RESUMO
BACKGROUND: Childhood cancer survivors (CCSs) entering adulthood experience different problems, including late therapy-related complications. Long-term follow up (LTFU) is important for early intervention and psychosocial support for CCSs with late complications but it is frequently discontinued. This study aimed (i) to identify clearly the factors responsible for LTFU discontinuation, and (ii) to define the support needs of CCSs. METHODS: From July, 2017 to March, 2019 we conducted a questionnaire survey of 121 CCSs aged ≥ 18 years at the time of the survey to investigate people who have experienced childhood cancer and identify their support needs. This was conducted in cooperation with patient associations throughout Japan. The LTFU levels were determined by CCSs themselves based on their treatment history. Long-term follow-up rates and LTFU discontinuation factors were assessed using the Kaplan-Meier method and the Cox proportional-hazards model. RESULTS: Late complications were the most common problem encountered by CCSs (80%). The most common support need was "explanation of late complications by a physician," reported by 86.9% of respondents. The rate of LTFU continuation decreased over time. The LTFU was discontinued both for physicians' reasons (35.6%) and patients' reasons (64.4%). Not knowing the extent or level of one's LTFU was reported to be an independent factor (P < 0.05) preventing LTFU continuation. As necessary support to continue LTFU, 67.9% of respondents stated the need for "explanation of LTFU by a doctor" and 60.7% stated "convenience of outpatient visit". CONCLUSIONS: Childhood cancer survivors require support, especially for late complications. It is necessary to continue LTFU, raising LTFU awareness among physicians and CCSs.
Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Adulto , Criança , Neoplasias/complicações , Neoplasias/terapia , Sobreviventes/psicologia , Inquéritos e Questionários , Japão/epidemiologiaRESUMO
Congenital leukemia is a rare subgroup of childhood leukemia. Lineage switches in leukemic cells are relatively rare events, which have been occasionally reported in congenital leukemia. To the best of our knowledge, the survival of congenital leukemia patients with lineage switch has not been previously documented. This lack of documentation may be attributable to extremely poor prognosis of these patients. We describe a case of a newborn female with initial diagnosis of MLL-AF4 positive B-precursor acute lymphoblastic leukemia, who developed lineage switch to acute monocytic leukemia following the induction therapy. Although morphological remission was temporary, she received an HLA-haploidentical bone marrow transplant from her father with non-remission status because of an early relapse at the age of 4 months. Despite many difficulties such as graft-versus-host disease, growth impairment, and psychomotor retardation, she remained in remission for 3 years and 7 months after the transplant. This successful outcome suggests that the graft-versus-leukemia effect was potentially accomplished in the patient. Taken together, early HLA-haploidentical stem cell transplant following remission is required for congenital leukemia patients with lineage switch, and it may be an effective alternative for refractory patients.
