RESUMEN
Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8-24.5) post CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin ⩽6 g/dL and/or platelets <20 × 109/L). All AH patients were direct antiglobulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute GVHD. All 10 patients received rituximab 2-18 days after diagnosis, and corticosteroids combined with rituximab within <7 days was the most effective. No patient died of AH/ITP. AH/ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.
Asunto(s)
Anemia Hemolítica Autoinmune/etiología , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Neoplasias Hematológicas/complicaciones , Púrpura Trombocitopénica Idiopática/etiología , Rituximab/uso terapéutico , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Antineoplásicos Inmunológicos/uso terapéutico , Niño , Preescolar , Enfermedad Crítica , Estudios de Seguimiento , Neoplasias Hematológicas/terapia , Hemólisis , Humanos , Terapia de Inmunosupresión , Lactante , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto JovenRESUMEN
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 JovenRESUMEN
The feasibility of selecting cord blood (CB) units at high-resolution HLA match has not been investigated. We analyzed the high-resolution donor-recipient HLA match of 100 double-unit 4-6/6 HLA-A,-B antigen, -DRB1 allele-matched CB grafts (units 1a and 1b) and their back-up units (n=377 units in total). The median cryopreserved graft dose was 2.9 × 10(7)/kg/unit, and at high resolution these units had a median donor-recipient HLA-allele match of 5/8 (range 2-8/8) and 6/10 (range 2-9/10), respectively. We then evaluated how often use of high-resolution HLA-match criteria would change the original graft selection to substitute one or both of the back-up units for units 1a and/or 1b. On using a model in which both a higher eight-allele HLA match and a cell dose ⩾ 2.0 × 10(7)/kg/unit were required, graft selection changed in 33% of transplants with minimal effect on cell dose (8.3% reduction). In summary, while units chosen based on HLA-A,-B antigen and -DRB1 allele match have substantial mismatch at higher resolution, CB selection based on high-resolution HLA match is possible in a significant proportion of patients without compromise in cell dose.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Sangre Fetal/inmunología , Antígenos HLA-B/genética , Antígenos HLA-B/inmunología , Adolescente , Adulto , Anciano , Alelos , Niño , Preescolar , Femenino , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Adulto JovenRESUMEN
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 TratamientoAsunto(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 EmparentadoRESUMEN
Delayed or failed engraftment remains a concern after cord blood transplantation (CBT) even when using double-unit grafts. Therefore, we analyzed the association between BM assessment performed approximately 21 days after transplantation, and the speed and success of sustained donor-derived neutrophil engraftment in 56 myeloablative double-unit CBT (DCBT) recipients. Overall, the cumulative incidence of sustained neutrophil engraftment was 95% (95% confidence intervals (CI): 89-100). Of the percentage of myeloid precursors, the BM cellularity and the total donor chimerism the total donor chimerism percentage had the most critical association with the speed and success of engraftment. DCBT recipients who were 100% donor achieved a 98% engraftment rate at a median of 22 days. This compared with 100% engraftment in patients who were 90-99% donor, but at a delayed median of 29 days and only 68% engraftment in patients <90% donor at a median of 37 days (P=0.001). Multivariate analysis was performed in the subgroup of patients who had not engrafted at the time the BM analysis was performed, the subgroup of most clinical concern. This confirmed donor chimerism was predictive of subsequent neutrophil recovery (P=0.004). These findings demonstrate the importance of the day 21 BM chimerism determinations after DCBT.
Asunto(s)
Células de la Médula Ósea/citología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Supervivencia de Injerto , Neutrófilos/citología , Quimera por Trasplante , Adolescente , Adulto , Recuento de Células , Niño , Preescolar , Femenino , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Trasplante HomólogoRESUMEN
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 JovenRESUMEN
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 HomólogoRESUMEN
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/métodosRESUMEN
BACKGROUND: Diarrhea is a common complication of allogeneic bone marrow transplantation. Microbiologic stool studies are frequently ordered to rule out infectious etiology. The utility of examining multiple stool specimens per diarrheal episode has not been examined. METHODS: . We performed a retrospective review of 169 adult and pediatric patients who underwent hematopoietic stem cell transplantation at Memorial Sloan-Kettering Cancer Center from January 1, 2000 though December 31, 2001, who had at least 1 microbiologic stool study. We report on the incidence of enteric pathogens in our population and diagnostic yield of stool studies. A diarrheal episode was defined as a 14-day period from the date of the first stool study. Cost savings analysis was based on projected savings from implementation of proposed guidelines to the study population. RESULTS: A total of 1649 stool tests were performed (mean 10.6 tests per patient). An infectious cause of diarrhea was found in 45 (28.8%) patients. Diagnostic yield was 6.2% for Clostridum difficile toxin assay, 12.9% for viral cultures, and 1.3% for rotavirus enzyme immunoassay. Bacterial cultures for enteric pathogens, examination for parasites, and rotavirus antigen assay combined had 0.5% positive yield. CONCLUSIONS: Testing of multiple specimens per diarrheal episode did not increase diagnostic yield. The estimated cost savings by implementing single testing for each type of stool study per diarrheal episode was $49,764 annually (in 2001 US dollars). Judicious use of stool tests to evaluate diarrhea results in significant cost savings without compromising diagnostic yield.
