RESUMO
This corrects the article DOI: 10.1038/leu.2015.246.
RESUMO
In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Antineoplásicos/normas , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Medula Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Leucemia Mieloide/mortalidade , Masculino , Indução de Remissão/métodos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the following prospectively in poor-risk neuroblastoma (NBL) patients: (1) the feasibility and efficacy of in vivo purging of bone marrow; and (2) the outcome after autologous bone marrow transplantation (ABMT) when immunologically tumor-free, unpurged autografts were used. PATIENTS AND METHODS: Twenty-three children with poor-risk NBL were evaluated during induction chemotherapy by repeat bone marrow examinations, including aspirate, biopsy, and an immunofluorescence method using the anti-GD2 monoclonal antibody 3A7. Nineteen patients completed the program with surgery with or without local irradiation followed by ABMT. RESULTS: Autologous bone marrow grafts, both immunologically and cytologically clean, were obtained and used in 19 of 23 children. The overall 4-year disease-free survival of the 19 grafted children was 53%, with a toxic death rate of 16% and a posttransplant relapse rate of 37%. According to the in vivo purging efficacy of the 18 children with initial marrow disease, the following three groups were formed: patients with (1) perfect in vivo purging (n = 5); (2) eventually successful in vivo purging (n = 8); and (3) unsuccesful in vivo purging (n = 5). The 4-year DFS was 100%, 67%, and 0%, respectively (P < 0.001). The five patients with unsuccessful in vivo purging failed because of resistant/progressive bulky disease. CONCLUSION: In patients with poor-risk NBL, in vivo purging of bone marrow by conventional chemotherapy is feasible, can be monitored, and the purging efficacy during the first 3 months after diagnosis is a strong prognostic factor reflecting tumor responsiveness to therapy. Autografting with immunologically clean, unpurged marrows gives a DFS well comparable to previous studies using ex vivo purging.
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Exame de Medula Óssea , Purging da Medula Óssea/métodos , Transplante de Medula Óssea , Neuroblastoma/terapia , Condicionamento Pré-Transplante , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos , Estudos de Viabilidade , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Neuroblastoma/patologia , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
We examined the recovery of circulating monocytoid (Lin- CD11+ HLA-DR+) and plasmacytoid (Lin- CD123+ HLA-DR+) precursor (pre) dendritic cell (DC) subsets after allogeneic stem cell transplantation (SCT) in 39 children, using age-matched healthy children as controls. The frequencies of DCs in peripheral blood samples were determined by flow cytometry. The initial recovery of DC occurred simultaneously with myeloid engraftment. However, with time, DC subset values declined, being very low 40-50 days after SCT. Low monocytoid and plasmacytoid DC values were associated significantly with the development of severe acute graft-versus-host disease (aGVHD) (P=0.042 and 0.017, respectively). Plasmacytoid DC values were lower than in the age-matched controls for the entire follow-up period (range 102-2569 days), although, with time, values approached normal levels. Normal monocytoid DC numbers were observed within 300-400 days post SCT. The severity of chronic GVHD did not correlate with quantitative recovery of DC. We conclude that in pediatric SCT, initial recovery of DC production is concurrent with that of myelopoiesis, yet with time, DC subset values decline and low counts are associated with severe aGVHD. Monocytoid DC numbers approach normal levels within a year of SCT, but plasmacytoid DC counts recover very slowly.
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Células Dendríticas/citologia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Adolescente , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunofenotipagem , Lactente , Masculino , Prognóstico , Fatores de Tempo , Transplante HomólogoRESUMO
While sophisticated data on specific problems are available, very little is known about the overall quality of life of long-term survivors of malignancies in childhood. We used a previously validated 15-dimensional questionnaire to examine the perceived health-related quality of life of 168 survivors, currently aged 16-35 years, who had been treated for a malignancy at a single institution between 1961 and 1993. All had been off therapy for at least 1 year (median, 12 years). In statistical terms, the quality of life score of the survivors was significantly better than that of 129 normal controls [0.966 versus 0.941 (theoretical maximum 1), respectively; P < 0.001]; however, a difference of this magnitude is most likely not clinically significant. There were no associations between original diagnosis and present quality of life, but the numbers in each diagnostic group were small. The survivors reported significantly better levels of vitality, distress, depression, discomfort, elimination and sleeping dimensions than the controls. Although we are presently not able to identify all the contributing factors, we speculate that the high perceived quality of life of long-term survivors of childhood malignancies is at least in part a consequence of denial mechanisms which compensate or even overcompensate the objectively measurable late effects of childhood cancer.