Assuntos
Antígenos HLA/imunologia , Leucemia Monocítica Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Transplante de Células-Tronco , Feminino , Haplótipos , Humanos , Quimioterapia de Indução , Recém-Nascido , Leucemia Monocítica Aguda/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/congênito , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Recidiva , Indução de Remissão , Fatores de TempoRESUMO
PURPOSE: In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the "delayed local treatment (DL)" policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL. PATIENTS: From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed. RESULTS: Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, (123)I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation. CONCLUSIONS: Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Indução/métodos , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/tratamento farmacológico , 3-Iodobenzilguanidina , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Japão , Masculino , Neuroblastoma/cirurgia , Cintilografia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Cirurgia de Second-Look/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable approach for myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN); however, the event-free survival rate of patients with pediatric MDS and MPN is still only approximately 60%. Although salvage HSCT is the only curative approach for patients with the failure of previous HSCT, its safety and efficacy have yet to be determined. PROCEDURES: We retrospectively analyzed 51 pediatric MDS or MPN who received salvage HSCT for relapse or graft failure following HSCT using registry data of the Japan Society for Hematopoietic Cell Transplantation. The indications used for salvage HSCT were relapse in 22 patients and graft failure in 29 patients. RESULTS: The overall survival (OS) rate for salvage HSCT in relapsed patients was 49.0 ± 10.8% at 3 years. The cumulative incidence of relapse following salvage HSCT was 29.8 ± 10.7% at 3 years, whereas the incidence of non-relapse mortality (NRM) was 28.6 ± 10.2%. No significant differences were observed in the OS after salvage HSCT between disease types. Twenty-four of 29 patients who received salvage HSCT for graft failure achieved engraftment, resulting in an engraftment probability of 81.5 ± 8.0% on day 100. The OS rate after salvage HSCT for graft failure was 56.8 ± 9.6% at 3 years. CONCLUSIONS: Second HSCT should be considered as a valuable option for the patients with relapse and graft failure in patients with pediatric MDS or MPN after HSCT, but high NRM is an important issue that needs to be addressed.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transtornos Mieloproliferativos/cirurgia , Terapia de Salvação/métodos , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Transtornos Mieloproliferativos/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Terapia de Salvação/mortalidade , Transplante HomólogoRESUMO
Immediate allergy to l-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific immunoglobulin G (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to be useful in diagnosing IgE-mediated allergies. We compared the diagnostic utility of the CD203c-BAT to that of ASP-IgG levels in determining ASP allergies in children. Eight ASP allergic reactions occurred over 75 ASP treatment courses. The sensitivity, specificity and area under the receiver operating characteristic curve of CD203c-BAT were similar to the ASP-IgG levels (0.75 vs. 0.85, 0.82 vs. 0.78 and 0.81 vs. 0.85, respectively). Positive skin prick test results in patients with ASP allergy suggested that ASP-IgE was one of the key players in ASP allergy. A combination of the BAT with the ASP-IgG level had the highest specificity (0.95) and positive predictive value (0.62), which permitted us to identify ASP allergy more effectively.
Assuntos
Asparaginase/imunologia , Basófilos/imunologia , Basófilos/metabolismo , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/metabolismo , Adolescente , Biomarcadores/sangue , Biomarcadores/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Linfoma/complicações , Linfoma/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sensibilidade e EspecificidadeRESUMO
The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Doença Aguda , Adolescente , Asparaginase/administração & dosagem , Criança , Pré-Escolar , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Soft tissue sarcomas (STS) of pelvic origin in boys often involve the urogenital organs. The optimal extensiveness of radical surgery has long been an issue of discussion, since exenterative surgeries result in severe urogenital adverse effects. We conducted a retrospective review of patients with pelvic STS treated in two regional center hospitals and assessed the radicality of surgery and the functional outcome of the bladder. PATIENTS: Medical records and surgical reports of nine cases (embryonal rhabdomyosarcoma 6, malignant triton tumor 2, suspected rhabdomyosarcoma 1) treated within 1997-2012 were reviewed. Site of origin was prostate in seven, retroperitoneal in two. Average follow-up period was 96 months. TREATMENT AND OUTCOME: All cases were subjected to neoadjuvant chemotherapy. Response was PR in four, SD in two, and PD in two. Radical surgery resulted in gross total resection in eight, and partial resection in one. Three underwent cystoprostatectomy, two cases underwent prostatectomy, and bladder-preserving tumor resection was carried out in four cases. At the last follow-up, three retained a functional bladder. Two required augmentation cystoplasty with intestinal conduits. CONCLUSIONS: The majority of the on-going clinical trials recommend conservative surgery for bladder/prostate rhabdomyosarcoma, and to preserve the bladder function particularly in chemosensitive tumors. Some other groups, however, advocate the importance of radical surgery to prevent local relapse. These reports include heterogenous group of patients in the cohort, and therefore it is difficult to draw a conclusion of which approach truly contributes to the survival of the patients better. Future studies should evaluate bladder and sexual function objectively to establish reliable evidence regarding the benefit and adverse effects of different surgical approaches. These data would be informative to optimize the treatment balance for children with pelvic rhabdomyosarcomas.
