RESUMEN
Neuroblastomas are malignant tumors of the sympathetic nervous system. Areas of manifestation most commonly involve the abdomen, neck, thorax and pelvis. Primary renal neuroblastomas are extremely rare, only a few case reports exist worldwide, and even those are discussed controversially.We present the case of a 6-year-old girl with a renal tumor and a tumor thrombus extending into the right atrium, which radiologically appeared to be a Wilms tumor. Since the lesion did not respond to nephroblastoma-specific therapy, a biopsy from one of the liver metastases was taken, revealing the revised diagnosis of a clear cell renal cell carcinoma. Histopathology of the reference center, however, described a primary renal neuroblastoma. After adjusting the chemotherapy tumornephrectomy including the complete venous thrombus could be performed without any complications.Neuroblastoma originating from a kidney is an absolute rarity that can easily be misdiagnosed as Wilms tumor, especially, if a typical tumor thrombus with extension into the inferior vena cava is seen. Therefore neuronspecific enolase in serum as well as vanillylmandelic acid and homovanillic acid in the urine should be determined in all patients when Wilms tumor is assumed. To the best of our knowledge, this is the first published case of a primary renal neuroblastoma with a tumor thrombus extending into the right atrium.
Asunto(s)
Atrios Cardíacos/patología , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/secundario , Neoplasias Renales/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundario , Células Neoplásicas Circulantes/patología , Neuroblastoma/diagnóstico , Neuroblastoma/secundario , Niño , Diagnóstico Diferencial , Femenino , Neoplasias Cardíacas/patología , Humanos , Riñón/patología , Neoplasias Renales/patología , Hígado/patología , Neoplasias Hepáticas/patología , Pulmón/patología , Neoplasias Pulmonares/patología , Neuroblastoma/patologíaRESUMEN
Radionecrosis (RN) in children treated for brain tumors represents a potentially severe long-term complication. Its diagnosis is challenging, since magnetic resonance imaging (MRI) cannot clearly discriminate between RN and tumor recurrence. A retrospective single-center study was undertaken to describe the incidence and clinical course of RN in a cohort of 107 children treated with external radiotherapy (RT) for various brain tumors between 1992 and 2012. During a median follow-up of 4.6 years (range 0.29-20.1 years), RN was implied by suspicious MRI findings in in 5 children (4.7 %), 5-131 months after RT. Suspicion was confirmed histologically (1 patient) or substantiated by FDG positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR spectroscopy (1 patient). Before developing RN, all 5 patients had received cytotoxic chemotherapy in addition to RT. In addition to standard treatment protocols, 2 patients had received further chemotherapy for progression or relapse. Median radiation dose expressed as the biologically equivalent total dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0-60.0 Gy). At RN onset, 4 children presented with neurological symptoms. Treatment of RN included resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids, hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN was not treated. Complete radiological regression of the lesions was observed in all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed permanent severe neurological deficits. RN represents a severe long-term treatment complication in children with brain tumors. The spectrum of clinical presentation is wide; ranging from asymptomatic lesions to progressive neurological deterioration. FDG-PET and MR spectroscopy may be useful for distinguishing between RN and tumor recurrence. Treatment options in patients with symptomatic RN include conservative management (steroids, HBO, bevacizumab) and surgical resection.
Asunto(s)
Lesiones Encefálicas/epidemiología , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/radioterapia , Traumatismos por Radiación/epidemiología , Radioterapia Conformacional/estadística & datos numéricos , Adolescente , Austria/epidemiología , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Incidencia , Lactante , Estudios Longitudinales , Masculino , Medición de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Intensification of antileukemic treatment and progress in supportive management have improved the survival rates of children with acute myeloid leukemia (AML). However, morbidity and early mortality in these patients are still very high, especially in children with acute monoblastic leukemia (AML FAB M5). Inflammatory syndromes complicating the management of these children after application of cytosine arabinoside and due to hyperleukocytosis at initial presentation have been reported. Hemophagocytic lymphohistiocytosis (HLH) has been described as a serious and life-threatening acute complication during treatment of different oncologic entities; however, data on HLH in children with AML FAB M5 are extremely rare. METHODS: A retrospective study of all children with AML FAB M5 treated at our institution between 1993 and 2013 was performed to describe the clinical characteristics of patients who developed an inflammatory syndrome with HLH during oncologic treatment. RESULTS: Three of 10 children developed an inflammatory syndrome with fever, elevation of C-reactive protein, hyperferritinemia, elevation of soluble interleukin-2, and hemophagocytosis during prolonged aplasia following the first cycle of chemotherapy not responding to broad-spectrum antibiotics. No infectious agents could be identified; the initial symptoms occurred 17, 18, and 28 days after diagnosis of AML, respectively. The children immediately responded to dexamethasone; however, the same syndrome was observed again after the second cycle of chemotherapy and, in one patient, also after the third cycle. CONCLUSIONS: Treating physicians should be aware of an inflammatory syndrome resembling HLH in children with monoblastic leukemia since this problem might extremely complicate management and supportive care of these children. The co-incidence of monoblastic leukemia with HLH might be explained by cytokines released from the monoblastic leukemic cells themselves.
