RESUMEN
TCF3-HLF-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has an extremely poor prognosis. A 2-year-old boy with TCF3-HLF-positive BCP-ALL had an isolated extramedullary relapse in multiple bones after allogeneic hematopoietic stem cells transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor. In this study, he received a T-cell-replete haploidentical HSCT (TCR-haplo-HSCT) from his father when in nonremission state, which resulted in a sustained complete remission for over 3 years. Immune therapies for patients with an extramedullary relapse of TCF3-HLF-positive BCP-ALL have been attempted; however, long-term efficacies of these therapies remain unknown. Our TCR-haplo-HSCT may be an effective therapeutic option for such patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Preescolar , Trasplante de Médula Ósea , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos T , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia , Enfermedad Aguda , Receptores de Antígenos de Linfocitos T , Estudios Retrospectivos , Donante no Emparentado , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Proteínas de Fusión OncogénicaRESUMEN
Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bacteriemia/prevención & control , Mortalidad Hospitalaria/tendencias , Hospitalización/estadística & datos numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Adulto , Bacteriemia/epidemiología , Bacteriemia/microbiología , Causas de Muerte , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Japón/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Haploidentical hematopoietic stem cell transplantation (HSCT) is a useful therapy for relapsed/refractory acute leukemia or lymphoma because of the strong graft-vs-leukemia (GVL) effect. However, it is often accompanied by severe acute graft-versus-host disease (aGVHD), which is the most serious complication after haploidentical HSCT. Thus, it is important to control the severity of aGVHD while maintaining the GVL effect. In our experience of pediatric haploidentical HSCT, it takes several days for aGVHD to become severe after the appearance of initial symptoms, mostly skin rashes. In this study, we aimed to identify useful biomarkers at the onset of aGVHD that predict subsequent development of severe aGVHD. METHODS: Forty-five consecutive children with relapsed/refractory acute leukemia or lymphoma who developed aGVHD after haploidentical HSCT were enrolled. We analyzed possible biomarkers from samples collected at the onset of acute GVHD. RESULTS: Nineteen patients developed grade 1-2 aGVHD, and 26 patients developed grade 3-4 aGVHD. There was no significant difference in patient characteristics between the two groups. Transplant-related mortality occurred only in the grade 3-4 aGVHD group (34.5%). Multivariate analysis revealed that serum albumin was an independent biomarker for predicting the severity of aGVHD (P = 0.009). The area under the receiver operating characteristic curve of serum albumin was 0.864. CONCLUSIONS: The serum albumin level at the onset of aGvHD could be a useful biomarker for the development of subsequent severe aGVHD in pediatric patients after haploidentical HSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia , Enfermedad Aguda , Niño , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Albúmina SéricaRESUMEN
Sinusoidal obstruction syndrome (SOS), also called veno-occlusive disease (VOD) of the liver, is one of the most relevant complications of hepatic sinusoidal endothelial origin that appears early after hematopoietic cell transplantation (HCT). Despite its relatively low incidence and the spontaneous resolution of most SOS/VOD cases, severe SOS/VOD evolved to multi-organ failure with an >80% mortality rate and represents one of the major clinical problems after HCT. The sinusoidal endothelial cells and hepatocytes are damaged by toxic metabolites generated by the conditioning regimen in these patients. Several risk factors have been identified for SOS/VOD development. Although defibrotide is recommended for both prevention and treatment, no satisfactory therapy exists for managing severe SOS/VOD. Thus, this review describes the new definition of SOS/VOD diagnosis and the severity grading of suspected SOS/VOD from the European Society for Blood and Marrow Transplantation. Furthermore, it describes the results of current treatment including the Japanese therapeutic use program, defibrotide treatment protocol.