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Nível de Saúde , Neoplasias/reabilitação , Qualidade de Vida , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Locomoção , Masculino , Transtornos Mentais/etiologia , Neoplasias/psicologia , Neoplasias/terapia , SobreviventesRESUMO
A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 to halt an outbreak of poliomyelitis. Immunocompromised persons and their household contacts were excluded from the oral poliovirus vaccine target group and given instead a dose of inactivated poliovirus vaccine. This gave us an opportunity to determine whether immunocompromised persons are protected from poliomyelitis during an outbreak and oral poliovirus campaign. Fourteen children, ages 3 to 17 years, with leukemia were given a booster dose of a novel high antigen content, trivalent inactivated poliovirus vaccine. All but two responded by an at least 4-fold increase in serum-neutralizing antibodies to at least one poliovirus serotype. These results indicate that children with acute lymphocytic leukemia in remission respond well to a booster dose of inactivated poliovirus vaccine. Antibody concentrations to the uncommon local epidemic strain of type 3 poliovirus remained, however, relatively low in most patients (median, 1:6) suggesting relatively impaired heterologous response to vaccination. Possible spread of live vaccine viruses to the inactivated poliovirus-vaccinated children and their close contacts was evaluated by examining weekly fecal specimens from 20 children and their 19 regular adult contacts for cytopathic viruses. No polioviruses were isolated from 224 specimens examined, indicating that this high risk population was well-protected from unintended exposure to live polioviruses.
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Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/farmacologia , Adolescente , Anticorpos Antivirais/biossíntese , Criança , Pré-Escolar , Surtos de Doenças/prevenção & controle , Feminino , Finlândia , Humanos , Tolerância Imunológica , Leucemia/imunologia , Masculino , Poliomielite/epidemiologia , Poliovirus/imunologia , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/farmacologia , Vacinas Atenuadas/farmacologiaRESUMO
After an outbreak of hepatitis B virus (HBV) infection in a unit of pediatric oncology, the clinical outcome and HBV markers were followed in 1 child with chronic and 10 children with acute HBV infection for 12 months. Four children had acute hepatitis with jaundice whereas 7 of the infections were subclinical. Ten children had antecedent malignancies and 1 had aplastic anemia. Four patients died of causes unrelated to the hepatitis after periods of 2, 4, 8 and 10 months. All 3 children who were not immunosuppressed at the time of contracting the HBV infection quickly turned negative for hepatitis B surface antigen (HBsAg), whereas only 2 of 8 patients who were immunosuppressed by chemotherapy eventually became HBsAg-negative. The latter 8 patients were also hepatitis B e antigen (HBeAg)-positive. Two of them quickly cleared HBeAg, but 6 remained HBeAg-positive throughout the follow-up. In 6 of 9 patients HBsAg was also detected in saliva. These results suggest that children who are receiving anticancer chemotherapy have an increased risk of remaining HBeAg-positive and secreting HBsAg and possibly HBV in their saliva, which makes them particularly infective.
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Hepatite B/complicações , Hepatite B/imunologia , Neoplasias/complicações , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Hepatite B/mortalidade , Antígenos da Hepatite B/análise , Humanos , Masculino , Análise de SobrevidaRESUMO
In a double blind study of 58 episodes of fever and profound neutropenia, children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or placebo, combined with identical antimicrobial therapy, i.e. imipenem, on admission. The criteria for discontinuation of therapy were identical. A difference was demonstrated both in the number of hospital days, totaling 252 days in the rhGM-CSF group and 354 in the placebo group, days receiving antibiotics (220 vs. 322), and in the resolution of neutropenia (4.5 days vs. 6.0 days; P < 0.05). The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 (12%) in the rhGM-CSF group as opposed to 15 of 30 (50%) in the placebo group (P = 0.01). rhGM-CSF was well-tolerated. We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia.
