RESUMO
OBJECTIVES: Few studies have detected qualitative and quantitative aspects of patients who underwent HSCT during childhood. The aims of this study are to explore the most recurrent narrative themes of HSCT experience in families five years after the procedure, and to observe statistical correlations between meaning attributed to the experience and defined variables. METHODS: Thirty-five families of pediatric HSCT survivors participated in the research. Both survivors and their families were asked to write a brief composition about their disease experiences. Qualitative analysis of the texts was performed using the T-LAB software. Information about medical aspects and psychological problems in HSCT survivors were collected with interviews and administering the Child Behavior Checklist 6-18. RESULTS: HSCT survivor families that reported the presence of externalizing and internalizing symptoms focused on thematic areas concerning broken families with separation between parents and the affected child versus healthy children. CONCLUSIONS: Long term psychological problems seem to be connected to the perception of family disruption. Specifically, family relationships seem to be the factor that protects from or enhances the risk of psychopathology in HSCT survivors. Moreover, the use of metaphoric terms to refer to HSCT presents higher associations with psychopathology. On the contrary, the possibility of referring directly to the transplantation is associated with psychological well-being. It is important to consider the family as a group in order to improve care.
Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Sobreviventes/psicologia , Adolescente , Criança , Família/psicologia , Feminino , Humanos , Masculino , Narração , Pesquisa Qualitativa , Sobreviventes/estatística & dados numéricosRESUMO
BACKGROUND: Pediatric oncohematologic patients are a high-risk population for clinical deterioration that might require pediatric intensive care unit (PICU) admission. Several studies have described outcomes and mortality predictors for patients post hematopoietic stem cell transplantation (HSCT), but fewer data exist regarding the category of non-HSCT patients. PROCEDURE: All oncohematologic non-HSCT patients ≤18 years requiring PICU admission from 1998 to 2015 in our tertiary-care academic hospital were retrospectively evaluated by means of the pediatric hematology-oncology unit database and the Italian PICUs data network database. We assessed the relation between demographic and clinical characteristics and 90-day mortality after PICU admission. RESULTS: Of 3750 hospitalized oncohematologic patients, 3238 were non-HSCT and 63 (2%) of them were admitted to the PICU. Patients were mainly affected by hematological malignancies (70%) and mostly were in the induction-therapy phase. The main reasons for admission were respiratory failure (40%), sepsis (25%), and seizures (16%). The median PICU stay was 5 days (range 1-107). The mortality rate at PICU discharge was 30%, and at 90 days it was 35%. Fifty-five percent of deaths happened in the first 2 days of the PICU stay. Cardiac arrest (P = .007), presence of disseminated intravascular coagulation (DIC, P = .007), and acute kidney injury (AKI) at PICU admission (P < .001) and during PICU stay (P = .021) were significant predictors of mortality in the multivariate analysis. Respiratory failure and mechanical ventilation were not associated with mortality. CONCLUSIONS: A relatively small percentage of non-HSCT patients required PICU admission, but the mortality rate was still high. Hemodynamic instability, DIC, and AKI, but not respiratory failure, were significant predictors of mortality.
Assuntos
Neoplasias Hematológicas/mortalidade , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34+ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.
Assuntos
Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Humanos , Lactente , Itália , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêuticoRESUMO
To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT.
Assuntos
Cuidados Críticos , Transplante de Células-Tronco Hematopoéticas , Insuficiência de Múltiplos Órgãos , Admissão do Paciente , Insuficiência Respiratória , Choque Séptico , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Lactente , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/etiologia , Choque Séptico/mortalidade , Choque Séptico/terapia , Taxa de SobrevidaRESUMO
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration.
Assuntos
Osteopetrose/genética , Ligante RANK/genética , Animais , Consanguinidade , Feminino , Genes Recessivos , Humanos , Masculino , Camundongos , Osteoclastos , LinhagemRESUMO
Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Esteroides/uso terapêutico , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Doadores não RelacionadosRESUMO
Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long-term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long-term results of high-dose IM (340 mg/m2 /d) in CML patients in chronic phase (CP-CML) aged <18 years at diagnosis. A total of 47 CP-CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91.5% of the evaluable patients at a median time of 6 months. BCR-ABL1 International Scale ≤ 0.1% (major molecular response; MMR) and ≤0.01% (molecular response; MR) at 12 months were 66.6% and 33%, respectively. During follow-up, MMR and MR were achieved in 78.6% and 61% of children, respectively. IM was safely discontinued in 3 long-term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression-free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow-up of 52 months (range 3-146), all patients are alive. High-dose IM is a long-term effective therapy in children and adolescents with CP-CML.