Assuntos
Neoplasias Pélvicas/cirurgia , Rabdomiossarcoma/cirurgia , Sarcoma/cirurgia , Micção/fisiologia , Neoplasias Urogenitais/cirurgia , Procedimentos Cirúrgicos Urogenitais/métodos , Pré-Escolar , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/fisiopatologia , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/fisiopatologia , Sarcoma/diagnóstico , Sarcoma/fisiopatologia , Resultado do Tratamento , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/fisiopatologiaRESUMO
T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are combined into one category as T lymphoblastic leukaemia/lymphoma in the current World Health Organization (WHO) classification. However, there is still ongoing discussion on whether T-ALL and T-LBL are two separate entities or represent two variant phenotypes of the same disease. Cytogenetic analysis has been used to identify the molecular background of haematological malignancies. To compare the distribution of chromosomal abnormalities of T-ALL and T-LBL, large series of cytogenetic data are required, but are absent in T-LBL in contrast to the abundant data in T-ALL. Among 111 T-LBL cases in our clinical trial, we obtained complete cytogenetic data from 56 patients. The comparison between our cytogenetic findings and those from three published T-LBL studies revealed no significant difference. However, meta-analysis showed that translocations involving chromosome region 9q34 were significantly more common in T-LBL than in T-ALL. In particular, four out of the 92 T-LBL cases, but none of the 523 paediatric T-ALL cases, showed translocation t(9;17)(q34;q22-23) (P=0·0004). Further studies are needed for the possible linkage between abnormal expression of genes located at 9q34 and/or 17q22-23 and the unique 'lymphoma phenotype' of T-LBL.
Assuntos
Aberrações Cromossômicas , Linfoma de Células T/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Criança , Pré-Escolar , Humanos , LactenteRESUMO
OBJECTIVE: The authors report a case of mediastinal lymphangioma successfully treated with Kampo medicine. METHODS: A 2-year-old boy with an axillary soft mass consulted our clinic. Physical examination findings were normal except for axillary elastic swelling. The neck and chest magnetic resonance imaging scan (MRI) showed a multilocular mass starting from a cervical lesion and extending above the carina. RESULTS: After 9 months of Kampo administration, MRI showed marked regression of mediastinal lymphangioma. CONCLUSIONS: It was found that Kampo medicine might be safe and effective as an alternative choice of treatment for lymphangiomas.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Linfangioma/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Medicina Kampo/métodos , Terapia Nutricional , Fitoterapia , Pré-Escolar , Humanos , Linfangioma/patologia , Magnoliopsida , Masculino , Neoplasias do Mediastino/patologia , Mediastino/patologia , Minerais/uso terapêutico , Extratos Vegetais/uso terapêuticoRESUMO
The present study aimed to identify optimal treatment intensity in children with mosaic Down syndrome (DS) and acute megakaryoblastic leukemia (AMKL). A retrospective review of AMKL patients was undertaken to identify mosaic DS children. Between November 1992 and November 2007, seven children were diagnosed as mosaic DS and AMKL. The median age at diagnosis was 29 months (range 4-34 months). Three patients had a past history of transient abnormal myelopoiesis. UPN1-4 were treated with intermediate-dose cytarabine and UPN4 received additional one course of high-dose cytarabine. All of these patients were remained in first CR. UPN5-7 were treated with high-dose cytarabine according to the AML99 protocol. UPN5 with GATA1 mutation suffered from acute pneumonia and pancreatitis and discontinued chemotherapy. UPN7 relapsed after cessation of chemotherapy and was rescued with allo-PBSCT. The cumulative doses of cytarabine were 3.5-10.65 g/m(2) in the UPN1-4 and 40.4-78.4 g/m(2) in the UPN5-7. The 8-year overall survival was 100% and the 8-year event-free survival 85.7%, respectively. Our retrospective study reveals that patients with mosaic DS and AMKL have a good prognosis. Reduction in intensity may work in patients with mosaic DS as well as with AML-DS.