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Febre/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neutropenia/tratamento farmacológico , Adolescente , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Análise Custo-Benefício , Método Duplo-Cego , Feminino , Febre/etiologia , Humanos , Lactente , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Proteínas Recombinantes/uso terapêuticoRESUMO
Serologic responses to hepatitis B vaccine were investigated in 197 pediatric cancer patients. The patients, ages 1 to 21 years, comprised 66 with solid tumors, 101 with hematologic malignancies and 30 with various benign conditions. Of them 51 were receiving cytotoxic chemotherapy and 114 had not received chemotherapy for 0.2 to 11 years. Three doses of plasma-derived hepatitis B vaccine (20 micrograms) were given at 0, 1 and 6 months; and antibody concentrations to hepatitis B surface antigen were determined at 3, 6 and 8 months. The geometric mean antibody concentration after 3 vaccine doses was 1076 mIU/ml in cancer patients receiving chemotherapy and 18,833 mIU/ml in cancer patients not receiving chemotherapy. The protective titer of antibody (> or = 10 mIU/ml) was reached after 3 doses of vaccine by 67% of patients receiving chemotherapy and by 97% of those not receiving chemotherapy. The patients being treated for solid tumors had weaker responses than those being treated for hematologic malignancies: after 3 vaccine doses no response was observed in 6 of 11 patients with solid tumors compared with 3 of 25 of patients with hematologic malignancies. Children receiving anticancer chemotherapy have essentially weaker responses to hepatitis B vaccine than children not receiving chemotherapy or those with benign conditions. This reflects the profound immunosuppression during chemotherapy. The effect of more intensive immunization schedules should be investigated.
Assuntos
Vacinas contra Hepatite B/imunologia , Tolerância Imunológica , Neoplasias/imunologia , Vacinação , Adolescente , Adulto , Análise de Variância , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Hepatite B/imunologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Hospedeiro Imunocomprometido/imunologia , Masculino , Neoplasias/tratamento farmacológicoRESUMO
The use of volunteer, unrelated donors has substantially increased the number of potential donors for pediatric marrow transplantation during the past few years. We describe our single institution experience of short-term toxicity after pediatric marrow transplantation using sibling or unrelated donors. Fully matched (A, B and DR loci) donors were employed in 94% of the cases in both groups. Conditioning of similar intensity and uniform supportive care were employed in the two groups. Both primary non-engraftment and secondary graft failure were more common among recipients of unmanipulated URD grafts. Clinically significant (grades III-IV) acute GVHD and toxic mortality during the immediate post-transplant period were also higher in this group of patients. Pediatric marrow transplantation using volunteer, unrelated donors appears to be associated with an increased incidence of procedure-related toxic complications.
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Transplante de Medula Óssea , Rejeição de Enxerto , Adolescente , Transplante de Medula Óssea/imunologia , Criança , Pré-Escolar , Feminino , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Fatores de Tempo , Doadores de Tecidos , Transplante HomólogoRESUMO
High-dose thiotepa was given as a single agent at a total dose of 1125 mg/m2 with autologous bone marrow rescue to nine patients with recurrent/refractory/poor risk pediatric malignancies (primitive neuroepithelial tumor (PNET), two; neuroblastoma, one; Wilms' tumor, one; osteosarcoma, one; Ewing's sarcoma one, Hodgkin's disease one, high-grade glioma, two). The response rate in these heavily pretreated patients was 71% (five out of seven evaluable patients) including two complete responses (Wilms', glioma), three partial responses (osteosarcoma, Ewing's sarcoma, Hodgkin's disease), and two with stable disease (PNET, glioma). The median duration of response was 2.5 months. The extramedullary toxicity was acceptable with symptoms mainly of skin and gastrointestinal tract. The data indicate that high-dose thiotepa is effective in several types of recurrent pediatric solid tumors, and merits further evaluation in combination regimens.