Asunto(s)
Fiebre de Origen Desconocido/patología , Leucemia Monocítica Aguda/patología , Linfohistiocitosis Hemofagocítica/patología , Adolescente , Adulto , Proteína C-Reactiva/metabolismo , Niño , Preescolar , Femenino , Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/metabolismo , Humanos , Interleucina-2/metabolismo , Leucemia Monocítica Aguda/metabolismo , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/metabolismo , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenAsunto(s)
Eritema Pernio/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/terapia , Lupus Eritematoso Discoide/terapia , Pancitopenia/terapia , Eritema Pernio/etiología , Preescolar , Glucocorticoides/uso terapéutico , Humanos , Leucemia Mieloide Aguda/complicaciones , Lupus Eritematoso Discoide/complicaciones , Masculino , Pancitopenia/etiología , Trasplante HomólogoRESUMEN
Two related boys who died from fulminant infectious mononucleosis were diagnosed with X-linked lymphoproliferative disease type 1 (XLP-1). Family screening (n=17) identified 6 female mutation carriers and 2 more XLP-1 patients in whom, despite recurrent infections, agammaglobulinemia, and Hodgkin's Disease, the genetic basis had been unknown; demonstrating that awareness and early genetic testing are crucial to reveal underlying primary immunodeficiencies and improve outcome. Furthermore, XLP should be included routinely in the differential diagnosis of severe hypogammaglobulinemia and/or lymphoma in males.
Asunto(s)
Mononucleosis Infecciosa/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Linfohistiocitosis Hemofagocítica/genética , Trastornos Linfoproliferativos/genética , Adolescente , Agammaglobulinemia/diagnóstico , Agammaglobulinemia/genética , Preescolar , Análisis Mutacional de ADN , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/genética , Exones/genética , Resultado Fatal , Tamización de Portadores Genéticos , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Pruebas Genéticas , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Humanos , Lactante , Mononucleosis Infecciosa/diagnóstico , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/mortalidad , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/mortalidad , Masculino , Meningoencefalitis/complicaciones , Meningoencefalitis/diagnóstico , Meningoencefalitis/genética , Mutación Missense , Linaje , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Adulto JovenRESUMEN
BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.
Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/terapia , Enfermedad Injerto contra Huésped/terapia , Sarcoma de Ewing/mortalidad , Sarcoma de Ewing/terapia , Trasplante de Células Madre , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Acanthamoeba is the causative agent of granulomatous amebic encephalitis, a rare and usually fatal disease. We report a child with acute lymphoblastic leukemia who developed brain abscesses caused by Acanthamoeba during induction therapy. Multimodal antimicrobial chemotherapy and hyperbaric oxygen therapy resulted in complete resolution of symptoms and of pathology as seen by magnetic resonance imaging.
Asunto(s)
Acanthamoeba/aislamiento & purificación , Amebiasis/diagnóstico , Antiprotozoarios/uso terapéutico , Infecciones Protozoarias del Sistema Nervioso Central/diagnóstico , Oxígeno/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Acanthamoeba/genética , Amebiasis/parasitología , Encéfalo/diagnóstico por imagen , Absceso Encefálico/diagnóstico , Absceso Encefálico/parasitología , Infecciones Protozoarias del Sistema Nervioso Central/parasitología , Preescolar , ADN Protozoario/química , ADN Protozoario/genética , Encefalitis/diagnóstico , Encefalitis/parasitología , Humanos , Imagen por Resonancia Magnética , Masculino , Datos de Secuencia Molecular , Radiografía , Análisis de Secuencia de ADN , Resultado del TratamientoRESUMEN
Parvovirus B19 (PVB19) induced severe aplastic anaemia (SAA) or myelodysplastic syndrome (MDS) is rare, and haematopoietic stem cell transplantation (HSCT) in this condition has not been reported so far. 6 children with SAA (n=4) or MDS (n=2) caused by acute PVB19 infection underwent HSCT under the protection of intravenous immunoglobulines. The 4 children with SAA received matched HLA bone marrow from a sibling (n=3) or peripheral unrelated blood stem cells (n=1). 1 patient had delayed erythrocyte engraftment, whereas 3 patients had an uneventful transplantation course. HSCT in one of the 2 children with MDS was complicated by poor graft function, the other patient engrafted without complications. In conclusion, HSCT in children with PVB19 induced SAA or MDS is feasible, even though some patients may develop delayed engraftment or prolonged poor graft function.