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Síndrome de Down/genética , Síndrome de Down/mortalidade , Leucemia Megacarioblástica Aguda , Mosaicismo , Pré-Escolar , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Fator de Transcrição GATA1/genética , Humanos , Lactente , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/mortalidade , Masculino , Prevalência , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Since neither a standard treatment nor a protocol study for single-system single site (SS-s)-type Langerhans cell histiocytosis (LCH) exists, we conducted a nationwide survey in Japan to clarify the epidemiology and clinical outcome of this subtype. PROCEDURE: Questionnaires regarding the clinical course of children with SS-s-type LCH diagnosed between 1995 and 2006 were sent to all members of the Japanese Society of Pediatric Hematology. RESULTS: One hundred forty-six children with histologically proven SS-s LCH were evaluable. The most frequently affected organ was bone (82%), followed by skin (12%). Few patients (14%) had a CNS-RISK lesion defined by the Histiocyte Society. Patients with a skin lesion were diagnosed at a significantly younger age than patients with a bone lesion (median: 6 months vs. 5 years 11 months, P < 0.001). The treatment regimen varied, but one-third of the patients in total and 71% of patients with a CNS-RISK lesion received chemotherapy that did not include etoposide. All but one patient attained remission. Ten patients (7%) showed reactivation. Of these, all eight with an initial bone lesion only exhibited reactivation in the bone(s). One patient with an initial skin lesion exhibited reactivation in the thymus. None of the patients died from disease progression or treatment complications. CONCLUSIONS: Our retrospective study, in which a relatively large proportion of the patients received chemotherapy, reveals that patients with SS-s LCH have a good prognosis. A prospective study should be conducted to confirm this and to identify the most effective and least toxic therapy for SS-s LCH.
Assuntos
Histiocitose de Células de Langerhans/epidemiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID). STUDY DESIGN: Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3). RESULTS: TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10(4) to 10(5) copies/microg DNA. In contrast, TRECs were extremely low in all neonatal Guthrie cards (n = 15) and peripheral blood (n = 14) from patients with SCID, including those with maternal T-cell engraftment or leaky T cells with hypomorphic RAG1 mutations or LIG4 deficiency. There were no false-positive or negative results in this study. CONCLUSION: TRECs quantification can be used as a neonatal mass screening for patients with SCID.
Assuntos
Reparo do DNA/genética , Triagem Neonatal/métodos , Receptores de Antígenos de Linfócitos T/genética , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribonuclease P/sangue , Imunodeficiência Combinada Severa/sangue , Adulto JovemRESUMO
From June 1996 to January 2001, 91 patients with B-cell non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia up to 18 years of age were enrolled in Tokyo Children's Cancer Study Group (TCCSG) NHL B9604 protocol study. Five-day intensive chemotherapy courses including high-dose methotrexate and high-dose cyclophosphamide were used for localized disease (Groups A and B). High-dose cytarabine was added for advanced disease (Groups C and D). Fifteen patients experienced an adverse event. There were three induction failures, eight relapses (three local, four bone marrow (BM), one BM + local), two toxic deaths and two second malignant neoplasm. Event-free survival at 6 years in Group D and in all patients was 82.4% +/- 9.2% and 81.9% +/- 4.4%, respectively. The TCCSG NHL B9604 protocol achieved an excellent treatment outcome especially in patients with the most advanced disease (Group D: high BM blast cell burden and/or central nervous system involvement).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Linfoma de Burkitt/mortalidade , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Humanos , Lactente , Metotrexato/administração & dosagem , Segunda Neoplasia Primária , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) sometimes suffer from adverse long-term sequelae. We analyzed the incidence, clinical course and prognosis of moyamoya syndrome (MoS) following childhood ALL. PROCEDURE: A total of 1,846 ALL patients were treated with four consecutive TCCSG ALL protocols (L84-11, L89-12, L92-13, and L95-14) between 1984 and 1999. We surveyed the MoS cases among these patients in the follow-up studies. RESULTS: Six patients with MoS were identified: four boys and two girls whose ages ranged from 2 years and 1 month (abbreviated as "2y1m") to 14y 1 m at diagnosis of ALL. None of the patients had central nervous system (CNS) leukemia. All six patients received prophylactic cranial irradiation with a dosage of 18 or 24 Gy. Although one patient died of brain infarction due to MoS, no leukemic relapse was observed in the group. The cumulative incidence of MoS in our series was 0.46 +/- 0.02% at 8 years. Among several clinical characteristics, use of cranial irradiation was the only factor that appeared to be significantly related to the development of MoS. CONCLUSIONS: MoS occurs with increased frequency in children treated for ALL, and might be associated with cranial irradiation. Prophylactic cranial irradiation should be used cautiously in ALL patients who can be cured by other CNS-directed therapies.
