RESUMEN

Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes.

Asunto(s)

Anemia de Fanconi/complicaciones , Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Busulfano/uso terapéutico , Niño , Preescolar , Anemia de Fanconi/mortalidad , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo , Irradiación Corporal Total/efectos adversos , Irradiación Corporal Total/mortalidad , Adulto Joven

RESUMEN

Infection by human adenoviruses can lead to significant morbidity and mortality in immunocompromised hosts, such as allogeneic stem cell transplant (SCT) recipients, with limited effective treatment options. Specific cutaneous manifestations of disseminated adenovirus infection are not well described. We report a woman in her twenties who received an allogeneic T-cell-depleted peripheral blood SCT for the treatment of severe aplastic anaemia and, 5 months post-transplant, was hospitalized for severe systemic adenovirus infection with progressive involvement of the colon, liver and lungs. Despite therapy with intravenous cidofovir, oral brincidofovir and intravenous immunoglobulin, she had progression of adenoviraemia and dissemination of adenoviral disease. The patient developed a progressive rash characterized by keratotic papules that began on the palms and soles and spread to the entire body. Histopathological examination of skin biopsies of individual skin lesions from the palm and abdomen showed focal acantholytic dyskeratosis and keratinocytes with hyperchromatic nuclei. Several keratinocyte nuclei were immunoreactive for adenovirus. The patient was further treated with ribavirin and adenovirus-specific cytotoxic T lymphocytes but experienced multisystem progression of adenovirus infection culminating in death.

RESUMEN

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.

Asunto(s)

Trasplante de Células Madre de Sangre del Cordón Umbilical , Tracto Gastrointestinal/inmunología , Enfermedad Injerto contra Huésped/terapia , Antígenos HLA/inmunología , Neoplasias Hematológicas/terapia , Agonistas Mieloablativos/uso terapéutico , Acondicionamiento Pretrasplante , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Budesonida/uso terapéutico , Calcineurina/metabolismo , Inhibidores de la Calcineurina , Niño , Preescolar , Inhibidores Enzimáticos/uso terapéutico , Femenino , Tracto Gastrointestinal/patología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/métodos , Linfocitos T/inmunología , Trombocitopenia/terapia , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Humanos , Lectinas de Plantas/uso terapéutico , Proteínas de Soja/uso terapéutico , Linfocitos T/efectos de los fármacos , Donante no Emparentado

RESUMEN

T-cell depleted allogeneic hematopoietic SCT (TCD-HSCT) have shown durable disease-free survival with a low risk of GVHD in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) before transplant transplant. Median follow-up of surviving patients is 6 years. The 10-year OS and EFS were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. OS (P=0.01) correlated with the sAAIPI. The incidence of grades II-IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/mortalidad , Depleción Linfocítica/mortalidad , Linfoma no Hodgkin , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Depleción Linfocítica/efectos adversos , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Quimera por Trasplante , Trasplante Homólogo , Adulto Joven

RESUMEN

Impairment of glucose metabolism (in particular insulin resistance and type 2 diabetes mellitus) has been reported in patients who have undergone hematopoietic SCT (HSCT) during childhood, especially those treated with TBI. This pilot study was conducted to determine prevalence of and possible underlying mechanisms for impaired glucose homeostasis in young adults treated with HSCT and TBI and who were not previously known to have diabetes mellitus. A total of 10 subjects (6 males, 4 females) were evaluated. Mean ages were 13.0+/-1.0 years at the time of TBI and 24.0+/-1.1 years at the time of this study. Five subjects had laboratory evidence of insulin resistance using the homeostasis model assessment and the quantitative insulin sensitivity check index indices. Two of these subjects had impaired fasting glucose and four had decreased plasma insulin-like growth factor 1 levels. All 10 subjects had evidence of abdominal obesity. Insulin resistance is frequently observed in adult survivors of HSCT treated with TBI in childhood. Underlying mechanisms may include radiation-induced growth hormone deficiency and changes in body composition.

Asunto(s)

Intolerancia a la Glucosa/etiología , Homeostasis/efectos de la radiación , Resistencia a la Insulina , Sobrevivientes , Acondicionamiento Pretrasplante/efectos adversos , Irradiación Corporal Total/efectos adversos , Adolescente , Adulto , Glucemia/análisis , Índice de Masa Corporal , Irradiación Craneana/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Intolerancia a la Glucosa/epidemiología , Trasplante de Células Madre Hematopoyéticas , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Obesidad Abdominal/complicaciones , Proyectos Piloto , Prevalencia , Adulto Joven

RESUMEN

Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.

