Forty-five percent of patients demonstrated CR after two cycles of chemotherapy. There was no difference in EFS by histology, rapidity of response, or number of cycles of chemotherapy. Six of the eight secondary malignancies in this study have been previously reported. CONCLUSIONS: Despite reduced therapy and exclusion of most patients with lymphocyte predominant histology, EFS and overall survival are similar to other reported studies. The protocol documents that it is safe and effective to reduce therapy in low-risk Hodgkin lymphoma based on early response to chemotherapy with rapid responding patients having the same outcome as slower-responding patients when given 50% of the chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Bleomicina/administração & dosagem , Criança , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Razoxano/administração & dosagem , Indução de Remissão , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto JovemRESUMO
Current treatment strategies for Hodgkin lymphoma result in excellent survival but often confer significant long-term toxicity. We designed ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of long-term sequelae by response-based reduction of cumulative chemotherapy. Efficient induction of early response by dose-dense drug delivery supported an early-response-adapted therapeutic paradigm. The 216 eligible patients were younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles received 21 Gy radiation to involved regions; RER was documented in 63% of patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the slow early responders (P = .85). Only 1% of patients had progressive disease. Five-year overall survival was 95%. With this regimen, cumulative doses of alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen that provides outstanding event-free survival/overall survival with short duration, early-response-adapted therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Adolescente , Adulto , Bleomicina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Prednisolona/administração & dosagem , Dosagem Radioterapêutica , Taxa de Sobrevida , Fatores de TempoAssuntos
Bacteriemia/sangue , Bacteriemia/diagnóstico , Sangue/microbiologia , Feminino , Humanos , MasculinoRESUMO
PURPOSE: In pediatric patients with acute lymphoblastic leukemia (ALL), the optimal time for central venous line (CVL) insertion and the optimal type of CVL (internal v external) is unclear. This study was undertaken to compare complication rates between early versus late line insertion, and between internal versus external lines in children with lesser risk ALL. PATIENTS AND METHODS: We performed a retrospective analysis of patients enrolled onto Pediatric Oncology Group (POG) protocol 9201. Data regarding demographics, CVL types and insertion dates, blood counts, and complications were reviewed through week 25 of therapy. RESULTS: Of 697 patients enrolled onto POG protocol 9201, 362 patients had sufficient data for analysis. When compared to late line placement (> day 15 of induction), early CVL placement (= day 15 of induction) was associated with an increased risk of having a positive blood culture (odds ratio, 2.2; 95% CI, 1.0 to 5.0; P = .05). When compared with internal CVLs ("ports"), external CVLs were associated with a positive blood culture (odds ratio, 3.1; 95% CI, 1.3 to 7.5; P = .01), thrombosis (odds ratio, 3.9; 95% CI, 1.5 to 10.3; P = .006), and CVL removal (odds ratio, 5.6; 95% CI, 2.7 to 11.6; P < .001). CONCLUSION: In pediatric patients with lesser risk ALL, internal lines (ports) should be the preferred CVL type due to a lower risk of infectious and thrombotic complications. In addition, CVLs placed early in induction are associated with a higher risk of positive blood culture than those placed later in induction.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cateterismo Venoso Central/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Cateterismo Venoso Central/métodos , Pré-Escolar , Feminino , Humanos , Infecções , Masculino , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Trombose/etiologia , Fatores de TempoRESUMO
Klinefelter syndrome was first described in 1942 as an endocrine disorder characterized by gynecomastia, hypogonadism, small testes, and elevated levels of follicle-stimulating hormone. An extra X chromosome (i.e., 47,XXY) was subsequently demonstrated in these patients and an increased incidence of leukemia and lymphoma has been described. We report a retrospective study of a series of unselected patients with Klinefelter syndrome diagnosed by cytogenetic studies and the occurrence of hematologic malignancies. The literature is also reviewed.
Assuntos
Neoplasias Hematológicas/genética , Síndrome de Klinefelter/genética , Leucemia/genética , Linfoma/genética , Adulto , Humanos , Incidência , Cariotipagem , Leucemia/epidemiologia , Linfoma/epidemiologia , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis. STUDY DESIGN: Charts of all (N = 30) patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30. RESULTS: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care). All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history. CONCLUSIONS: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.