Assuntos
Irradiação Craniana/efeitos adversos , Doença de Moyamoya/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/administração & dosagem , Infarto Cerebral/etiologia , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Suscetibilidade a Doenças , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Doença de Moyamoya/diagnóstico , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Prednisolona/administração & dosagem , Qualidade de Vida , Indução de Remissão , Vincristina/administração & dosagemAssuntos
Injúria Renal Aguda/etiologia , Síndrome de Down/complicações , Hipotensão/complicações , Transtornos Mieloproliferativos/complicações , Síndrome de Lise Tumoral/complicações , Síndrome de Down/patologia , Evolução Fatal , Feminino , Hematopoese Extramedular , Humanos , Recém-Nascido , Mielopoese , Transtornos Mieloproliferativos/congênito , Transtornos Mieloproliferativos/patologiaRESUMO
PURPOSE: To evaluate whether dexamethasone (DEXA) yields a better outcome than prednisolone (PRED) in a prospective, randomized, controlled trial for the treatment of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Two hundred thirty-one standard-risk (SR) patients and 128 intermediate-risk (IR) non-B-cell ALL patients were registered from March 1995 to March 1999. After random assignment in each group, the PRED arm patients received PRED 60 mg/m2 during induction followed by PRED 40 mg/m2 over four intensifications in the SR group and three intensifications in the IR group. DEXA arm patients received DEXA 8 mg/m2 during induction and DEXA 6 mg/m2 during the intensifications. The maintenance phase was continued until week 104. RESULTS: Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1% +/- 3.9% (n = 117) and 84.4% +/- 5.2% (n = 114), respectively, in the SR group (P = .217) and 84.9% +/- 4.6% (n = 62) and 80.4% +/- 5.1% (n = 66), respectively, in the IR group (P = .625). The primary reason for treatment failure was marrow relapse. Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm. Although complications were more prevalent in the DEXA arm than in the PRED arm, fatal toxicity was rare both groups. CONCLUSION: DEXA administered at 8 mg/m2 during induction and 6 mg/m2 during intensification showed no advantage over PRED administered at 60 mg/m2 during induction and 40 mg/m2 during intensification in both the SR and IR groups.
Assuntos
Dexametasona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisolona/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Japão , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Probabilidade , Estudos Prospectivos , Recidiva , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
A 4-year-old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein-Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV-associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen-positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma.
