RESUMEN
BACKGROUND: The prognosis of high-risk neuroblastoma stage 4 with bone marrow metastasis, MYCN amplified, or refractory neuroblastoma is poor. To date, no standard treatment has been established. In four selected cases, we challenged the killer-cell immunoglobulin-like receptor ligand mismatch cord blood transplantation in graft-versus-host disease (GVHD) with reduced-intensity conditioning. METHODS: Prior to this study, conventional chemotherapy, autologous peripheral blood stem cell transplantation with high-dose chemotherapy (busulfan and melphalan), surgery and radiation therapy were completed in every case. The status before cord blood transplantation in two cases was not complete remission (CR) and in the others it was CR. The primary site was the mediastinum, two adrenal glands and a retroperitoneum, respectively. Three patients had bone and bone marrow metastasis and one had MYCN amplification. In all cases, international neuroblastoma pathology classification was unfavorable histology. All patients were >2 years of age. RESULTS: Relapse occurred only in one patient 17 months after the last transplantation, and the other three patients maintained disease-free survival for 74, 36, and 24 months, respectively. In one case of relapse the disease could be controlled by conventional chemotherapy. Except one, all patients had no severe complications, such as acute or chronic GVHD. One patient had gastric antral vascular ectasia and hemorrhagic cystitis. CONCLUSION: This strategy might be feasible and should be investigated for efficacy in the future. No definite conclusion can be made, however, due to the very small number of patients. Further prospective studies are required to determine its efficacy.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/terapia , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Neoplasias del Mediastino/terapia , Neuroblastoma/terapia , Receptores KIR/inmunología , Neoplasias Retroperitoneales/terapia , Neoplasias de las Glándulas Suprarrenales/inmunología , Neoplasias de las Glándulas Suprarrenales/patología , Biomarcadores , Preescolar , Femenino , Humanos , Ligandos , Masculino , Neoplasias del Mediastino/inmunología , Neoplasias del Mediastino/patología , Neuroblastoma/inmunología , Neuroblastoma/patología , Neoplasias Retroperitoneales/inmunología , Neoplasias Retroperitoneales/patologíaRESUMEN
Hepatic SOS is a potentially life-threatening complication of conditioning for allogeneic HSCT. rTM is a new drug for treating DIC. We report our experience of the use of rTM as a prophylaxis against SOS in high-risk pediatric patients that underwent HSCT. We evaluated the cases of 19 pediatric hematology and oncology patients who underwent HSCT at our institution between 2007 and 2016. The patients who received HSCT after 2012 (n = 8) were treated with rTM as a prophylaxis against SOS together with UDCA and LMWH, whereas the others (n = 11) were only treated with UDCA and LMWH. Although SOS occurred by post-HSCT day 35 in 3 (27%) patients in the control group, SOS was not seen in the rTM group. Two of the former three patients suffered severe SOS, and one died of the condition. The mean peak level of PAI-1 (a marker of endothelial damage) was significantly lower in the rTM group. rTM appears to be a safe prophylaxis for SOS. The present findings suggest that prophylactic rTM after HSCT might help to prevent SOS.
Asunto(s)
Fibrinolíticos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/prevención & control , Trombomodulina/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Enfermedad Veno-Oclusiva Hepática/etiología , Humanos , Lactante , Recién Nacido , Masculino , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Overactive bladder (OAB) is a symptomatic syndrome defined by urinary urgency, usually accompanied by increased urination frequency and nocturia, with or without urinary incontinence. The prevalence of pediatric OAB in 5-13 year olds is as high as 16.6%, but the pathophysiology and epidemiology have not been sufficiently elucidated. METHODS: We retrospectively reviewed medical records in 117 children with OAB aged between 5 and 15 years during the years 2012-2016. At initial presentation, abdominal ultrasound and uroflowmetry were performed, and behavioral modifications, such as timed voiding, and constipation therapy were initiated. If there was no response after 4 weeks, antimuscarinic treatment was added. We evaluated the clinical features of OAB and factors related to the recovery period, which was defined as the period from the start of behavioral modifications to cure. RESULTS: The average recovery period was 11.9 ± 9.73 months. There was no significant difference in the recovery period according to age, gender, percentage of urination frequency, nocturnal enuresis, or constipation. The recovery period was significantly shorter in the group with bladder wall thickness ≥5 mm than with bladder wall thickness <5 mm. Children with a tower-shaped curve on uroflowmetry had a significantly shorter recovery period than those with a bell-shaped curve. CONCLUSIONS: Bladder wall thickness and uroflow curve shape are related to the recovery period of pediatric OAB.