Asunto(s)

Anticuerpos Monoclonales/administración & dosificación , Resistencia a Medicamentos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunoglobulina G/administración & dosificación , Enfermedad Aguda , Adolescente , Adulto , Anticuerpos Monoclonales Humanizados , Causas de Muerte , Niño , Preescolar , Daclizumab , Evaluación de Medicamentos , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/inducido químicamente , Estudios Retrospectivos , Esteroides/farmacología , Trasplante Homólogo

RESUMEN

Impaired linear growth has been shown to occur in individuals treated during childhood with single-dose and fractionated total body irradiation (TBI) before stem cell transplantation. Our objective was to describe the final heights attained and patient/treatment factors correlating with final height in a cohort of childhood cancer survivors treated with hyperfractionated TBI (total dose 1375 or 1500 cGy). Thirty individuals (18 men) were included in the study. The mean final height standard deviation score (s.d.s.) was -1.9 +/- 0.2, significantly lower than height s.d.s. at TBI (-0.2 +/- 0.2, P < 0.001). Final height s.d.s. was significantly correlated with age at diagnosis, age at TBI and target height (P = 0.04, P < 0.001, P < 0.001, respectively). Treatment with growth hormone (GH) (n = 7) maintained mean height s.d.s. at -2.0 from the onset of GH therapy until attainment of final height. The mean final sitting height s.d.s. was -2.2 +/- 0.2 (n = 16), significantly shorter than mean final standing height s.d.s. (P < 0.01). In conclusion, treatment with hyperfractionated TBI is associated with a reduction in standing height and an even greater reduction in sitting height. Final height after hyperfractionated TBI was similar to that reported after fractionated TBI.

Asunto(s)

Estatura , Neoplasias/terapia , Trasplante de Células Madre , Acondicionamiento Pretrasplante , Irradiación Corporal Total , Adulto , Niño , Preescolar , Femenino , Crecimiento/efectos de la radiación , Humanos , Lactante , Masculino , Neoplasias/radioterapia , Padres , Selección de Paciente , Trasplante Autólogo , Trasplante Homólogo , Irradiación Corporal Total/métodos

RESUMEN

PNH is characterized by expansion of one or more stem cell clones with a PIG-A mutation, which causes a severe deficiency in the expression of glycosylphosphatidylinositol (GPI)-anchored proteins. There is evidence that the expansion of PIG-A mutant clones is concomitant with negative selection against PIG-A wild-type stem cells by an aplastic marrow environment. We studied 36 patients longitudinally by serial flow cytometry, and we determined the proportion of PNH red cells and granulocytes over a period of 1-6 years. We observed expansion of the PNH blood cell population(s) (at a rate of over 5% per year) in 12 out of 36 patients; in all other patients the PNH cell population either regressed or remained stable. The dynamics of the PNH cell population could not be predicted by clinical or hematologic parameters at presentation. These data indicate that in most cases the PNH cell expansion has already run its course by the time of diagnosis. In addition, since in most cases no further expansion takes place, we can infer that the tendency to overgrow normal cells is not an intrinsic property of the PNH clone.

Asunto(s)

Hematopoyesis , Hemoglobinuria Paroxística/fisiopatología , Adolescente , Adulto , Médula Ósea/patología , Antígenos CD59/metabolismo , Niño , Células Clonales , Eritrocitos/patología , Femenino , Citometría de Flujo , Granulocitos/patología , Células Madre Hematopoyéticas/química , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad

RESUMEN

Respiratory syncytial virus, one of the most common causes of respiratory infections in immunocompetent individuals, is frequently spread to recipients of HSCT by family members, other patients, and health care workers. In immunosuppressed individuals, progression from upper respiratory tract disease to pneumonia is common, and usually fatal if left untreated. We performed a retrospective analysis of RSV infections in recipients of autologous or allogeneic transplants. The incidence of RSV following allogeneic or autologous HSCT was 5.7% and 1.5%, respectively. Of the 58 patients with an RSV infection, 16 of 21 patients identified within the first post-transplant month, developed pneumonia. Seventy-two percent of patients received aerosolized ribavirin and/or RSV-IGIV, including 23 of 25 patients diagnosed with RSV pneumonia. In this aggressively treated patient population, three patients died of RSV disease, each following an unrelated HSCT.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Virus Sincitial Respiratorio/etiología , Infecciones del Sistema Respiratorio/etiología , Adolescente , Adulto , Aerosoles , Anciano , Antivirales/administración & dosificación , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Terapia de Inmunosupresión/efectos adversos , Masculino , Persona de Mediana Edad , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/etiología , Neumonía Viral/terapia , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/terapia , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/terapia , Estudios Retrospectivos , Ribavirina/administración & dosificación , Trasplante Autólogo , Trasplante Homólogo

RESUMEN

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.

Asunto(s)

Aberraciones Cromosómicas , Hemoglobinuria Paroxística/genética , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Células Madre Hematopoyéticas/patología , Hemoglobinuria Paroxística/patología , Hemoglobinuria Paroxística/terapia , Humanos , Cariotipificación , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Topotecan appears to be relatively unaffected by the most common multidrug resistance mechanisms, may potentiate cytotoxicity of alkylators, has good penetration into the central nervous system, is active against a variety of neoplasms, and has myelosuppression as its paramount toxicity. We present our experience with a myeloablative regimen that includes topotecan. Twenty-one patients with poor-prognosis tumors and intact function of key organs received topotecan 2 mg/m2 by 30-min intravenous (i.v.) infusion on days -8, -7, -6, -5, -4; thiotepa 300 mg/m2 by 3 h i.v. infusion on days -8, -7, -6; and carboplatin by 4 h i.v. infusion on days -5, -4, -3 with a daily dose derived from the pediatric Calvert formula, using a targeted area under the curve of seven mg/ml* min ( approximately 500 mg/m2/day). Stem cell rescue was on day 0. The patients were 1 to 29 (median 4) years old; 18 were in complete remission (CR) and three in partial remission (PR). Early toxicities were severe mucositis and erythema with superficial peeling in all patients and a seizure, hypertension, and renal insufficiency followed by veno-occlusive disease in one patient each. Post-transplant treatment included radiotherapy alone (four patients) or plus biological agents (11 patients with neuroblastoma). With a follow-up of 6+ to 32+ (median 11+) months, event-free survivors include 10/11 neuroblastoma patients (first CR), 4/5 brain tumor patients (second PR or CR), 1/3 patients with metastatic Ewing's sarcoma (first or second CR), and a patient transplanted for multiply recurrent immature ovarian teratoma; a patient with desmoplastic small round-cell tumor (second PR) had progressive disease at 8 months. Favorable results for disease control, manageable toxicity, and the antitumor profiles of topotecan, thiotepa, and carboplatin, support use of this three-drug regimen in the treatment of neuroblastoma and brain tumors; applicability to other tumors is still uncertain.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carboplatino/administración & dosificación , Neuroblastoma/tratamiento farmacológico , Tiotepa/administración & dosificación , Topotecan/administración & dosificación , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Niño , Preescolar , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Masculino , Neuroblastoma/complicaciones , Neuroblastoma/terapia , Radioterapia Adyuvante , Inducción de Remisión , Resultado del Tratamiento

RESUMEN

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.

Asunto(s)

Antivirales/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Retinitis por Citomegalovirus/virología , Citosina/análogos & derivados , Citosina/uso terapéutico , Farmacorresistencia Viral , Encefalitis Viral/virología , Foscarnet/uso terapéutico , Ganciclovir/uso terapéutico , Huésped Inmunocomprometido , Organofosfonatos , Compuestos Organofosforados/uso terapéutico , Ventrículos Cerebrales/virología , Niño , Cidofovir , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/fisiopatología , Combinación de Medicamentos , Farmacorresistencia Viral/genética , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/fisiopatología , Femenino , Humanos

RESUMEN

Abnormalities of endocrine function and growth are common following stem cell transplantation in the pediatric/adolescent population. Impaired linear growth and adult short stature are associated with younger age at transplant, use of TBI and prior cranial irradiation, and development of chronic GvHD. Primary hypothyroidism is the most common abnormality of the thyroid and is observed in 10-28% of cases following fractionated TBI. Autoimmune hyperthyroidism has also been described post-stem cell transplant and most often results from adoptive transfer of abnormal clones of T or B cells from donor to recipient. Gonadal dysfunction is extremely prevalent and includes oligo-azoospermia in the majority of males treated with TBI, and primary ovarian failure in most women treated with TBI or Busulfan/Cyclophosphamide. Leydig cell function, however, is retained in most males treated with standard forms of cytoreduction. Many patients demonstrate reduced bone mineral density and are at risk of developing osteoporosis in the future.

