Cláudio Galvão de Castro

Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy

This study assessed the use of low‐energy laser in the prevention or reduction of the severity of oral mucositis.

Clinical features in osteosarcoma and prognostic implications

OBJECTIVE To identify the clinical features in osteosarcoma and to investigate their influence on the prognosis of children and adolescents presenting this disease. MATERIAL AND METHODS The records of children and adolescents with osteosarcoma treated by the Bone Tumors Group of the state of Rio Grande do Sul, Brazil, between January 1992 and December 2001 were reviewed. RESULTS Fifty consecutive patients were included in this study. Mean age at diagnosis was 13 years (3-22); 68% of the patients were males. The primary site of disease was the femur in 50% of the patients, tibia in 30%, pelvis in 4%, humerus in 10%, fibula in 2% and other sites in 4%. Nineteen patients presented metastases at diagnosis (38%). All patients received chemotherapy and were treated with three different schemes. As for surgical treatment, 26 patients (52%) had an amputation and 17 (34%) received conservative surgery. Serum lactic dehydrogenase > 1,000 UI/ml (p = 0.0159, log rank), tumor necrosis < 90% and presence of metastases had a negative influence on prognosis. The overall 5-year survival was of 33.2+/-7.2% with mean follow-up of 36 months (6-126). Event-free survival was 29.7+/-7%. The 5-year event-free survival in non-metastatic patients was 45+/-10.7%, and zero in metastatic patients (follow-up of 78.4 and 18.7 months, respectively). Only two out of 19 metastatic patients are alive and free of disease at 18 and 30 months respectively. CONCLUSION Metastatic disease at diagnosis, serum levels of serum lactic dehydrogenase > 1,000 UI/ml and tumor necrosis < 90% are predictors of unfavorable prognosis. The excessively high incidence of metastatic patients may suggest the presence of an aggressive pattern of disease in our population, or may indicate late diagnosis.

Oral health and dental anomalies in patients treated for leukemia in childhood and adolescence

This study was conducted to evaluate oral health and dental anomalies in children treated for acute lymphoblastic leukemia (ALL) and to compare results with those of a group of healthy children matched for sex and age.

X-linked adrenoleukodystrophy: clinical course and minimal incidence in South Brazil.

UNLABELLED X-linked adenoleukodystrophy is a genetic disease that affects the degradation of very long-chain fatty acids. In male patients, common pictures are the cerebral form (CALD), myeloneuropathy (AMN), and Addison-only. OBJECTIVE To describe the clinical course of affected male patients from South Brazil between 1993 and 2007. METHODS Affected male patients and their maternal lineages were studied from a clinical, neurological and biochemical standpoint. RESULTS Eighty-three male patients from 30 families were biochemically evaluated: 51 were affected. 27/51 (54%) presented the cerebral form; 11/51 had AMN (22%); 5 had Addison-only (10%), and 8 (16%) were asymptomatic. Between 2002 and 2006, the minimal incidence was 1:35,000 males in our State (South Brazil). Forty-three affected individuals were followed for 5.4+/-3.7 years. Of 10 boys detected at early stages, three developed CALD. These three boys and another five CALD at baseline were referred to hematopoietic stem cell transplantation. Seven transplants were carried out, 5 with good clinical evolution after 2.2 years post-transplant. The non-transplanted case was later defined as a stable cerebral form. DISCUSSION Among the present families, the observed cases were comparable to the 50% expected by Mendelian segregation. Based on the natural history, the number of cases that developed CALD was similar to the expected. Transplants were successful in 70% of cases. The occurrence of a stable cerebral form pointed to an urgent need for better markers of active cerebral disease.

High-dose chemotherapy and autologous peripheral blood stem cell rescue in a patient with pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor of the lung. Approximately 80 cases of PPB have been published, and in only three cases high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) was applied. A 5-year-old girl presenting with cough, fever, and shortness of breath was referred to the authors in March 1999. A computed tomography scan of the chest showed a tumor mass in the left hemithorax. The lesion was biopsied and the histopathologic report suggested the diagnosis of PPB. The patient received chemotherapy comprising vincristine, actinomycin D, and cyclophosphamide with only a minor response, and treatment was switched to ifosfamide, carboplatin, and etoposide, which produced a partial response. Tumor resection was performed, but margins were positive for PPB. Due to the high risk of recurrence, the authors elected to administrate high-dose chemotherapy using melphalan, etoposide, and carboplatin, followed by autologous HSCT. The patient achieved complete hematologic recovery, and reimaging after HSCT showed no evidence of disease. She relapsed 4 months later and died about 9 months after the completion of high-dose therapy. The role of high-dose chemotherapy and autologous HSCT is likely to be limited in PPB.