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Células Endoteliales , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/tratamiento farmacológico , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Polidesoxirribonucleótidos/uso terapéutico , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL). PROCEDURE: Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21 years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated. To assess survival, we developed a scoring system using significant adverse pre-HSCT variables. RESULTS: Overall, 247 patients died. The median length of follow up among survivors was 1145 days, and the 3-year overall survival was 22% (95% confidence interval [CI]: 18-27%). A low performance score, presence of >25% bone marrow blasts, T-cell phenotype, poor-risk or normal cytogenetics, and history of HSCT were predictors of a poor outcome. Patients scoring 0-1 (n = 109), 2 (n = 91), and 3-7 (n = 125) had a 3-year overall survival of 41% (95% CI: 31-51%), 21% (95% CI: 13-31%), and 7% (95% CI: 3-12%), respectively. CONCLUSION: These results support HSCT in certain nonremission patients. Even in patients without complete remission, outcomes differed according to pre-HSCT factors. A scoring system could help determine the appropriateness of HSCT in children and adolescents with nonremission ALL.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto JovenRESUMEN
Mismatched HLA loss is a cause of leukemia relapse after HLA-haploidentical stem cell transplantation (haplo-SCT). We report a patient with a history of 2 occurrences of leukemia relapse due to mismatched HLA loss after haplo-SCT. He received haplo-SCT from his father but showed leukemia relapse with loss of the maternal HLA haplotype. He then underwent haplo-SCT from his mother, and developed relapse with loss of the paternal HLA haplotype. Both donors had killer cell immunoglobulin-like receptor-ligand mismatch but alloreactive natural killer cells could not prevent relapse. Second haplo-SCT should be conducted carefully for patients with relapse due to mismatched HLA loss.
Asunto(s)
Antígenos HLA/inmunología , Histocompatibilidad/inmunología , Células Asesinas Naturales/inmunología , Recurrencia Local de Neoplasia/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores KIR/inmunología , Trasplante de Células Madre/efectos adversos , Adolescente , Femenino , Efecto Injerto vs Leucemia/inmunología , Humanos , Masculino , Recurrencia Local de Neoplasia/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Autotolerancia/inmunología , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Almost all pediatric patients with renal tumors are diagnosed with nephroblastoma (Wilms tumor), clear cell sarcoma, or malignant rhabdoid tumor. The choice of treatment is important for relapsed and refractory patients with nephroblastoma. Furthermore, clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK) have a poor prognosis compared with nephroblastoma. Thus, stem cell transplantation (SCT) is sometimes selected to treat these tumors. PATIENTS AND METHODS: The authors targeted a total of 84 patients with nephroblastoma, CCSK, and MRTK who underwent a first autologous SCT between 1992 and 2014, and were registered in the Japanese Transplant Registry Unified Management Program system. The authors retrospectively analyzed the SCT data for survival rate. RESULTS: Five-year overall survival rates for nephroblastoma, CCSK, and MRTK were 72.4%±6.3%, 46.8%±13.8%, and 36.4%±14.5%, respectively. The event-free survival rates at 5 years were 64.9%±6.7%, 35.7%±12.8%, and 27.3%±13.4%, respectively. The relapse rates at 5 years were 25.3%±11.4%, 46.2%±28.4%, and 60.0%±43.1%, respectively. CONCLUSION: Although the survival rate for nephroblastoma was relatively high, those of CCSK and MRTK were poor.