RESUMO
PURPOSE Children with Hodgkin's lymphoma (HL) routinely undergo surveillance computed tomography (CT) imaging for up to 5 years after therapy, resulting in cost and radiation exposure, without clear benefit. The objective of this study was to determine the contribution of surveillance CT, as compared with clinical findings, to detection of disease recurrence. PATIENTS AND METHODS Two hundred sixteen patients, age ≤ 21 years old, were treated on the multicenter Pediatric Oncology Group 9425 trial. Data for patients who experienced relapse were retrospectively reviewed to determine whether imaging or clinical events prompted suspicion of disease recurrence. Correlation was made to disease stage, time to recurrence, relapse site, and overall survival (OS). Results With a median follow-up time of 7.4 years, 25 (11.6%) of 216 patients had experienced a relapse, of whom 23 experienced local relapse. Median time to relapse was 7.6 months (range, 0.2 to 48.9 months). Nineteen relapses (76%) were detected based on symptoms, laboratory or physical examination findings, and two relapses (8%) were detected by imaging within the first year after therapy. Only four patients (16%) had their recurrence detected exclusively by surveillance imaging after the first year. Six deaths occurred, all in patients who experienced relapse within the first year after therapy. No patient with a recurrence after 1 year off treatment has died, regardless of how the recurrence was detected. CONCLUSION The majority of pediatric HL relapses occurred within the first year after therapy or were detected based on change in clinical status. Detecting late relapse, whether by imaging or clinical change, did not affect OS. These findings indicate that CT is overused for routine surveillance of patients with HL.
Assuntos
Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Vigilância da População , Tomografia Computadorizada por Raios X , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Imagem Multimodal , Estadiamento de Neoplasias , Vigilância da População/métodos , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years. RESULTS: Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (+/- SE) for patients with TEL rearrangements was 86% +/- 2%, compared with 72% +/- 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002). CONCLUSION: We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Regulação Leucêmica da Expressão Gênica , Rearranjo Gênico , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Adulto , Medula Óssea/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
The treatment for favorable-prognosis stage I and II Hodgkin's lymphoma has evolved over the past several years. Studies have attempted to reduce long-term treatment-related side effects, such as second malignancies and cardiac toxicity, through reduced chemotherapy or reduced radiotherapy. Randomized trials have compared radiation therapy alone with combined-modality therapy (chemotherapy followed by involved-field radiotherapy). Recent and ongoing trials have evaluated the optimal regimen and number of cycles of chemotherapy and the optimal radiotherapy dose and field size as part of combined-modality therapy, as well as the elimination of radiation therapy. Combined-modality therapy represents the current standard of care for most patients with favorable-prognosis early-stage Hodgkin's lymphoma. Chemotherapy alone could also be an option for selected patients who are at low risk for relapse and high risk for late effects from radiotherapy. This article reviews recent and ongoing studies on treatment for favorable-prognosis early stage Hodgkin's lymphoma. Representative clinical cases are presented, with treatment recommendations from an expert panel of radiation oncologists and medical oncologists.
Assuntos
Ensaios Clínicos como Assunto , Atenção à Saúde/normas , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Guias de Prática Clínica como Assunto , Radiologia/normas , Humanos , Prognóstico , Estados UnidosRESUMO
The diagnosis of Burkitt lymphoma by thoracentesis has been rarely reported in the literature, particularly in children. From 1995 to 2004, we diagnosed six pediatric patients with mature B-cell neoplasms using thoracentesis as the initial diagnostic procedure. The cytology, immunophenotyping, and cytogenetic results of the pleural fluid cells were consistent with mature B-cell malignancies. We conclude that thoracentesis for the diagnosis of Burkitt lymphoma in children is safe, fast, and accurate. It should be strongly considered as an initial diagnostic procedure for pediatric patients with pleural effusions who are suspected of having B-cell malignancies.