Assuntos
Transplante de Medula Óssea , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia , Tiotepa/administração & dosagem , Adolescente , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Estudos de Avaliação como Assunto , Feminino , Sobrevivência de Enxerto , Humanos , Infecções/etiologia , Masculino , Pele/efeitos dos fármacos , Tiotepa/efeitos adversos , Transplante AutólogoRESUMO
Invasive fungal infections (IFI) with substantial mortality constitute an increasing problem among BMT patients. From 1986 to 1996 148 children underwent BMT, and are included in a retrospective analysis of the incidence, risk factors and outcome of IFI. By histopathology or culture-proven IFI (Candida, 10; Aspergillus, 8) was documented in 12/73 (16%) allogeneic and in 6/75 (8%) autologous BMT patients. Of these 18 patients, 15 subsequently died, and in 12 (66%) IFI was regarded as the main cause of death. In addition to the patients with documented IFI, 48 had suspected and 82 no fungal infection. Invasive candidal infections were more frequent in patients with semiquantitatively estimated abundant candidal colonization as compared with those with no colonization (18% vs 3%, P = 0.015). In the allogeneic group, 50% of those with severe (grades III-IV) aGVHD had IFI as opposed to 8% of those with no or mild aGVHD (P < 0.001). Regarding cGVHD, 57% of those with extensive cGVHD vs 5% of those with absent or limited cGVHD had IFI (P < 0.001). The dose of steroids was associated with IFI: 77% of those who received high-dose steroids (methylprednisolone 0.25-1 g/day for 5 days) vs 5% of those with conventional-dose (prednisone 2 mg/kg/day) had IFI (P < 0.001). Particularly for BMT patients at risk, new, quicker and better diagnostic tests and more effective anti-fungal agents, both for prophylaxis and treatment, are needed.
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Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Micoses/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Doença Aguda , Adolescente , Corticosteroides/efeitos adversos , Antifúngicos/uso terapêutico , Candidíase/epidemiologia , Candidíase/etiologia , Cateterismo Venoso Central/efeitos adversos , Causas de Morte , Criança , Pré-Escolar , Doença Crônica , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/complicações , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Incidência , Lactente , Masculino , Metilprednisolona/efeitos adversos , Micoses/diagnóstico , Micoses/epidemiologia , Neutropenia/complicações , Prednisona/efeitos adversos , Pré-Medicação , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Acute GVHD is an important clinical problem frequently encountered in relation to stem cell transplantation. In its initial treatment glucocorticoids remain the established drug of choice. In the face of the side-effects related to therapy with glucocorticoids other, possibly less toxic, options for the initial treatment of acute GVHD might be of use. We report the successful treatment of progressive cutaneous acute GVHD up to grade II in five pediatric recipients of unrelated marrow grafts.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/administração & dosagem , Metotrexato/administração & dosagem , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Transplante HomólogoRESUMO
Pubertal development and androgen production were evaluated 1-10 years after bone marrow transplantation (BMT) in 15 females aged 14-23 (mean 17) years. Before BMT, these patients had received combination chemotherapy for hematologic malignancy, and all had had a transplant program including total body irradiation (TBI). Of the nine patients who were pre-menarcheal at BMT, two had subsequently experienced spontaneous menarche at 11.5 and 13.3 years of age. Six were post-menarcheal, but became amenorrheic after BMT. Menstruation subsequently started spontaneously in one of them 6 years after BMT. At the time of the study, three patients were early to mid-pubertal and 12 late pubertal or post-pubertal. Twelve patients were receiving sex steroid substitution therapy. Serum concentrations of testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) were determined. Androgen levels of late pubertal and post-pubertal transplanted patients were compared with 19 post-menarcheal patients aged 14-21 (mean 17) years who had been treated for hematologic malignancy with conventional chemotherapy. Testosterone levels of 52 healthy post-menarcheal females aged 14-29 (mean 19) years were measured as controls. Androgen levels of the BMT patients were lower than those of the conventionally treated patients. Differences in testosterone, androstenedione and DHEA levels were significant. Three spontaneously menstruating BMT patients had normal androgen levels. Testosterone levels of the conventionally treated patients and healthy controls were similar. Subnormal androgen production might be one factor behind the problems in pubertal development and sex life experienced by females after BMT. The use of these hormone levels for follow-up purposes and the potential value of androgen replacement therapy in females after TBI merit further study.