Asunto(s)
Anemia Aplásica/terapia , Eritema Infeccioso/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Síndromes Mielodisplásicos/terapia , Parvovirus B19 Humano , Adolescente , Trasplante de Médula Ósea , Niño , Funcionamiento Retardado del Injerto/diagnóstico , Estudios de Factibilidad , Femenino , Humanos , Inmunización Pasiva , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Childhood immune thrombocytopenia (ITP) is a bleeding disorder characterized by decreased platelet counts. Assessment of the individual bleeding risk during the course of the disease would allow more accurately guiding treatment-related decisions in these patients. PATIENTS AND METHODS: We conducted a pilot study and prospectively evaluated platelet counts and bleeding signs using an established bleeding (Buchanan) score in 30 patients with newly diagnosed ITP at 3 different time points (at diagnosis [TP1], on day 2-3 [TP2], and on day 5-8 [TP3]) during the first week after diagnosis. 15 patients received immune modulatory therapy. RESULTS: Median platelet counts at the 3 different time points were 13, 19, 32×10 (9)/L (untreated patients) and 2, 7, 37×10 (9)/L (treated patients). Corresponding median cumulative bleeding scores were 5, 2, 0 (untreated patients) and 7, 6, 2 (treated patients). Cumulative median bleeding scores and platelet counts were inversely correlated in treated and untreated patients at all 3 time points. Cumulative median bleeding scores significantly decreased in both groups. CONCLUSIONS: Bleeding signs in children with newly diagnosed ITP rapidly improve within one week after diagnosis. Serial grading of bleeding severity seems to be useful to comprehensively assess and monitor the individual bleeding risk in these patients, but has to be evaluated and validated in a larger cohort.
Asunto(s)
Hemorragia/diagnóstico , Hemorragia/inmunología , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/inmunología , Corticoesteroides/uso terapéutico , Niño , Preescolar , Terapia Combinada , Femenino , Hemorragia/terapia , Humanos , Inmunización Pasiva , Masculino , Proyectos Piloto , Recuento de Plaquetas , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/terapiaRESUMEN
To evaluate the human herpes virus 6 (HHV-6) -specific immune response in individuals with chromosomally integrated HHV-6 (ciHHV-6), we measured HHV-6-antigen-specific cytokine responses (interferon-γ, interleukin-2, tumour necrosis factor-α) in T cells by flow cytometry in 12 and 16 individuals with and without ciHHV-6, respectively. All individuals with ciHHV-6 showed HHV-6-specific T cells with higher frequencies of HHV-6-specific CD8(+) cells (0.03-14.93, median 2.15% of CD8(+) cells) compared with non-ciHHV-6 (0.0-10.67, median 0.36%, p 0.026). The observed increased HHV-6-specific functionally active responses in individuals with ciHHV-6 clearly disprove speculations on immune tolerance in ciHHV-6 and indicate clinical and immunological implications of ciHHV-6.