Asunto(s)
Técnicas de Diagnóstico Urológico , Vejiga Urinaria Hiperactiva/diagnóstico , Urodinámica , Adolescente , Terapia Conductista , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía , Vejiga Urinaria Hiperactiva/fisiopatología , Vejiga Urinaria Hiperactiva/terapiaRESUMEN
A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein. Based on these findings, she was diagnosed with a lymphoblastic crisis of chronic myelogenous leukemia (CML). Combined chemotherapy, involving imatinib, resulted in complete molecular remission. She received cord blood transplant (CBT) during the first complete remission; she is alive and has not suffered a relapse since two years after the CBT. The sudden onset of a blastic crisis in pediatric CML is rare, and it may be difficult to distinguish such cases from de novo Ph-positive leukemia. For diagnostic purposes, it is essential to consider a patient's clinical course and blood test results.
Asunto(s)
Crisis Blástica/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Crisis Blástica/patología , Crisis Blástica/terapia , Niño , Femenino , Sangre Fetal/trasplante , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The combination of fludarabine (Flu), high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF; FLAG), with anthracyclines has become standard chemotherapy for refractory acute myeloid leukemia (AML) in European children and adults. To clarify the efficacy and the safety of FLAG-idarubicin (IDA) for children prospectively, we planned a multicenter phase II study (AML-R11) by the Japanese Pediatric Leukemia/Lymphoma Study Group. METHODS: Patients with AML aged between 2 and 20 years old, who had the first bone marrow (BM) relapse or induction failure, were enrolled. The FLAG-IDA regimen consisted of Flu 30 mg/m2 for 5 days, Ara-C 2 g/m2 for 5 days, G-CSF (lenograstim) 5 µg/kg for 6 days and IDA 10 mg/m2 for 3 days. The primary endpoint was remission rate after therapy. RESULTS: Due to drug supply issues, the trial was suspended after the inclusion of seven eligible patients. There were six cases of early relapse within 1 year of the first remission. All seven patients completed the therapy and no early death was observed. Hematological toxicity was common, and one patient developed grade 4 non-hematological toxicity of bacterial meningitis. Although only one patient with late relapse achieved complete remission, minimal residual disease was positive on both flow cytometry and Wilms' tumor 1 mRNA. Two patients were alive in remission following hematopoietic stem cell transplantation, whereas the other five patients died of either the disease or treatment-related causes. CONCLUSION: FLAG-IDA might be tolerable for children with refractory AML although the efficacy should be further investigated.
Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Idarrubicina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Vidarabina/análogos & derivados , Adolescente , Niño , Preescolar , Esquema de Medicación , Femenino , Humanos , Lenograstim , Masculino , Proteínas Recombinantes/uso terapéutico , Recurrencia , Resultado del Tratamiento , Vidarabina/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVES: To investigate renal concentrating ability after long-term fast-melting oral desmopressin lyophilisate treatment in children with monosymptomatic nocturnal enuresis. METHODS: The present retrospective study involved 58 children (43 boys, 15 girls; aged 6-12 years) with nocturnal enuresis receiving oral desmopressin lyophilisate. After treatment for 4 weeks with a complete response, patients were placed on a reduced dose of 120 µg on alternate days. Moring urine osmolality was measured using urine samples obtained after medication and non-medication dry nights. Patients who experienced ≥1 wet nights/month during alternate-day oral desmopressin lyophilisate treatment or within 6 months after its cessation were assigned to the relapse group, whereas those who experienced <1 wet night/month were assigned to the continued success group. RESULTS: The continued success and relapse groups included 41 and 17 patients, respectively. The mean duration of treatment was 18.5 and 18.3 months in the continued success group and relapse group, respectively. There was no significant difference in morning urine osmolality after medication nights between the continued success and relapse groups; however, morning urine osmolality after non-medication nights was significantly higher in the continued success group than in the relapse group (P < 0.0001). Similarly, nocturnal urine volume was significantly higher in the relapse group than in the continued success group (P = 0.046). CONCLUSIONS: These results suggest that patients receiving long-term oral desmopressin lyophilisate treatment develop increased nocturnal renal concentrating ability, which results in sustained dryness even after treatment cessation.