Assuntos
Antineoplásicos/administração & dosagem , Benzamidas/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Itália , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Transplante de Células-Tronco , Taxa de SobrevidaRESUMO
BACKGROUND: After hematopoietic stem cell transplantation, invasive aspergillosis remains one of the most lethal infections. Susceptibility may be due to prophylaxis and treatment of graft-vs.-host disease in T-cell-replete transplants, and delayed immune rebuilding due to T-cell depletion in haploidentical transplantation. METHODS: We monitored CD4(+) T-cell recovery and anti-Aspergillus immune competence in pediatric recipients of T-cell-replete matched transplants and of prevalently adult recipients of T-cell-depleted matched or haploidentical transplants for hematological malignancies. RESULTS: Although CD4(+) T-cell counts were higher in T-cell-replete transplant recipients at all post-transplant time points, Aspergillus-specific T cells were first detected 15-18 months after T-cell-replete matched, 7-9 months after T-cell-depleted matched, and 9-12 months after haploidentical transplantation, respectively. Incidence of invasive aspergillosis was 22% with 10% mortality after T-cell-replete transplants, 0% after T-cell-depleted matched, and 7% with 4% mortality after haploidentical transplants. CONCLUSIONS: Although T-cell counts were significantly higher after T-cell-replete transplants, post-transplant immune suppression/GvHD appeared to impair their function. Specific Aspergillus immune competence recovered faster after T-cell-depleted transplants, whether matched or haploidentical. T-cell-replete transplants were associated with a higher incidence of invasive aspergillosis and Aspergillus-related deaths. These results showed that T-cell depletion without post-transplant immunosuppression is associated to a faster immune recovery than T-cell-replete transplantation.
Assuntos
Aspergilose/etiologia , Aspergillus/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Depleção Linfocítica , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Aspergilose/epidemiologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunidade Celular , Imunofenotipagem , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Linfócitos T/metabolismo , Adulto JovemRESUMO
We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children.
Assuntos
Coleta de Amostras Sanguíneas/efeitos adversos , Coleta de Amostras Sanguíneas/métodos , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adolescente , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Transplante de Células-Tronco de Sangue Periférico , Irmãos , Doadores de Tecidos/psicologiaRESUMO
BACKGROUND: CareNet is the IT-based tool for Case and Care Management (CCM) in Tyrol, which facilitates standardised documentation of CCM activities. OBJECTIVES: Analysing the pilot usage of CareNet Tyrol. METHODS: Evaluation of the success and user experience of CareNet, expert interviews and a questionnaire-based assessment. RESULTS: Feedback from users in both phases indicated that the CareNet platform provides general benefits, but falls short of fully supporting the daily work of CCM experts and avoiding the need for parallel use of different documentation tools. CONCLUSION: This paper provides an insight into the ongoing transition to digital documentation for CCM at LIV Tyrol. While user feedback highlights areas for improvement, digital documentation is proved to be beneficial for the CCM team.
Assuntos
Administração de Caso , Humanos , DocumentaçãoRESUMO
We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high.
Assuntos
Doenças Autoimunes/terapia , Transplante de Células-Tronco Hematopoéticas , Neutropenia/terapia , Trombocitopenia/terapia , Adolescente , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neutropenia/imunologia , Neutropenia/patologia , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Trombocitopenia/imunologia , Trombocitopenia/patologia , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Acute lymphoblastic leukemia (ALL) in second complete remission is one of the most common indications for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. We compared the outcome after HCST of adolescents, aged 14 to 18 years, with that of children (ie, patients < 14 years of age). Enrolled in the study were 395 patients given the allograft between January 1990 and December 2007; both children (334) and adolescents (61) were transplanted in the same pediatric institutions. All patients received a myeloablative regimen that included total body irradiation in the majority of them. The donor was an HLA-identical sibling for 199 patients and an unrelated volunteer in the remaining 196 patients. Children and adolescents had a comparable cumulative incidence of transplantation-related mortality, disease recurrence, and of both acute and chronic graft-versus-host disease. The 10-year probability of overall survival and event-free survival for the whole cohort of patients were 57% (95% confidence interval, 52%-62%) and 54% (95% confidence interval, 49%-59%), respectively, with no difference between children and adolescents. This study documents that adolescents with ALL in second complete remission given HSCT in pediatric centers have an outcome that does not differ from that of patients younger than 14 years of age.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Quimiorradioterapia/métodos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Transplante HomólogoRESUMO
To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Anticorpos Monoclonais Murinos/uso terapêutico , Doenças Autoimunes/etiologia , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Europa (Continente) , Feminino , Glucocorticoides/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lactente , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Rituximab , Resultado do Tratamento , Adulto JovemRESUMO