Asunto(s)
Citocinas/metabolismo , Herpesvirus Humano 6/genética , Infecciones por Roseolovirus/virología , Linfocitos T/citología , Adulto , Anciano , Anciano de 80 o más Años , Cromosomas Humanos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Roseolovirus/genética , Infecciones por Roseolovirus/inmunología , Linfocitos T/metabolismo , Integración Viral , Adulto JovenRESUMEN
Chronic immune thrombocytopenia (cITP) is often associated with an underlying predisposition towards autoimmunity, recognition of which is relevant to guide treatment. International recommendations on diagnostic steps and therapeutic measures of cITP in childhood exist. However, due to the low prevalence (1-2/100,000) and a variation of availability of immunological and hematological tests and treatments across pediatric units, we postulated that these guidelines are not uniformly adhered to and that immune dysregulation syndromes remained undiscovered. To delineate the current management of children and adolescents with cITP in Austria, we performed a nationwide cross-sectional study. Between 2011 and 2014, 81 children with cITP were seen at seven centers (median age 8.75 years; range 1-17; female:male ratio 47:34) at 641 visits during 180 patient years after diagnosis of cITP (>12 months ITP duration). Additional diagnoses were noted, most frequently immune or autoimmune disorders, hematologic diseases, or infections (in 37.3%, including Evans syndrome, autoimmune lymphoproliferative syndrome, systemic lupus erythematosus, and Fanconi anemia), or other symptoms like bi- or pancytopenia (n=9), lymphoproliferation or granulomatous inflammation (n = 3). Both decision to treat as well as choice of treatment varied: smaller centers tended to observe more frequently, larger centers applied a pattern of treatment modalities that appeared to depend less on bleeding tendency than on center policy. More than 50% of therapeutic interventions occurred in bleedings scores ≤2 (of 5), suggesting a strong psychosocial intention to treat. Platelet increment upon 479 therapeutic interventions of eight types was evaluated, with multiple treatment approaches being pursued sequentially in refractory patients. These data confirm the hypothesis of heterogeneous diagnostic and therapeutic management of cITP in Austrian children and corroborate the need for (1) a precise panel of parameters to exclude underlying disorders and (2) for biomarkers to predict treatment response.
Asunto(s)
Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adolescente , Austria , Niño , Preescolar , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Lactante , MasculinoRESUMEN
Conditioning including total body/lymphoid irradiation is widely used to prevent graft rejection in patients with refractory severe aplastic anemia (SAA) undergoing hemopoietic cell transplantation (HCT) from alternative donors and or after graft manipulation. To reduce regimen-related toxicity we transplanted three children with refractory SAA after conditioning with radiotherapy-free regimens. Conditioning included fludarabine 175-180 mg/m2 in all patients. In addition, patient 1 (failing two previous grafts) received thiotepa 10 mg/kg and Campath-1H 60 mg/m2; patient 2 cyclophosphamide 120 mg/kg, thiotepa 15 mg/kg and OKT-3 0.1 mg/kg/day for 4 weeks; and patient 3 cyclophosphamide 120 and ATG 90 mg/kg. Stem cell source was unmanipulated marrow from the same unrelated donor as for the two previous transplantations in patient 1 and CD34+-purified peripheral blood stem cells from an HLA-matched unrelated donor and from the haploidentical mother in patients 2 and 3. Only patient 1 received graft-versus-host disease (GVHD) prophylaxis with cyclosporine A and mycophenolate mofetil. Follow-up is now 30, 51, and 15 months. None of the patients developed GVHD. All patients have normal counts with complete donor chimerism. Fludarabine-based conditioning is powerfully immunosuppressive and may be used for children with refractory SAA undergoing HCT from alternative donors even after rejection following previous HCT.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Donantes de Tejidos , Trasplante Homólogo , Vidarabina/administración & dosificaciónRESUMEN
Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, myelodysplastic syndrome and nonmalignant diseases, who received αß T- and B-cell-depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and serotherapy with OKT3 or ATG-Fresenius. Graft manipulation was carried out with anti-TCRαß and anti-CD19 Abs and immunomagnetic microbeads. The γδ T cells and natural killer cells remained in the grafts. Primary engraftment occurred in 88%, acute GvHD (aGvHD) grades II and III-IV occurred in 10% and 15%, respectively. Immune recovery data were available in 26 patients and comparable after OKT3 (n=7) or ATG-F (n=19). Median time to reach >100 CD3+ cells/µL, >200 CD19+ cells/µL and >200 CD56+ cells/µL for the whole group was 13, 127 and 12.5 days, respectively. Compared with a historical control group of patients with CD34+ selected grafts, significantly higher cell numbers were found for CD3+ at days +30 and +90 (267 vs 27 and 397 vs 163 cells/µL), for CD3+4+ at day +30 (58 vs 11 cells/µL) and for CD56+ at day +14 (622 vs 27 cells/µL). The clinical impact of this accelerated immune recovery will be evaluated in an ongoing prospective multicenter trial.