Asunto(s)
Fármacos Antidiuréticos/uso terapéutico , Desamino Arginina Vasopresina/uso terapéutico , Capacidad de Concentración Renal/efectos de los fármacos , Riñón/fisiopatología , Enuresis Nocturna/tratamiento farmacológico , Administración Oral , Fármacos Antidiuréticos/farmacología , Niño , Desamino Arginina Vasopresina/farmacología , Femenino , Humanos , Riñón/efectos de los fármacos , Capacidad de Concentración Renal/fisiología , Masculino , Enuresis Nocturna/fisiopatología , Concentración Osmolar , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Orina/químicaRESUMEN
Kasabach-Merritt syndrome (KMS) is characterized by hemangioma associated with life-threatening thrombocytopenia, and is a consumptive coagulopathy. Although treatments available include corticosteroids, α-interferon, vincristine, and surgery, response may be unsatisfactory, and the mortality rate remains at approximately 30%. Although radiotherapy has been used effectively for KMS, it may cause growth retardation and secondary malignancy. We report a case of KMS in which hemangioma of the left thigh was successfully treated with low-dose radiotherapy (6 Gy in six fractions, weekly) after failure of corticosteroid therapy. No significant late effects due to the radiotherapy were noted at 5 year follow up. Thus, low-dose radiotherapy remains an important treatment method for KMS when patients fail to respond to other treatments.
Asunto(s)
Síndrome de Kasabach-Merritt/radioterapia , Radioterapia de Intensidad Modulada/métodos , Humanos , Recién Nacido , Síndrome de Kasabach-Merritt/diagnóstico , Masculino , Tomografía Computarizada por Rayos XRESUMEN
The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Asparaginasa/administración & dosificación , Niño , Preescolar , Citarabina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Masculino , Inducción de Remisión , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We report a case of pediatric severe aplastic anemia (SAA), where the patient underwent allogenic bone marrow transplantation (BMT) from an HLA mismatched family donor and developed focal segmental glomerulosclerosis (FSGS). An 11-year-old girl, who had SAA, was admitted to our hospital in 200X. Complete remission was not attained after immunosuppressive therapy with rabbit-antithymocyte globulin, prednisolone (PSL), and cyclosporine A (CsA). Eight months after being diagnosed with SAA, she underwent an allogenic BMT from her mother. We used a combination of 2-Gy total body irradiation, fludarabine, and cyclophosphamide as a preparative regimen prior to the BMT. CsA and PSL were used as prophylaxis against GVHD. Since the BMT did not lead to successful engraftment, the patient required two peripheral blood stem cell transplantations (PBSCT). Engraftment was sustained and no acute or chronic GVHD was observed. Six months after the first BMT, she developed clinical nephrotic syndrome despite the continuous PSL and CsA treatments. Renal biopsy revealed a total of 12 glomeruli, one of which showed segmental sclerosis. Electron microscopy revealed diffuse effacement of the foot processes. These findings were consistent with FSGS, and she was treated with mycophenolate mofetil (MMF) in combination with PSL instead of CsA, which greatly reduced her proteinuria. In general, the most common type of nephropathy after HSCT is GVHD-related nephrotic syndrome, and the most common pathological finding is membranous nephropathy or minimal change. FSGS without GVHD after HSCT, such as that observed in our case, is rare. In this case, the renal damage appears to have been caused by the effect of circulating permeability factors with immunity change after HSCT. This case demonstrates the importance of renal biopsy as a guide to determine the extent of renal damage and as an aid to determine the possible response to therapy.