Asunto(s)
Neoplasias Renales , Sistema de Registros , Trasplante de Células Madre , Tumor de Wilms , Adolescente , Adulto , Autoinjertos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Tumor de Wilms/mortalidad , Tumor de Wilms/terapiaRESUMEN
Predictors of peripheral blood stem cell (PBSC) yield can potentially improve the comfort, safety, and efficacy of CD34+ cell collection from donors treated with recombinant human granulocyte colony-stimulating factor (G-CSF). We investigated 181 apheresis procedures on 109 healthy allogeneic donors to identify factors correlating with efficient PBSC collection. Apheresis started on Day 4 or 5 and continued up to Day 6 of G-CSF administration. CD34+ cellãyields on Days 4 and 5 were comparable, and significantly higher than on Day 6. This suggests that starting apheresis on Day 4 rather than Day 5 may be preferable, to reduce G-CSF exposure and optimize yield, even if multi-day collection is required. More CD34+ cells were collected from male and cytomegalovirus (CMV)-seronegative donors than from female and CMV-seropositive donors, respectively. The yields of CD34+ cells were similarly high in both male and female donors aged 20-29 years; yields decreased in female donors in their thirties, and were comparably low in both male and female donors in their forties and thereafter. These findings should guide decision-making about when to begin apheresis, and encourage careful consideration of donor factors such as gender, age, and CMV serostatus when collecting PBSCs.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Factor Estimulante de Colonias de Granulocitos/inmunología , Células Madre de Sangre Periférica/inmunología , Adulto , Donantes de Sangre , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Few clinical trials have been reported for patients with intermediate-risk neuroblastoma because of the scarcity of the disease and the variety of clinical and biological characteristics. A multidisciplinary treatment that consists of multidrug chemotherapy and surgery is expected to lead to a good prognosis with few complications. Therefore, a clinical trial for patients with intermediate-risk tumors was designed to establish a standard treatment that reduces complications and achieves good outcomes. METHODS: We planned a prospective phase 2, single-arm study of the efficacy of image-defined risk factors (IDRF)-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. For the localized tumor group, IDRF evaluations will be performed after each three-course chemotherapy, and surgery will be performed when appropriate. For patients with metastatic tumors, a total of five chemotherapy courses will be performed, and primary lesions will be removed when the IDRF becomes negative. The primary endpoint is 3-year progression-free survival rate, and the secondary endpoints include 3-year progression-free survival rates and overall survival rates of the localized group and the metastasis group and the incidence of adverse events. From international results, 75% is considered an appropriate 3-year progression-free survival rate. If this trial's expected 3-year progression-free survival rate of 85% is statistically greater than 75% in the lower limit of the 95.3% confidence interval, with an accuracy 10% (85 ± 10%), both groups require more than 65 patients. DISCUSSION: This study is the first clinical trial on the efficacy of IDRF-based surgical decision and stepwise treatment intensification for patients with intermediate-risk neuroblastomas. We expect that this study will contribute to the establishment of a standard treatment for patients with intermediate-risk neuroblastoma. TRIAL REGISTRATION: UMIN000004700, jRCTs051180203; Registered on December 9, 2010.
Asunto(s)
Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Humanos , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/cirugía , Estudios Prospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
AIM: To study the probability of developing secondary brain tumors after cranial radiotherapy.Background Patients treated with cranial radiotherapy are at risk for developing secondary brain tumors. PATIENTS AND METHODS: We planned an institutional survey for secondary brain tumors in survivors after cranial irradiation and reviewed the 30-year duration data. Event analysis and cumulative proportion curves were performed to generally estimate the cumulative proportion of developing secondary brain tumors, cavernoma and meningioma at different periods of time. RESULTS: Secondary brain tumors occurred in 21% of cases: 10% were cavernomas, 6% were meningiomas, 3% were skull osteomas, and 1% were anaplastic astrocytoma. The cumulative proportion of developing secondary brain tumor was 6% at 10 years and 20% at 20 years, while the cumulative proportion for developing cavernomas and meningiomas was 16% and 7% at 20 years, respectively. CONCLUSION: Our study shows that patients who received cranial irradiation were at risk of secondary brain tumors such as cavernomas and meningiomas. Thus, a meticulous follow-up of cancer survivors with history of cranial irradiation by an annual MRI scan is justifiable. This will help clinicians to detect secondary brain tumors early and make its management much easier.