Assuntos
Androgênios/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/efeitos adversos , Feminino , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/fisiopatologia , Humanos , Puberdade/sangue , Fatores de Tempo , Irradiação Corporal TotalRESUMO
Gradual allograft rejection after initial good engraftment may occur with simultaneous autologous reconstitution particularly in patients receiving nonmyeloablative conditioning. Careful post-transplant follow-up of the chimerism status can reveal these cases early on, when the immunological balance may still be shifted to the donor cells. We describe two children with nonmalignant diseases, in whom imminent rejection of their sibling allografts was prevented with donor lymphocyte transfusions (DLT). DLT dosing and timing need to be individually guided by monitoring of the chimerism status.
Assuntos
Rejeição de Enxerto/prevenção & controle , Transfusão de Linfócitos , Criança , Pré-Escolar , Rejeição de Enxerto/diagnóstico , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Sistema Imunitário/fisiologia , Masculino , Regeneração , Quimeras de Transplante , Transplante HomólogoRESUMO
Eleven patients between the ages of 6 and 18 years who had been treated for acute leukemia were investigated for growth and growth hormone (GH) secretion. All had undergone bone marrow transplantation (BMT) between 0.7 and 5.1 (median 2.0) years previously. Preparation of patients for BMT had included high-dose cyclophosphamide and total body irradiation. In the eight patients at risk of growth failure, the relative height decreased 0.5-2.5 SD units (median 1.0) during the follow-up period. Eight patients secreted subnormal amounts of GH as studied by measuring spontaneous pulsatile GH secretion overnight. The maximal nocturnal GH peak varied between 3.3 and 28.3 micrograms/l (median 9.3). The mean nocturnal GH concentration varied from 1.2 to 8.3 micrograms/l (median 2.3) and depended on the length of the follow-up period. We conclude that deficient GH secretion is one reason for poor growth after BMT. A good growth response to GH substitution would support the role of GH deficiency in the observed growth retardation after BMT.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/deficiência , Adolescente , Criança , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Leucemia Mieloide Aguda/radioterapia , Leucemia Mieloide Aguda/cirurgia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgiaRESUMO
A retrospective, case-matched analysis of the short-term toxicity, risk of GVHD and relapse as well as outcome in pediatric unrelated marrow transplantation was conducted by comparing recipients of T-replete and -depleted grafts in a two-center setting. Both groups contained 30 patients with acute leukemia matched by age at transplant, gender, primary diagnosis and disease status. Acute (90% vs 53%) and chronic (48% vs 0%) GVHD were more common among recipients of T-replete grafts. No significant differences in graft rejection/failure or viral infections were encountered between the two groups. Relapses were more prevalent (37% vs 15%) among recipients of T-depleted grafts. Outcome (EFS) was similar in the two groups. Consequently, in the analysis of transplant outcome, the higher risk of procedure-related, toxic complications among pediatric recipients of T-replete marrow grafts appears to be balanced by an increased risk of relapse among the recipients of T-depleted grafts.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Doença Aguda , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Teste de Histocompatibilidade , Humanos , Lactente , Leucemia/imunologia , Depleção Linfocítica , Masculino , Estudos Retrospectivos , Imunologia de Transplantes , Transplante Homólogo , Resultado do TratamentoRESUMO
Chemo- and radiotherapy may have injurious effects on developing teeth. In this long-term follow-up study among poor-risk neuroblastoma (NBL) survivors our aims were: (1) to assess both the type and extent of the side-effects of the anticancer treatment on tooth development; and (2) to develop an index for expressing total damage to the permanent dentition. We studied the dental development from panoramic radiographs (PRG) of 18 long-term survivors treated under the age of 6 years with high-dose (HD) chemotherapy and autologous stem cell transplantation (ASCT) for poor-risk NBL. The myeloablative therapy was either HD chemotherapy and fractionated total body irradiation (TBI) of 10-12 Gy (TBI group, n = 10) or HD chemotherapy only (non-TBI group, n = 8). A defect index (DeI) was developed to describe the damage to the permanent dentition. The DeI was also tested in 18 healthy adolescents. All NBL patients had disturbances in dental development including short roots, arrested root development, microdontia and tooth aplasia. After TBI, 9/10 patients had very severe root defects, in contrast to none in the non-TBI group. All children in the TBI group had 2-12 (mean 6.6) missing permanent teeth, while 2/5 in the non-TBI group (3/8 excluded due to young age) had two and four missing permanent teeth, respectively. Microdontia was found at equal frequency in both groups. The mean value of the DeI was 70.0 (range 28-117) in the TBI group, 15.2 (range 4-34) in the non-TBI group (P<0.001, Mann-Whitney U test) and 1.8 (range 0-15) in healthy adolescents. Disturbances in dental development may compromise occlusal function in poor-risk NBL patients after ASCT, especially when TBI is included in the conditioning regimen. Long-term dental follow-up and rehabilitation is required.