Safety of general anesthesia for lumbar puncture and bone marrow aspirate/biopsy in pediatric oncology patients.

Introduction Painful short duration procedures such as bone marrow aspiration/biopsy and the lumbar puncture with or without intrathecal chemotherapy are frequently performed during the treatment of children with cancer. This study evaluated the frequency and severity of complications of bone marrow aspiration biopsy and lumbar puncture/intrathecal chemotherapy under general anesthesia. Patients and Methods A prospective observational study was performed from November 2003 to August 2005. Patients with cancer younger than 21 years old, receiving treatment at the Pediatric Oncology Unity of Hospital de Clínicas de Porto Alegre, undergoing diagnostic and/or therapeutic short duration procedures carried out under general anesthesia in the outpatient surgery unit. Results One hundred and thirty-seven patients were submitted to 423 procedures under general anesthesia. There were 61% boys, mean age of 7.5 years (0.2 to 21) and ASA II 98%. Eighty seven percent of the procedures were carried out in patients with leukemia or lymphoma. The majority of the procedures had no adverse events during intraoperative and postoperative periods. No procedure had to be suspended after it had begun. One patient had lumbar pain after the procedure and was admitted to the ward with suspected subdural bleeding, but this was not confirmed. No patient needed cardiopulmonary reanimation or treatment in the intensive care unit. Conclusions General anesthesia for short duration painful procedures in children undergoing treatment for malignancies is safe when carried out by trained professionals in outpatient clinical surgery unit.

Estudo retrospectivo do tratamento de leucemia mielóide aguda com o transplante de medula óssea: a experiência brasileira

Data from the International Bone Marrow Transplant Registry (IBMTR) contribute for the improvement of Bone Marrow Transplant (BMT) worldwide. We studied the Brazilian experience in BMT for AML to compare this with international data. We performed a retrospective study by sending questionnaires to 16 BMT centers regarding clinical and treatment variables. Statistical analyses concerning autologous BMT (autoBMT) and allogeneic BMT (alloBMT) were performed using the Kaplan-Meier method and the log-rank test. All p-values were two-tailed. We collected data from 731 patients (205 autoBMT and 526 alloBMT). Median overall survival (OS) for autoBMT patients was longer than alloBMT patients (1035 vs. 466 days, p=0.0012). AlloBMT stem cell source (SCS): 73% bone marrow stem cell (BMSC), 23% peripheral blood stem cells (PBSC) and 4% umbilical cord blood. Among the autoBMT patients, the SCS was 63% PBSC, 22% BMSC and 15% both. The SCS did not impact on OS. There was no difference in OS between different FAB classifications in the alloBMT group, but in the autoBMT the M3 patients had longer survival. As expected, the main cause of mortality among autoBMT patients was related to disease relapse (60%), while in the alloBMT, to infection (38%). In both groups we found longer OS in first complete remission (1CR) compared to second (2CR) and other (p<0.0001), and longer OS in de novo AML than in secondary. In the alloBMT group we found more patients with advanced disease (60%), while in the autoBMT group, we found more M3 patients (24%), which could explain the difference in OS. Most of our results are in accordance with IBMTR data. One should consider the fact that this is a retrospective study and our findings should be analysed with caution.

Dasatinib after allogeneic stem cell transplantation in a child with Philadelphia chromosome positive acute lymphoblastic leukemia.