Assuntos
Herpesvirus Humano 4/isolamento & purificação , Mononucleose Infecciosa/patologia , Linfoma de Células B/patologia , Adenoidectomia , Pré-Escolar , DNA de Neoplasias/análise , Evolução Fatal , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Glucocorticoides/uso terapêutico , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Mononucleose Infecciosa/tratamento farmacológico , Mononucleose Infecciosa/metabolismo , Linfoma de Células B/complicações , Linfoma de Células B/genética , Reação em Cadeia da Polimerase , TonsilectomiaRESUMO
Long-term survivors of acquired aplastic anemia (AA) have an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after immunosuppressive therapy (IST). It is uncertain whether the increased survival time simply discloses the natural history of AA as a premalignant disease or whether secondary disease is related to the therapy itself. Between November 1992 and September 1997, 113 AA children with normal cytogenetics at diagnosis were treated with IST using antithymocyte globulin, cyclosporin, and danazol with or without granulocyte colony-stimulating factor (G-CSF). We assessed risk factors for developing MDS/AML by Cox proportional hazards models. Twelve of 113 patients developed MDS between 9 and 81 months following the time of diagnosis, giving a cumulative incidence of 13.7 +/- 3.9%. The following cytogenetic abnormalities were observed at the time of diagnosis of MDS: monosomy 7 (6 patients), monosomy7/trisomy21 (1 patient), trisomy 11 (1 patient), del (11) (9?:14) (1 patient), add (9q) (1 patient), add 7 (q 32) (1 patient), and trisomy 9 (1 patient). The number of days of G-CSF therapy and nonresponse to therapy at 6 months were statistically significant risk factors by multivariate analysis. The present study suggests a close relationship between long-term use of G-CSF and secondary MDS in nonresponders to IST.
Assuntos
Anemia Aplástica/patologia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Imunossupressores/efeitos adversos , Leucemia Mieloide/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Doença Aguda , Adolescente , Adulto , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/genética , Criança , Pré-Escolar , Cromossomos Humanos Par 7 , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Incidência , Lactente , Cariotipagem , Leucemia Mieloide/etiologia , Leucemia Mieloide/genética , Masculino , Monossomia , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/genética , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
We reported a 15-year-old boy with an acute myelomonocytic leukemia and FK 506-induced leukoencephalopathy. He was received FK 506 for graft versus host disease occurred after peripheral blood stem cell transplantation. He, four weeks later, had generalized seizures and consciousness disturbance. The serum level of FK 506 was high (27.5 ng/ml). His brain MRI showed abnormal high intensity areas in the frontal and parietal white matter lesions on T2-weighted images. Neuropathological studies revealed the destruction of myelin sheeths and axons in the cerebral white matter corresponded with abnormal lesions on MRI. There were calcification and mineralization in the small vessel walls of the cortex and white matter. Osteopontin immunoreactivity was detected in the endothelial cells of small vessels. These findings suggest that the vascular damage was involved in the FK 506-induced leukoencephalopathy.
Assuntos
Encefalopatias/induzido quimicamente , Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/efeitos adversos , Tacrolimo/efeitos adversos , Adolescente , Encefalopatias/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielomonocítica Aguda/terapia , Imageamento por Ressonância Magnética , MasculinoRESUMO
Interferon (IFN)-gamma-mediated immunity plays an important role in host defense against intracellular pathogens, especially mycobacteria. Six Japanese children with bacille Calmette-Guérin (BCG) osteomyelitis were evaluated (1 disseminated, 3 multiple, and 2 solitary types) for mutations of genes involved in interleukin-12-dependent, IFN-gamma-mediated immunity. Heterozygous small deletions with frameshift (818del4 and 811del4) that are consistent with the diagnosis of partial dominant IFN-gamma receptor 1 (IFN-gammaR1) deficiency were detected in 3 unrelated patients. Expression of IFN-gammaR1 on monocytes was significantly increased in all 3 patients. Screening of family members with recurrent and disseminated mycobacterial infections found the identical deletion in 1 of the fathers. Antimycobacterial treatment was effective in these patients and resulted in good clinical outcome. This study demonstrated that partial dominant IFN-gammaR1 deficiency was the most common in Japanese patients who showed predisposition to curable BCG osteomyelitis.