Assuntos
Antineoplásicos/efeitos adversos , Dentição , Neuroblastoma/terapia , Transplante de Células-Tronco/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neuroblastoma/complicações , Odontogênese/efeitos dos fármacos , Odontogênese/efeitos da radiação , Anormalidades Dentárias/etiologia , Transplante AutólogoRESUMO
Ovarian function and sex hormone production with special focus on androgens (testosterone, androstenedione, dehydroepiandrosterone and its sulfate, DHEAS) was followed up during 1.5-20 (mean 9) years after bone marrow transplantation (BMT) in 24 female subjects aged 16-33 (mean 21) years at the last follow-up. All patients had received TBI and high-dose chemotherapy as the preparative regimen. A total of 24 female patients with conventionally treated pediatric hematologic malignancies served as controls. Four of 24 transplanted patients had spontaneous menstruation several years post transplantation, but in only one of them were serum FSH levels normal. Androgen levels of the BMT patients were lower than those of the conventionally treated patients. Subnormal testosterone levels were observed in 43% of BMT patients and subnormal DHEAS levels in 34% of BMT patients, the latter being a constant finding during glucocorticoid therapy for chronic GVHD (cGVHD). These results indicate that ovarian damage is a common late effect in patients transplanted at a young age, still having a seemingly normal pubertal development. Ovarian damage and cGVHD with glucocorticoid therapy are strongly associated with subnormal androgen levels. The clinical consequences of these changes and possible benefits of putative androgen replacement therapy remain to be elucidated.
Assuntos
Androgênios/sangue , Transplante de Medula Óssea/efeitos adversos , Glucocorticoides/administração & dosagem , Doença Enxerto-Hospedeiro/sangue , Doenças Ovarianas/sangue , Doenças Ovarianas/etiologia , Adolescente , Adulto , Androstenodiona/sangue , Criança , Pré-Escolar , Doença Crônica , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Estrogênios/administração & dosagem , Estrogênios/sangue , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Estudos Longitudinais , Menstruação , Testes de Função Ovariana , Puberdade , Testosterona/sangueRESUMO
Impaired growth after TBI prior to BMT has been a constant finding in children with leukemia. The growth of poor-risk neuroblastoma (NBL) survivors treated with myeloablative preparative regimens and ABMT at the Hospital for Children and Adolescents, University of Helsinki, since 1982 is reported. Two separate groups were analyzed: (1) The TBI- patients (n = 15) were conditioned with high-dose chemotherapy only. They had been treated at the age of 1.0-6.3 (mean 3.0) years and the post-ABMT follow-up time was 1.5-14.5 (mean 7.7) years. (2) The TBI+ patients (n = 16) had received TBI in addition to high-dose chemotherapy. They had been treated at the age of 1.3-4. 8 (mean 3.0) years, and the post-ABMT follow-up time was 1.5-8.0 (mean 4.7) years. The height standard deviation score (SDS) was similar for the two groups at the time of diagnosis, -0.3 +/- 1.2 (mean +/- s.d.), and at the time of ABMT, -0.7 +/- 1.1. After transplantation, the height SDS continued to decrease in the TBI+ group, the mean being -2.0 SDS at 5 years after ABMT. In the TBI-group, the mean height SDS remained within -0.7 to -0.9 to the 10 years of follow-up. Five patients received growth hormone (GH) therapy starting 2-6 years after ABMT. They all had low GH secretion in provocative tests. All showed some response to GH therapy. The mean height SDS increased 0.4 SDS during the 3 years following the start of GH therapy, while in the untreated patients a decrease of 0. 8 SDS during the corresponding time (P = 0.009) was observed. We conclude that NBL patients grow poorly following ABMT when TBI is included in the conditioning regimen, but close to normally when treated without TBI. The need for GH therapy should be evaluated early to avoid an unnecessary decrease in final height.