To the Editor: We read with interest the article ‘‘Successful second allogeneic stem cell transplantation in second remission induced by dasatinib in a child with Philadelphia chromosome positive acute lymphoblastic leukemia’’ [1]. We would like to share a similar experience with a 4-year-old male diagnosed with Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL) at our institution. He initially received conventional chemotherapy using an induction protocol similar to BFM 95 achieving a hematological remission, although he remained Ph PCR positive. Seven months after diagnosis he received bone marrow transplantation (BMT) from his identical matched HLA sister. Conditioning regimen consisted of etoposide 60 mg/kg and total body irradiation of 1,200 cGy. Conventional immunosuppressive doses of cyclosporine and methotrexate were used. He had no severe complications and no evidence of graft versus host disease. A bone marrow aspiration 2 months after BMT showed a complete remission and a female karyotype with no evidence of Ph chromosome. Three months post-BMT he had a bone marrow relapse; cyclosporin was resumed and he received induction chemotherapy with vincristine, asparaginase, and prednisone which lead to a bone marrow remission. Four months post-BMT he had a second relapse; following 1 month of re-induction therapy with oral etoposide, vincristine, prednisone, and asparaginase he again achieved a remission. IRB approved compassionate treatment with dasatinib was instituted 2 months later at the dose of 60 mg/m bid (40 mg bid) combined with vincristine (1.5 mg/m weekly for 4 weeks). Unfortunately after 2 months of therapy he had another relapse; prednisone and asparaginase were added to the schema and dasatinib was kept at the same dose. Bone marrow remission was again achieved; however, PCR for Ph was still positive. Due to his excellent clinical condition, he received a new transplantation from the same donor, using a non-myeloablative regimen with fludarabine, melphalan, and carmustine. Dasatinib was tapered off during conditioning and resumed 20 days after transplantation. Two months after the second BMT he had a CSF and the fourth bone marrow relapse. Dasatinib was tapered off and he received palliative care, dying 4 months after the second transplantation. In this heavily pretreated patient, dasatinib in combination with other agents was well tolerated with no moderate or severe toxicities; which is in concordance to the experience described by Milott et al. [1]. Unfortunately, we were not able to obtain a longterm remission of this disease. We believe that dasatinib deserves more investigational studies in children. CML and Ph positive ALL are rare in this population and prospective studies take a long time to be completed; we believe that sharing single cases or series of cases experiences may help children in this same condition.

Indicações de transplante de células-tronco hematopoéticas em pediatria: consenso apresentado no I Encontro de Diretrizes Brasileiras em Transplante de Células-Tronco Hematopoéticas - Sociedade Brasileira de Transplante de Medula Óssea, Rio de Janeiro, 2009

A Sociedade Brasileira de Transplante de Medula (SBTMO) promoveu o I Encontro de Diretrizes do Transplante de Medula Ossea em 2009. Para revisao das indicacoes de transplante em Pediatria baseadas em evidencias foi constituido grupo de trabalho com oncologistas e hematologistas com experiencia em pediatria. Os artigos cientificos foram cuidadosamente avaliados e, para cada doenca, foram definidas as evidencias para recomendacao dos transplantes (de A a C) e a qualidade destas evidencias (de 1 a 3). As recomendacoes incluem doencas hematologicas malignas e nao malignas, tumores solidos, imunodeficiencias e doencas de deposito tratadas com transplantes de celulas-tronco hematopoeticas, quer autologos, alogenicos de irmao HLA compativel ou nao aparentados (doadores adultos ou sangue de cordao umbilical). Como nao existem recomendacoes uniformemente aceitas em pediatria, nao foram incluidas recomendacoes para transplantes de intensidade reduzida, com manipulacao do enxerto e nem parcialmente compativeis. E importante ressaltar que todas as indicacoes sao baseadas no conhecimento atual e podem modificar-se com o tempo. Assim, esta revisao nao deve ser utilizada para aplicacao direta no cuidado do paciente sem levar em conta caracteristicas da doenca, do doador e fatores de risco do proprio paciente. Este trabalho nao deve ainda ser utilizado como documento que limite o acesso do paciente ao transplante adequadamente indicado. Ressaltamos ainda, nesta revisao, diferencas entre transplantes em criancas e em adultos, com algumas recomendacoes especificas para os transplantes em pediatria.

Paradoxes of hematology: When the old disappears and the new does not arrive

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), Comitê de Mieloma Múltiplo, Brazil International Myeloma Foundation-Latin America (IMF), Brazil Sociedade Brasileira de Transplante de Medula Óssea (SBTMO), Brazil Latin American Bone Marrow Transplant Association (LABMT), Brazil Sociedade Brasileira de Oncologia Pediátrica (SOBOPE), Brazil Santa Casa de Porto Alegre, Unidade de Hematologia/Oncologia Pediátrica, Porto Alegre, RS, Brazil Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), Brazil Sociedade Brasileira de Oncologia Clínica (SBOC), Brazil Universidade de São Paulo (USP), Faculdade de Medicina, São Paulo, SP, Brazil Hospital Israelita Albert Einstein, Programa de Hematologia e Transplante de Medula Óssea, São Paulo, SP, Brazil Associação Brasileira de Linfoma e Leucemia (ABRALE), Brazil