The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if ≥ 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD ≥ 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; "Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia," protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/classificação , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Humanos , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
Children with high-risk acute lymphoblastic leukemia in first complete remission can benefit from allogeneic hematopoietic stem cell transplantation. We analyzed the outcome of 211 children with high-risk acute lymphoblastic leukemia in first complete remission who were given an allogeneic transplant between 1990 and 2008; the outcome of patients who, despite having an indication for transplantation and a suitable donor, did not receive the allograft for different reasons in the same time period was not analyzed. Sixty-nine patients (33%) were transplanted between 1990 and 1999, 58 (27%) between 2000 and 2005, and 84 (40%) between 2005 and 2008. A matched family donor was employed in 138 patients (65%) and an unrelated donor in 73 (35%). The 10-year probabilities of overall and disease-free survival were 63.4% and 61%, respectively. The 10-year cumulative incidences of transplantation-related mortality and relapse were 15% and 24%, respectively. After 1999, no differences in either disease-free survival or transplant-related mortality were observed in patients transplanted from unrelated or matched family donors. In multivariate analysis, grade IV acute graft-versus-host disease was an independent factor associated with worse disease-free survival. By contrast, grade I acute graft-versus-host disease and age at diagnosis between 1 and 9 years were favorable prognostic variables. Our study, not intended to evaluate whether transplantation is superior to chemotherapy for children with acute lymphoblastic leukemia in first complete remission and high-risk features, shows that the allograft cured more than 60% of these patients; in the most recent period, the outcome of recipients of grafts from matched family and unrelated donors was comparable.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Sistema de Registros , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Itália/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Indução de Remissão , Fatores de Risco , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade , Resultado do TratamentoRESUMO
BACKGROUND: Extracorporeal photopheresis (ECP) is an effective treatment for both acute and chronic graft-versus-host disease (GVHD) in children and adults. Despite the large use of this treatment, a large heterogeneity in current application of ECP has been reported so far and recent evidence brought novel issues into some specific topics. Consensus-based recommendations ameliorate the appropriateness in daily clinical practice and, in turn, optimize the use of health care resources. STUDY DESIGN AND METHODS: Two Italian scientific societies, the Italian Society of Hemapheresis and Cell Manipulation (SIdEM) and the Italian Group for Bone Marrow Transplantation (GITMO), joined to develop and disseminate recommendations on appropriate application of ECP treatment in patients with GVHD. Accordingly, SIdEM and GITMO named an expert panel that first selected 16 questions that were considered relevant for clinical practice: the questions were subsequently addressed through a revision of the available literature and in consensus meetings. The whole group discussed the proposed recommendations according to the nominal group technique. RESULTS: The above-described approach in turn allowed the panel to agree on 47 practice recommendations. SIdEM and GITMO will disseminate such recommendations to the national transplant centers. CONCLUSION: In conclusion, SIdEM and GITMO have made a scientific effort to provide a useful tool to physicians involved in the field, thus supporting daily clinical practice, as well as strategic decisions in the setting of ECP treatment of GVHD.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Fotoferese , Adolescente , Adulto , Criança , Pré-Escolar , Consenso , Humanos , Lactente , Recém-Nascido , Itália , Pessoa de Meia-Idade , Sociedades MédicasRESUMO
Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) still represents a major challenge. We report the experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP) with allogeneic hematopoietic stem cell transplantation (HSCT) in children with Ph+ ALL from 1990 to 2008. Sixty-nine patients received HSCT from either a related (37, 54%) or an unrelated (32, 46%) donor. Twenty-five patients (36%) underwent transplantation before 2000 and 44 (64%) after 2000. Twenty-three patients (33%) received Imatinib mesylate treatment before HSCT and seven (10%) after HSCT. After a median follow-up of 56 months, the overall survival (OS) probability was 51% (95% confidence interval [CI], 38-63), the leukemia-free survival (LFS) was 47% (95% CI, 34-59), transplantation-related mortality (TRM) was 17% (95% CI, 10-30), and relapse incidence (RI) was 36% (95% CI, 26-50). Transplantation in first complete remission, female gender, and lower WBC count at diagnosis were associated with a better LFS in both univariate and multivariate analyses. Patients with p210 transcript had a trend for a worse prognosis compared with those who had the p190 transcript. Our series confirms the role of HSCT in the eradication of Ph+ ALL. Early HSCT is recommended once morphologic remission is obtained.
Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas , Criança , Pré-Escolar , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/imunologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Mesilato de Imatinib , Lactente , Itália , Masculino , Piperazinas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Pirimidinas/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Prevenção Secundária , Transplante Homólogo , Adulto JovemRESUMO
We analyzed risk factors influencing outcomes after related (R) human leukocyte antigen-identical cord blood transplantation (CBT) for 147 patients with malignancies reported to Eurocord-European Group for Blood and Marrow Transplantation. CBT has been performed since 1990; median follow-up was 6.7 years. Median patient age was 5 years. Acute leukemia was the most frequent diagnosis (74%). At CBT, 40 patients had early, 70 intermediate, and 37 advanced disease. CB grafts contained a median of 4.1 × 10(7)/kg total nucleated cells (TNCs) after thawing. The cumulative incidence (CI) of neutrophil recovery was 90% at day +60. CIs of acute and chronic graft-versus-host disease (GVHD) were 12% and 10% at 2 years, respectively. At 5 years, CIs of nonrelapse mortality and relapse were 9% and 47%, respectively; the probability of disease-free survival (DFS) and overall survival were 44% and 55%, respectively. Among other factors, higher TNCs infused was associated with rapid neutrophil recovery and improved DFS. The use of methotrexate as GVHD prophylaxis decreased the CI of engraftment. Patients without advanced disease had improved DFS. These results support banking and use of CB units for RCBT. Cell dose, GVHD prophylaxis not including methotrexate, and disease status are important factors for outcomes after RCBT.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Antígenos HLA/imunologia , Neoplasias Hematológicas/cirurgia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Humanos , Lactente , Leucemia/imunologia , Leucemia/mortalidade , Leucemia/cirurgia , Contagem de Leucócitos , Masculino , Análise Multivariada , Neutrófilos/citologia , Recidiva , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: A large heterogeneity in current mobilization and collection practices is perceived. Moreover, recent evidence introduced novel issues into some specific topics. Optimization of the clinical practice, through the adoption of clinical practice guidelines, previously proved to reduce health care resource use. STUDY DESIGN AND METHODS: Two Italian scientific societies, Società Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO), perceived the need of hematologists and transfusionists to share a common paradigm in the setting of hematopoietic stem cell transplantation (SCT). The aim of the current position paper is to provide common definitions and criteria for mobilization and collection of peripheral blood stem cells both in autologous and in the allogeneic setting. Current international and national standards (i.e., International Society of Hematotherapy and Graft Engineering) and recommendations (i.e., European Group for Blood and Marrow Transplantation) were harmonized with the Panel recommendations. RESULTS: The Expert Panel consisted of nine members (five transfusionists and four hematologists with both clinical and scientific experience of SCT in both pediatric and adult setting) and one methodologist and first convened on April 19, 2010: they in turn agreed on the questions to be answered by the project. Available literature was reviewed by one expert and the methodologist and presented to the other members. Statements were then formulated. SIDEM and GITMO planned an informal meeting of the Panel every 2 years to discuss relevant updates and possible changes to the recommendations. CONCLUSION: The efforts of the expert panel members allowed to set up and share a common approach to the mobilization, enumeration, and collection issues in the field of both autologous and allogeneic peripheral blood SCT.
Assuntos
Separação Celular/métodos , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico , Adulto , Remoção de Componentes Sanguíneos , Doadores de Sangue , Contagem de Células , Criança , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Transplante AutólogoRESUMO
BACKGROUND: Veno-occlusive disease (VOD) is a major complication following hematopoietic stem cell transplantation (HSCT). Its diagnosis is based on clinical criteria, which have a limited sensitivity. Increased plasminogen activator inhibitor-1 (PAI-1) levels have been suggested as a marker of VOD. We aimed to prospectively evaluate how the fibrinolytic parameters behaved to discriminate VOD from other liver disorders occurring after HSCT in a pediatric population. PROCEDURES: A total of 195 HSCT were performed on 161 children and VOD complicated 11 cases (6.8%). Alanine aminotransferase, total bilirubin, PAI-1 antigen (PAI-1:Ag) and activity, t-PA antigen, D-dimer, prothrombin time, activated partial thromboplastin time, antithrombin, fibrinogen, and platelet counts were measured in 105 HSCT before and then weekly for 1 month after HSCT. RESULTS: An early, significant increase in the fibrinolytic parameters was seen in patients who developed VOD, even before VOD was diagnosed clinically, by comparison with patients without complications or those with non-VOD liver disorders. The combined increase in bilirubin, D-dimer, and PAI-1:Ag levels beyond the normal range distinguished VOD cases from other liver complications with a high sensitivity and specificity. CONCLUSIONS: Our study demonstrates that fibrinolytic tests can help diagnose VOD after HSCT in the pediatric population.