RESUMEN
BACKGROUND: The present study sought to reduce the incidence of treatment complications of low-risk neuroblastoma by using image-defined risk factors (IDRFs) to inform the timing of surgical resection. PROCEDURES: Eligible patients included children (<18 years of age) with stage 1 or 2 disease, children (<365 days of age) with stage 3 disease, and infants with stage 4S disease. In IDRF-negative cases, treatment was completed with surgical resection alone. In IDRF-positive cases, the timing of surgery was determined based on the IDRFs after low-dose chemotherapy with 2-3 of the following four drugs: vincristine, cyclophosphamide, pirarubicin, and carboplatin. The outcome measures were overall survival, progression-free survival, and adverse events. This study was registered with the UMIN Clinical Trials Registry (number 000004355). RESULTS: Of the 60 patients screened between 2010 and 2013, 58 eligible patients were enrolled; 32 were identified as IDRF negative at diagnosis while 26 were identified as IDRF positive and underwent induction chemotherapy. The 3-year overall and progression-free survival rates of the 58 patients were 100% and 82.8% (95% confidence interval: 70.3-90.3), respectively. Neutropenia was the most frequently reported grade 3 or 4 chemotherapy-related form of toxicity (41.7%). With regard to surgical complications, 2.5% of all patients developed pleural effusion and ascites as early complications, while only 2.5% developed renal atrophy as a long-term complication. No fatal toxicities were observed. CONCLUSION: Using IDRFs to inform surgical decision making for the treatment of low-risk neuroblastoma improved prognosis and reduced the incidence of long-term complications.
Asunto(s)
Neuroblastoma/cirugía , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/etiología , Niño , Preescolar , Toma de Decisiones Clínicas , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Femenino , Ganglioneuroblastoma/diagnóstico por imagen , Ganglioneuroblastoma/tratamiento farmacológico , Ganglioneuroblastoma/cirugía , Humanos , Lactante , Recién Nacido , Japón , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/tratamiento farmacológico , Derrame Pleural/etiología , Complicaciones Posoperatorias/etiología , Supervivencia sin Progresión , Estudios Prospectivos , Factores de Riesgo , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Enfermedades Vasculares/etiología , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
BACKGROUND: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. METHODS: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. RESULTS: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. CONCLUSIONS: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Sistema de Registros , Encuestas y Cuestionarios , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Incidencia , Lactante , Japón/epidemiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Prospectivos , Inducción de Remisión/métodos , Tasa de Supervivencia/tendenciasRESUMEN
Long-term survival rates for pediatric patients with cancer have significantly improved, but novel approaches are desired for those with refractory/relapsed solid tumors. Recently, programed cell death-1/programed cell death-ligand-1 blockade has emerged as an effective option for many intractable cancers. However, not all patients show objective response to such therapy. On the other hand, several other checkpoint pathways, including Herpes virus entry mediator (HVEM)/B- and T-lymphocyte attenuator (BTLA), galectin-9 (GAL9)/T-cell immunoglobulin and mucin domain-3 (TIM3), and major histocompatibility complex class II (MHC-II)/lymphocyte activation gene-3 (LAG3), also regulate immune responses in the tumor microenvironment and may be alternative targets for novel immune therapies. In this study, we examined 65 common pediatric solid tumors and characterized the expression of Herpes virus entry mediator, GAL9, and MHC-II on tumor cells and their corresponding receptors B- and T-lymphocyte attenuator, TIM3, and LAG3, respectively, on tumor-infiltrating lymphocytes (TILs) with immunohistochemistry. Whereas the expression of GAL9 and MHC-II was limited, 73% of rhabdomyosarcomas and 100% of osteosarcomas expressed moderate to high levels of Herpes virus entry mediator on the tumor. TILs were detected in all tumor samples except one osteosarcoma. Interestingly, 45% of rhabdomyosarcomas, and 45% of osteosarcomas expressed moderate to high levels of both Herpes virus entry mediator on the tumor cells and B- and T-lymphocyte attenuator on the TILs. Results showed that a subset of pediatric solid tumors expressed tumor-associated checkpoint molecules, and TILs expressed corresponding receptors for these checkpoint molecules. Thus, immunogenic environments may be created, and checkpoint blockade may induce favorable immune responses.