Asunto(s)
Anemia Aplásica/terapia , Glomeruloesclerosis Focal y Segmentaria/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Nefrótico/patología , Biopsia , Niño , Ciclosporina/uso terapéutico , Femenino , Glomeruloesclerosis Focal y Segmentaria/etiología , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Glomérulos Renales/ultraestructura , Microscopía Electrónica , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Síndrome Nefrótico/etiología , Proteinuria/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Adenina Fosforribosiltransferasa/deficiencia , Alopurinol/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Errores Innatos del Metabolismo/tratamiento farmacológico , Urolitiasis/tratamiento farmacológico , Alopurinol/uso terapéutico , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Inhibidores Enzimáticos/uso terapéutico , Femenino , HumanosRESUMEN
Adenine phosphoribosyltransferase (APRT) deficiency is an enzyme deficiency associated with purine metabolism, a hereditary disease that causes recurrent 2, 8-DHA stone formation due to a complete or partial APRT defect and slowly damages the renal function. Since APRT deficiency can be treated to prevent its progression to renal insufficiency, it is important to detect APRT gene mutations and make a definite diagnosis early. A 3.5-year-old girl presented with painful urination and dysuria, and was admitted to our hospital. The analysis of stones collected after spontaneous passage revealed 2, 8-dihydroxyadenine (DHA) urolithiasis. To make a definite diagnosis, we searched for the APRT gene mutations reported in Japanese. However, no APRT Q0 mutation was identified. Only a heterogeneous mutation, APRT J, was noted. Subsequently, we screened the gene mutation regions reported from Europe and the United States and identified a heterogeneous mutation at the start codon of APRT Q0 from methionine to valine. This is the first report of this mutation in Japan. She was diagnosed with APRT deficiency caused by a compound heterogeneous mutation: APRT Q0/(M1V) APRT J (M136T). We believe that the same gene mutation has been inherited among other Japanese. For the future genetic diagnosis of APRT deficiency, this is a valuable case.
Asunto(s)
Errores Innatos del Metabolismo/genética , Urolitiasis/genética , Adenina Fosforribosiltransferasa/deficiencia , Adenina Fosforribosiltransferasa/genéticaRESUMEN
Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Acondicionamiento Pretrasplante/métodos , Plaquetas/citología , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Recién Nacido , Japón , Masculino , Neutrófilos/citología , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento , Donante no Emparentado , Irradiación Corporal TotalRESUMEN
Group A rotavirus G-serotyping by polymerase chain reaction (PCR) using university hospital subject samples in September 2003 to August 2004, September 2004 to August 2005, September 2005 to August 2006, and September 2006 to August 2007 showed the most common serotypes G1 and G3, detected in 27 and 33 subjects, compared to 4 subjects in whom serotype G4 was detected. Between 2003 and 2004, serotypes G1 accounted for 50% and G3 for 38%, contrasting with serotype G3 at 79% between 2004 and 2005, serotype G1 at 91% between 2005 and 2006, and serotype G1 and G3 at 37% and 63% between 2006 and 2007, respectively. Serotypes G2 and G9 were not detected at all during any of our time periods. No correlation was seen between subject age and G serotype, although subjects younger than two years old accounted for 73% of subjects. This infection caused combined fever, diarrhea, and vomiting in 48% of subjects but showed no correlation with G serotype. These findings under-score the importance of G-serotyping in understanding rotavirus infection epidemiology at different times and in different locales.
Asunto(s)
Infecciones por Rotavirus/epidemiología , Factores de Edad , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Reacción en Cadena de la Polimerasa , Rotavirus , SerotipificaciónRESUMEN
Adenine phosphoribosyltransferase (APRT) deficiency is an enzyme deficiency associated with purine metabolism, a hereditary disease that causes recurrent 2, 8-DHA stone formation due to a complete or partial APRT defect and slowly damages the renal function. Since APRT deficiency can be treated to prevent its progression to renal insufficiency, it is important to detect APRT gene mutations and make a definite diagnosis early. A 3.5-year-old girl presented with painful urination and dysuria, and was admitted to our hospital. The analysis of stones collected after spontaneous passage revealed 2, 8-dihydroxyadenine (DHA) urolithiasis. To make a definite diagnosis, we searched for the APRT gene mutations reported in Japanese. However, no APRT Q0 mutation was identified. Only a heterogeneous mutation, APRT J, was noted. Subsequently, we screened the gene mutation regions reported from Europe and the United States and identified a heterogeneous mutation at the start codon of APRT Q0 from methionine to valine. This is the first report of this mutation in Japan. She was diagnosed with APRT deficiency caused by a compound heterogeneous mutation : APRT Q0/(M1V) APRT J (M136T). We believe that the same gene mutation has been inherited among other Japanese. For the future genetic diagnosis of APRT deficiency, this is a valuable case.