Asunto(s)

Enfermedades del Sistema Endocrino/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Niño , Femenino , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/fisiopatología , Humanos , Hipotálamo/fisiopatología , Masculino , Osteoporosis/etiología , Hipófisis/fisiopatología , Reproducción/efectos de los fármacos , Reproducción/efectos de la radiación , Enfermedades de la Tiroides/etiología , Irradiación Corporal Total/efectos adversos

RESUMEN

BACKGROUND: Chronic lung disease and pulmonary failure are complications that can occur after bone marrow transplantation (BMT) and are associated with severe morbidity and mortality. METHODS: We report on four patients who developed chronic, progressive, and irreversible lung disease 1 to 3 years after allogeneic BMT in childhood. These patients had chronic graft-versus-host disease (n=3) or radiation-related pulmonary fibrosis (n=1). Three patients underwent double lung transplants and one patient underwent a single lung transplant 2 to 14 years after BMT. RESULTS: All four patients tolerated the lung transplantation procedure well and showed significant clinical improvement with normalization of pulmonary function tests by 1 year posttransplant. One patient died from infectious complications 3 years after lung transplantation, and one patient died after chronic rejection of the transplanted lungs 6 years posttransplant. Two patients remain alive without significant respiratory impairment 2 and 7 years after lung transplantation. CONCLUSION: We conclude that lung transplantation offers a viable therapeutic option for patients who develop respiratory failure secondary to BMT.

Asunto(s)

Trasplante de Médula Ósea/efectos adversos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Adolescente , Adulto , Niño , Preescolar , Resultado Fatal , Humanos , Masculino , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

Epilepsia partialis continua (EPC) is a condition defined by prolonged focal myoclonus. Often resistant to therapy, EPC in children is frequently present in Rasmussen encephalitis, a form of chronic encephalitis of uncertain etiology. We discuss a child who developed bilateral EPC 5 months after a bone marrow transplant. Neuroimaging studies showed signal abnormalities on both sensory-motor areas. An extensive search failed to reveal the etiology of the disorder, but treatment with a broad-spectrum anti-viral agent was associated with resolution of the process. An unidentified infectious agent may be responsible for an encephalitis of the motor strip in immunosuppressed patients.

Asunto(s)

Trasplante de Médula Ósea/efectos adversos , Encefalitis/etiología , Epilepsia Parcial Continua/etiología , Niño , Encefalitis/terapia , Epilepsia Parcial Continua/terapia , Humanos , Masculino

RESUMEN

We have employed a new cytoreductive regimen to transplant two patients with Fanconi anaemia (FA), using T cell-depleted two HLA-allele disparate related peripheral blood stem cell transplants (PBSCTs). Patient 1, a 5-year-old male with FA and aplastic anaemia, initially received an HLA two-antigen mismatched unrelated cord blood transplant and failed to engraft. He received fludarabine (Flu) and cyclophosphamide (Cy), followed by a CD34(+) E-rosette(-) (CD34(+)E(-)), T cell-depleted, granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCT from his HLA B-DRB1 mismatched father. He received anti-thymocyte globulin (ATG), steroids, FK506 and G-CSF after transplant for rejection and graft-versus-host disease (GVHD) prophylaxis. The patient is now 23 months after SCT with no evidence of GVHD and with full haematopoietic and immune reconstitution. Patient 2, a 10-year-old boy with FA and myelodysplastic syndrome, received single-dose total body irradiation (SDTBI), Flu and Cy followed by a CD34(+)E(-), T-cell-depleted, G-CSF-mobilized PBSCT from his HLA B-DRB1 mismatched sister. He also received ATG, steroids, FK506 and G-CSF after transplant. The patient is now 12 months after SCT in complete remission with no evidence of GVHD. Absolute neutrophil counts (ANC) of > 1 x 10(9)/l were achieved on day 11 and day 10 post transplant respectively. Both patients are fully engrafted. In summary, we report two successful T-cell-depleted stem cell transplants from mismatched related donors for the treatment of Fanconi anaemia, using a fludarabine-based cytoreduction. Both patients experienced minimal toxicity, rapid engraftment and no GVHD.