Asunto(s)
Antígenos CD19 , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Depleción Linfocítica/instrumentación , Síndromes Mielodisplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos de Linfocitos T alfa-beta , Recuperación de la Función/inmunología , Acondicionamiento Pretrasplante/métodos , Adolescente , Aloinjertos , Linfocitos B/inmunología , Niño , Preescolar , Femenino , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/terapia , Estudios Retrospectivos , Linfocitos T/inmunología , Donantes de TejidosRESUMEN
Hematopoietic progenitor cell levels were monitored in the peripheral blood of ten healthy adults receiving a single dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF). The objective was to determine the time and number of progenitor cells released into the peripheral blood, induced by a single dose of 15 micrograms/kg rhG-CSF administered intravenously. In all cases the absolute number of circulating progenitor cells including granulocyte-macrophage and erythroid lineages increased up to 12-fold (median 9.4-fold) 4 days after treatment. These findings were based on flow cytometric quantification of CD34+ cells and on progenitor assays. The relative distribution of granulocyte/macrophage and erythroid progenitors remained unchanged. rhG-CSF was well tolerated; mild to moderate bone pain was the most common side-effect and was noted in 6 of 10 subjects. Thus a single dose of rhG-CSF is effective in mobilizing progenitor cells into the peripheral blood in healthy adults. If these progenitors are capable of reconstituting bone marrow, peripheral progenitor cell separation following rhG-CSF administration could be a reasonable alternative to conventional bone marrow harvest in healthy adults.
Asunto(s)
Factores Estimulantes de Colonias/farmacología , Células Madre Hematopoyéticas/citología , Adulto , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Recuento de Leucocitos , Masculino , Proteínas Recombinantes/farmacologíaRESUMEN
Bone marrow transplantation plays an essential role in the successful treatment of both juvenile and adult chronic myelogenous leukemia. Recently, it has been reported that conditioning with high doses of busulfan can successfully replace total body irradiation (TBI), in patients with acute myelogenous leukemia as well as adult chronic myelogenous leukemia. We report here the case of a 29-month-old boy with juvenile chronic myelogenous leukemia (JCML) transplanted with HLA-identical bone marrow after conditioning with busulfan, etoposide and cyclophosphamide. Successful engraftment was followed by early relapse on day 67. A second HLA-identical transplant was performed following myeloablative treatment with TBI. Engraftment was once again successful and the patient remains free of disease more than 24 months after transplantation. We conclude that busulfan is insufficient in eradicating JCML and that TBI is required prior to transplantation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Busulfano/administración & dosificación , Preescolar , Ciclofosfamida/administración & dosificación , Humanos , Masculino , Recurrencia , Inducción de Remisión/métodos , Trasplante Homólogo , Irradiación Corporal TotalRESUMEN
Treatment with antibodies against T-lymphocytes usually triggers a febrile response potentially mimicking or masking infection. Procalcitonin (PCT) is considered a sensitive and specific marker of systemic bacterial and fungal infection. It was the aim of this study to investigate the characteristics of PCT and C-reactive protein (CRP) during treatment with polyclonal or monoclonal anti-T-cell antibodies, in order to examine the ability of these parameters to distinguish between systemic bacterial infection and reaction to antibody treatment. Thus, 15 consecutive febrile episodes after T-cell antibody infusion without clinical signs of infection were compared with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gram-negative sepsis. Therefore, during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release.