Assuntos
Linfoma de Burkitt/diagnóstico , Paracentese , Derrame Pleural/patologia , Adolescente , Linfoma de Burkitt/terapia , Criança , Pré-Escolar , Técnicas Citológicas , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Cirurgia TorácicaRESUMO
The Pediatric Oncology Group 9203 pilot protocol was designed to determine the feasibility of delivering 29 biweekly doses of polyethylene glycol (PEG)-L-asparaginase, on a backbone of intensive multiagent antimetabolite-based consolidation and maintenance in higher risk B-precursor acute lymphoblastic leukemia. Between June 1992 and August 1993, 34 patients were enrolled on this limited institution pilot. The 5-year event-free survival (+/-standard error) and overall survival (+/-standard error) were 68+/-8% and 76+/-7%, respectively. Excessive toxicities attributed to PEG-L-asparaginase and myelosuppression associated with cytosine arabinoside were encountered during consolidation resulting in early study closure and modification of therapy for those already enrolled. Ninety-two percent of methotrexate/cytosine arabinoside cycles were associated with grades 3 to 4 myelosuppression, and 24% resulted in delays in therapy of more than 7 days. Fifteen PEG-L-asparaginase related toxicities occurred in 13 patients (8 allergy, 4 pancreas, 2 central nervous system, and 1 hemorrhage). Intensification of therapy with PEG-L-asparaginase resulted in event-free survival and overall survival comparable to other studies of the same time period without the use of agents associated with long-term complications, such as anthracyclines, epipodophyllotoxins, and alkylating agents. However, excessive toxicity occurred with intensified PEG-L-asparaginase and antimetabolite based therapy delivered on this schedule.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Polietilenoglicóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Análise de Sobrevida , Falha de Tratamento , Resultado do TratamentoRESUMO
Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell count (WBC) less than 50 x 10(9)/L (50,000/microL), DNA findings of trisomies 4 and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS) leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients attained remission (3 induction deaths) and received 6 courses of intravenous methotrexate (1 g/m(2)) with daily mercaptopurine. Weekly intramuscular methotrexate was added during maintenance; pulses of vincristine and prednisone were administered with periodic intrathecal chemotherapy. Treatment duration was 2.5 years. No alkylators, epipodophylotoxins, anthracyclines, or radiation were given. The 6-year event-free survival (EFS) was 86.6% with overall survival (OS) of 97.2%. Patients with less than 5% marrow blasts on induction day 15 had superior EFS. A difference not reaching conventional statistical significance (P = .068) was noted for superior outcomes in patients with trisomies of chromosomes 4 and 10 versus those lacking double trisomies. Sex, ethnicity, CNS status, and WBC were not predictive. This indicates the great majority of children with lesser-risk B-lineage ALL are curable without agents with substantial late effects.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/administração & dosagem , Linhagem da Célula , Neoplasias do Sistema Nervoso Central/prevenção & controle , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Infusões Intravenosas , Injeções Intramusculares , Injeções Espinhais , Masculino , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevenção & controle , Prednisona/administração & dosagem , Indução de Remissão , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
PURPOSE: Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs). PATIENTS AND METHODS: Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation. The number of chemotherapy cycles was determined by rapidity of the initial response. Patients were assigned randomly to receive DRZ (n = 239) or no DRZ (n = 239) concomitantly with chemotherapy to evaluate its potential to decrease adverse cardiopulmonary outcomes. RESULTS: Ten patients developed SMN. Six of eight patients developed AML/MDS, and both solid tumors (osteosarcoma and papillary thyroid carcinoma) occurred in recipients of DRZ. Eight patients with SMN were first events. With median 58 months' follow-up, 4-year cumulative incidence rate (CIR) for AML/MDS was 2.55% +/- 1.0% with DRZ versus 0.85% +/- 0.6% in the non-DRZ group (P = .160). For any SMN, the CIR for DRZ was 3.43% +/- 1.2% versus CIR for non-DRZ of 0.85% +/- 0.6% (P = .060). Among patients receiving DRZ, the standardized incidence rate (SIR) for AML/MDS was 613.6 compared with 202.4 for those not receiving DRZ (P = .0990). The SIR for all SMN was 41.86 with DRZ versus 10.08 without DRZ (P = .0231). CONCLUSION: DRZ is a topoisomerase II inhibitor with a mechanism distinct from etoposide and doxorubicin. Adding DRZ to ABVE and ABVE-PC may have increased the incidence of SMN and AML/MDS.