Asunto(s)

Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Depleción Linfocítica/métodos , Linfocitos T/inmunología , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Preescolar , Ciclofosfamida/uso terapéutico , Anemia de Fanconi/inmunología , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Proteínas Recombinantes , Tacrolimus/administración & dosificación

RESUMEN

PURPOSE: A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively RESULTS: The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 x 10(9)/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 x 10(9)/L (DFS, 73% v35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%). CONCLUSION: In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.

Asunto(s)

Antineoplásicos/uso terapéutico , Trasplante de Médula Ósea , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento

RESUMEN

The association of an acute reversible encephalopathy with transient occipital lobe abnormalities on imaging studies is well known. This condition has been called reversible posterior leukoencephalopathy syndrome. The clinical presentation usually includes seizures, headache, altered mental status, and blindness, often associated with hypertension and immunosuppressants. The authors discuss a two-year-old male with Down syndrome who presented 2 months after allogeneic bone marrow transplantation with severe oculogyric crisis, without other complaints. The patient was being treated for hypertension and was receiving cyclosporine for prophylaxis of graft-vs-host disease. A computed tomography scan of the head revealed marked bilateral lucencies mainly involving the white matter of the occipital lobes, with a few foci of punctate hemorrhage. The condition improved when cyclosporine was discontinued, but an area of leukomalacia was identified on follow-up magnetic resonance imaging. To the authors' knowledge, oculogyric crisis as a presentation of reversible posterior leukoencephalopathy has not been previously described. Recognizing this association is important, because patients receiving cyclosporine are often receiving other medications that can potentially cause dystonic eye movements, possibly leading to a delay in diagnosis and treatment, which can result in an irreversible neurologic deficit.

Asunto(s)

Encefalopatías/diagnóstico , Encefalopatías/etiología , Ciclosporina/efectos adversos , Hipertensión Maligna/complicaciones , Lóbulo Occipital/anomalías , Trastornos de la Motilidad Ocular/etiología , Trasplante de Médula Ósea , Preescolar , Cromosomas Humanos Par 7 , Progresión de la Enfermedad , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Imagen por Resonancia Magnética , Masculino , Monosomía , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/terapia , Lóbulo Occipital/patología , Síndrome , Tomografía Computarizada por Rayos X

RESUMEN

Unrelated bone marrow transplantation (BMT) is often complicated by fatal opportunistic infections. To evaluate features unique to immune reconstitution after unrelated BMT, the lymphoid phenotype, in vitro function, and life-threatening opportunistic infections after unrelated and related T-cell-depleted (TCD) BMT were analyzed longitudinally and compared. The effects of posttransplant donor leukocyte infusions to treat or prevent cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections on immune reconstitution were also analyzed. This study demonstrates that adult recipients of TCD unrelated BMTs experience prolonged and profound deficiencies of CD3(+), CD4(+), and CD8(+) T-cell populations when compared with pediatric recipients of unrelated BMT and adults after related BMT (P <.01), that these adults have a significantly increased risk of life-threatening opportunistic infections, and that the rate of recovery of CD4 T cells correlates with the risk of developing these infections. Recovery of normal numbers of CD3(+), CD8(+), and CD4(+) T-cell populations is similar in children after related or unrelated BMT. This study also demonstrates that adoptive immunotherapy with small numbers of unirradiated donor leukocytes can be associated with rapid restoration of CD3(+), CD4(+), and CD8(+) T-cell numbers, antigen-specific T-cell responses, and resolution of CMV- and EBV-associated disease after unrelated TCD BMT.

Asunto(s)

Envejecimiento , Trasplante de Médula Ósea , Transfusión de Leucocitos , Infecciones Oportunistas/inmunología , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Niño , Preescolar , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/prevención & control , Femenino , Humanos , Inmunoterapia Adoptiva , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/prevención & control