Asunto(s)
Anticuerpos/efectos adversos , Proteína C-Reactiva/análisis , Calcitonina/sangre , Fiebre/etiología , Precursores de Proteínas/sangre , Sepsis/diagnóstico , Adolescente , Anticuerpos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Biomarcadores/sangre , Péptido Relacionado con Gen de Calcitonina , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Fiebre/diagnóstico , Bacterias Gramnegativas , Humanos , Lactante , Masculino , Neoplasias/complicaciones , Neoplasias/terapia , Sensibilidad y Especificidad , Linfocitos T/inmunologíaRESUMEN
A paediatric patient was treated with orthotopic liver transplantation after he developed cirrhosis of the liver due to chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. His pre-existing chronic GVHD of the skin disappeared and immunosuppressive therapy could be gradually tapered and finally withdrawn 71 months after liver transplantation. Two and a half years after discontinuation of all immunosuppressive therapy, the patient is in excellent condition with neither signs of chronic GVHD nor rejection of the liver graft.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/terapia , Tolerancia Inmunológica , Trasplante de Hígado , Anemia Sideroblástica/complicaciones , Anemia Sideroblástica/terapia , Cadáver , Enfermedad Crónica , Humanos , Lactante , Cirrosis Hepática/etiología , Cirrosis Hepática/terapia , Masculino , Inmunología del Trasplante , Trasplante Homólogo/efectos adversosRESUMEN
We report two children who presented with cough and shortness of breath 7-8 months after a matched sibling stem cell transplant (SCT) for chronic myelogenous leukemia and myelodysplastic syndrome, respectively. Pulmonary function tests (PFTs) revealed severe airways obstruction (AO). However, radiographic investigations showed no serious abnormalities in the early phase and open lung biopsy revealed only mild lymphocytic bronchiolitis and bronchiolitis obliterans consistent with pulmonary graft-versus-host disease (GVHD). Despite administration of bronchodilators and various immunosuppressive agents obstructive lung disease progressed to pulmonary failure in patient 1, whereas stabilization of the clinical course was observed in patient 2. Serial PFTs were the best predictor of the clinical course in contrast to radiographic and histologic findings. It is concluded that PFTs should be performed repeatedly in pediatric patients after allogeneic SCT with the aim of diagnosing GVHD-associated AO in the subclinical phase. Progressive post-transplant AO necessitates prompt initiation of intensive immunosuppressive therapy in order to stop the underlying immunopathologic process even in the absence of severe radiographic and histologic findings.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Enfermedades Pulmonares , Síndromes Mielodisplásicos/terapia , Adolescente , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/diagnóstico por imagen , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/fisiopatología , Prueba de Histocompatibilidad , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/fisiopatología , Masculino , Radiografía , Trasplante HomólogoRESUMEN
Three children with refractory severe aplastic anemia were transfused with high numbers of unrelated matched (n = 2) or C-locus haploidentical mismatched (n = 1) CD34-selected peripheral blood stem cells in the absence of an HLA-identical family donor. Two leukaphereses of the donors yielded a median number of 10.1 x 10(10) nucleated cells (range 9.7-15.4) with a median number of 9.89 x 10(8) CD34+ cells (range 7.46-26.1) and a median percentage of CD34+cells of 0.98% (range 0.77-1.7). After positive selection by magnetic cell sorting the patients received a median of 14.3 x 10(6) CD34+ cells/kg (range 11.7-24.3) and of 1.3 x 10(4) CD3+ cells/kg (range 0.57-5.8). Median time to ANC >/=0.5 x 10(9)/l was 7 days (range 7-12) and to platelets >/=20 x 10(9)/l 13 days (range 13-27). Chimerism analysis of peripheral blood after transplantation revealed permanent 100% donor hematopoiesis in all patients. The patient with the C-locus haploidentical mismatch presented with acute GVHD (grade III-IV) of the skin, liver and lower gastrointestinal tract (onset day +40) and died despite intensive immunosuppressive treatment on day +238. The two survivors developed lymphopoietic recovery of B and T lymphocytes within 3 months after transplantation. To our knowledge this experience represents the first report of transplantation with unrelated CD34+ enriched peripheral blood stem cell in children with refractory severe aplastic anemia. Bone Marrow Transplantation (2000) 25, 513-517.
Asunto(s)
Anemia Aplásica/terapia , Antígenos CD34/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Anemia Aplásica/complicaciones , Antígenos CD/análisis , Antígenos CD34/sangre , Relación CD4-CD8 , Niño , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucaféresis/métodos , Recuento de Linfocitos , Masculino , Células Madre/inmunología , Factores de Tiempo , Donantes de Tejidos , Quimera por Trasplante , Trasplante HomólogoRESUMEN
Stem cell transplantation is the only curative approach to the treatment of Wiskott-Aldrich syndrome. However, using grafts from partially matched unrelated donors is associated with increased risk of graft rejection and graft-versus-host disease. In an attempt to prevent these problems, a 6-year-old boy with Wiskott-Aldrich syndrome lacking a suitable family donor, was transplanted with large numbers of unrelated highly purified CD34+ peripheral blood stem cells mismatched at one C locus. Conditioning consisted of busulfan 16 mg/kg body weight, cyclophosphamide 200 mg/kg body weight and antithymocyte globulin 20 mg/kg body weight x 3 days. The boy had a rapid hematopoietic engraftment and showed immunologic reconstitution by day +92. Although he did not receive prophylactic immunosuppression he did not develop any graft-versus-host disease and is well and alive up to now, 25 months after transplantation.