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Linfocitos B/inmunología , Neoplasias Óseas/inmunología , Proteínas de Neoplasias/inmunología , Osteosarcoma/inmunología , Rabdomiosarcoma/inmunología , Linfocitos T/inmunología , Adolescente , Linfocitos B/patología , Neoplasias Óseas/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Osteosarcoma/patología , Rabdomiosarcoma/patología , Linfocitos T/patologíaRESUMEN
Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT. The 3-year probability of overall survival and event-free survival was 75.0 and 62.5%, respectively. These results indicate the efficacy of TCR-haplo-HSCT for relapsed/refractory pediatric Ph-ALL.
Asunto(s)
Resistencia a Antineoplásicos , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Recurrencia Local de Neoplasia/terapia , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos T/inmunología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Estudios Retrospectivos , Terapia Recuperativa , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR-haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced-intensity re-conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow-up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow-up. These results suggested that a TCR-haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF.
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Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Linfocitos T/trasplante , Trasplante Haploidéntico/métodos , Adolescente , Niño , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Epstein-Barr virus-related post-transplantation lymphoproliferative disease (EBV-PTLD) is a serious complication in hematopoietic stem cell transplantation (HSCT) recipients. METHODS: We conducted a retrospective study to investigate the incidence and potential risk factors for EBV reactivation and to assess the efficacy of the management of EBV reactivation with pre-emptive rituximab in children who had T-cell-replete haploidentical HSCT (TCR-haplo-SCT) with low-dose anti-thymocyte globulin (ATG). EBV-DNA level in peripheral blood (PB) was measured when suspected EBV reactivation were observed. When the EBV-DNA level in PB increased to >1,000 copies/106 peripheral blood mononuclear cells (PBMC), patients were pre-emptively treated with rituximab (375 mg/m2 /dose). RESULTS: A total of 19 (50%) of 38 patients received rituximab infusion at a median time of 56 days after HSCT (range, 17-270 days). The median viral load at initiation of therapy was 2,900 copies/106 PBMC (range, 1,000-650 000). Pre-emptive therapy was started after a median of 2 days (range, 0-7 days). The median number of weekly treatment cycles was 2 (range, 1-3). None of the patients developed PTLD or other EBV-associated diseases. CONCLUSION: Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG.
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Infecciones por Virus de Epstein-Barr/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores Inmunológicos/uso terapéutico , Rituximab/uso terapéutico , Trasplante Haploidéntico/efectos adversos , Adolescente , Niño , Preescolar , Esquema de Medicación , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/virología , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Incidencia , Lactante , Infusiones Intravenosas , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Carga ViralRESUMEN
We describe the case of a 13-year-old girl with multifocal disseminated Ewing sarcoma family of tumor (ESFT) who received a 5/8 human leukocyte antigen-matched haploidentical hematopoietic cell transplantation to generate a graft-versus-tumor effect. The patient had grade 2 acute graft-versus-host disease (GVHD) of the skin and chronic GVHD nausea and abdominal pain that required prednisolone for 17 months, but has been free from ESFT for 3 years 10 months after therapy. The present case suggests a beneficial effect of haploidentical hematopoietic cell transplantation in disseminated ESFT.