Asunto(s)
Adenina Fosforribosiltransferasa/genética , Adenina Fosforribosiltransferasa/deficiencia , Preescolar , Electroforesis en Gel de Agar , Femenino , Humanos , Errores Innatos del Metabolismo , Mutación , Análisis de Secuencia de ADN , Urolitiasis/etiología , Urolitiasis/genéticaRESUMEN
How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels. The CBI defined three groups that had different neutrophil engraftment rates at day 30 (High, 83.7% [95% CI, 79.2-88.1%]; Intermediate, 77.0% [95% CI, 73.7-80.2%]; Low, 68.4% [95% CI, 63.6-73.2%]), platelet engraftment rates at day 60 (High, 70.4% [95% CI, 64.9-75.9%]; Intermediate, 62.3% [95% CI, 58.5-66.0%]; Low, 49.3% [95% CI, 44.2-54.5%]), and non-relapse mortality at day 100 (High, 14.1% [95% CI, 9.9-18.3%]; Intermediate, 16.4% [95% CI, 13.5-19.3%]; Low, 21.3% [95% CI, 17.1-25.5%]). This novel approach is clinically beneficial and can be adopted immediately because it uses easily obtained pre-freeze data of CB.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Trasplante de Células Madre Hematopoyéticas , Antígenos CD34 , Sangre Fetal , Supervivencia de Injerto , Granulocitos , HumanosRESUMEN
Beckwith-Wiedemann syndrome (BWS) is characterized by an accumulation of multiple congenital anomalies. Although patients with BWS are known to have a higher incidence of embryonal tumors, there has been no reports associated with acute leukemia. This report describes the case of a patient with BWS who developed Acute Megakaryocytic Leukemia (AMKL,FAB;M7). Because most patients with BWS present gigantism, the therapy-related toxicity of chemotherapy can be a very serious problem. This patient exhibited no therapy-related toxicity after chemotherapy, suggesting that acute leukemia with BWS may not require a reduction in dosage.
Asunto(s)
Síndrome de Beckwith-Wiedemann/complicaciones , Leucemia Megacarioblástica Aguda/etiología , Humanos , Lactante , MasculinoRESUMEN
Prognosis in pediatric patients with refractory/relapsed acute myeloid leukemia (AML) is grim, and there is no standard treatment for such patients. Combined treatment with intensive chemotherapy and gemtuzumab ozogamicin (GO), a monoclonal anti-CD33 antibody conjugated with calicheamicin, is useful as reinduction therapy in refractory/relapsed AML. Here, we describe three cases of pediatric refractory/relapsed AML that were successfully managed with FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), with or without GO, as reinduction therapy before a KIR-ligand-mismatched cord blood transplant. This strategy relies on the fact that killer cell immunoglobulin-like receptors (KIR) on cord blood natural killer (NK) cells recognize human leukocyte antigen (HLA) class I alleles, and that donor KIR-ligand incompatibility may be associated with lower incidence of relapse and improved survival in AML, as cells that lack these inhibitory HLA ligands can activate NK cells. All three patients are currently alive and have been disease-free for 24-65 months, although one patient developed severe sinusoidal obstructive syndrome (SOS). Thus, our strategy can result in excellent outcomes in pediatric patients with refractory/relapsed AML.
RESUMEN
Rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (ADH5FDH ), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, Adh5-/-Aldh2 E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.
RESUMEN
Gastric antral vascular ectasia (GAVE) is an angiodysplastic disorder, which causes severe and prolonged gastric bleeding. Although GAVE has been described in adult patients treated with hematopoietic stem cell transplantation (HSCT), a few cases involving pediatric patients have also been reported. A 5-year-old boy with neuroblastoma (NB) developed severe hematemesis after undergoing tandem HSCT, i.e. autologous peripheral blood stem cell transplantation (auto-PBSCT), followed by allogeneic cord blood transplantation (allo-CBT). The patient suffered oral feeding difficulties because of the effects of chemotherapy and an unbalanced diet. Intravenous Busulfan (ivBU) was used as a conditioning regimen for the auto-PBSCT. The diagnosis of GAVE was made based on endoscopy of the upper gastrointestinal tract on day 31 after the allo-CBT. Argon plasma coagulation (APC) was performed twice, and the complete resolution of GAVE was confirmed by an endoscopic re-evaluation, conducted on day 87. GAVE in this case might have been associated with ivBU treatment. Atrophy of the gastric mucosa due to loss of appetite might also have contributed to GAVE. NB was treated using high-doses of alkylating agents, such as BU. Such treatment can cause significant mucositis of the oral cavity as well as vascular lesions and is associated with GAVE. Therefore, GAVE should be considered when gastrointestinal bleeding occurs in NB patients treated with HSCT. APC might be effective against HSCT-GAVE.