Asunto(s)
Neoplasias Óseas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Huesos Pélvicos , Sarcoma de Ewing/terapia , Adolescente , Femenino , Enfermedad Injerto contra Huésped , HumanosRESUMEN
BACKGROUND: Hematopoietic stem cell transplantation (HSCT)-related nephrotic syndrome (NS) is a rare event and has been described as a clinical form of chronic graft-versus-host disease (GVHD). Although immunological mechanisms are thought to play important roles in NS after HSCT, the exact mechanisms have not been clarified. CASE-DIAGNOSIS/TREATMENT: We report a 4-year-old boy with acute lymphoblastic leukemia (ALL) who developed NS during the tapering of immunosuppressants 5 months after an allogeneic HSCT (allo-HSCT). A renal biopsy was performed, and light and electron microscopy revealed minimal change disease (MCD). Although the response to treatment with steroids and tacrolimus was favorable, the child experienced two relapses of NS within the first 9 months after the initial response. A second allo-HSCT was performed to treat the relapse of ALL. After the second allo-HSCT, the remission of NS was maintained without recurrence for 5 years, even after the cessation of immunosuppressants. CONCLUSIONS: Our patient who had ALL and developed NS after his first allo-HSCT, maintained remission from NS after a second allo-HSCT. This suggests that the immune cells from the first donor origin were associated with the pathogenesis of NS.
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Enfermedad Injerto contra Huésped/cirugía , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Nefrótico/cirugía , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Preescolar , Enfermedad Crónica , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/inmunología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Recurrencia , Reoperación , Factores de Tiempo , Trasplante Homólogo , Resultado del TratamientoRESUMEN
BACKGROUND: Pediatric apheresis for peripheral blood stem cell transplantation should be carried out with due concern for low corporeal blood volume and vulnerability to hypocalcemia-related complications, hypovolemic shock, and hypervolemic cardiac overload. STUDY DESIGN AND METHODS: We retrospectively investigated a total of 267 apheresis procedures from 1990 to 2013 on 93 children between 0 and 10 years old, including 89 patients and 4 healthy donors, with body weights of 6.3 to 44.0 kg. RESULTS: The median CD34+ cell yield per apheresis procedure was 2.3 × 106 CD34+ cells/kg (0.2-77.9 × 106 CD34+ cells/kg). Adverse events occurred in 11.6% of procedures (n = 31), including mild perivascular pain (n = 12), emesis (n = 9), hypotension (n = 3), urticaria (n = 2), numbness (n = 2), chest pain (n = 1), facial flush (n = 1), and abdominal pain (n = 1). Among hypotensive events, shock in a 9.6 kg one-year-old boy required emergency treatment in 1996. Thereafter, we adopted continuous injection of calcium gluconate, ionized calcium monitoring, central venous catheter access and circuit priming with albumin in addition to concentrated red cells. Since then we have had fewer complications: 16.4% per apheresis during 1990-1997 versus 5.8% during 1998-2013. No healthy pediatric donors suffered from any late-onset complications related to apheresis or G-CSF administration. CONCLUSION: By employing appropriate measures, peripheral blood stem cell apheresis for small children can have an improved safety profile, even for children weighing <10 kg.
Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Movilización de Célula Madre Hematopoyética/métodos , Atención al Paciente/métodos , Células Madre de Sangre Periférica/citología , Antígenos CD34/metabolismo , Eliminación de Componentes Sanguíneos/efectos adversos , Donantes de Sangre , Presión Sanguínea , Peso Corporal/efectos de los fármacos , Calcio/administración & dosificación , Calcio/farmacología , Niño , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Dolor/etiología , Células Madre de Sangre Periférica/efectos de los fármacosRESUMEN
Idiopathic hyperammonemia (IHA) has been described as a complication of intensive chemotherapy for the treatment of hematologic malignancy but has subsequently been found in patients undergoing bone marrow transplantation and in those with solid tumors treated with 5-fluorouracil. Although IHA is a rare complication, it is sometimes associated with high mortality in hematologic malignancies. Here we report the case of a 15-year-old boy in whom hyperammonemia developed during the initial treatment with prednisolone for newly diagnosed acute lymphoblastic leukemia and who survived after early detection and oral lactulose therapy. To the best of our knowledge, this is the first report of IHA that was not induced by intensive chemotherapy, stem cell transplantation, or asparaginase therapy in a patient with newly diagnosed leukemia, but developed during an initial treatment with a steroid. Early detection of IHA by measuring the plasma ammonia level in patients with neurological symptoms may improve the outcome.