Asunto(s)
Diarrea/diagnóstico , Heces , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Técnicas Microbiológicas/economía , Técnicas Microbiológicas/normas , Trasplante Homólogo/efectos adversos , Adulto , Niño , Preescolar , Análisis Costo-Beneficio , Diarrea/microbiología , Diarrea/parasitología , Diarrea/virología , Heces/microbiología , Heces/parasitología , Heces/virología , Humanos , Técnicas Microbiológicas/métodosRESUMEN
We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/terapia , Recurrencia Local de Neoplasia/prevención & control , Neuroblastoma/terapia , Adolescente , Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Preescolar , Terapia Combinada/métodos , Terapia Combinada/mortalidad , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/mortalidad , Neuroblastoma/mortalidad , Tiotepa/administración & dosificación , Tiotepa/efectos adversos , Topotecan/administración & dosificación , Topotecan/efectos adversos , Insuficiencia del TratamientoRESUMEN
Unrelated-donor marrow transplantation is a potential option for transplant candidates lacking a compatible related donor. The T-cell Depletion Study compared the 3-year disease-free survival for patients receiving T-cell-depleted (TCD) donor marrow (n = 203) vs unmanipulated donor marrow with methotrexate and cyclosporine (M/C) (n = 207). Hospital costs during index admission were documented with billing data, while hospital costs during subsequent 6-month follow-up were estimated from case report forms. Patients with index admission billing were included in the analysis (TCD = 119, M/C = 127). Total hospital length of stay (LOS) was similar across groups, with medians 47.0 days for TCD and 52.0 days for M/C (P = 0.72). Total hospital costs were comparable, 145,115 dollars vs 141,981 dollars (P = 0.63) for TCD and M/C, respectively. However, controlling for site and patient characteristics, TCD was associated with a 12.1% reduction in LOS for the index admission (95% CI -19.4%, -4.3%). Independent of treatment, HLA matching (6/6) was associated with an 8.6% (95% CI -17.4%, +1.2%) reduction in the index admission LOS, while cost was lower by 15.8% (95% CI -26.7%, -3.3%). Treatment costs were similar for TCD and M/C study groups. Savings on reduced cost for treating acute graft-versus-host disease were likely offset by increase in serious infections in the TCD arm.
Asunto(s)
Trasplante de Médula Ósea/economía , Depleción Linfocítica/economía , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Enfermedad Injerto contra Huésped/economía , Humanos , Lactante , Infecciones , Tiempo de Internación , Depleción Linfocítica/efectos adversos , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
BACKGROUND: Recent data indicate an exponential increase in proton pump inhibitor (PPI) prescribing, and concerns are raised regarding the appropriateness of these prescriptions and the financial implications. AIM: To survey the appropriateness of PPI prescription in a cohort of patients in a tertiary referral hospital. METHODS: Prescription records of all inpatients on a randomly selected day were reviewed. The appropriateness of prescription and relevant investigations were identified by interview of patients, review of patient records and of a computerised endoscopy records system. RESULTS: Thirty-two per cent (87 of 272) of all patients were on PPIs. A valid indication for therapy was not apparent in 63% of the patients on PPIs with the only predictive factor for inappropriate prescription being increasing age. Only 36 of the 87 patients on PPIs had undergone appropriate investigations for their gastrointestinal symptoms. Gender, age, speciality of admission or duration of hospital stay did not influence the appropriateness of prescription or performance of relevant investigations. CONCLUSION: There appears to be a widespread and inappropriate use of PPIs in hospital practice.
Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Revisión de la Utilización de Medicamentos , Inhibidores de la Bomba de Protones , Anciano , Prescripciones de Medicamentos/economía , Prescripciones de Medicamentos/normas , Endoscopía Gastrointestinal/estadística & datos numéricos , Inhibidores Enzimáticos , Femenino , Humanos , Entrevistas como Asunto , Irlanda , Masculino , Registros Médicos/estadística & datos numéricos , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Estudios RetrospectivosRESUMEN
The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and disease-free survival, acute and chronic graft-versus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Five-year overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P =.005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%; P <.0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-matched volunteer donors.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Trasplante de Médula Ósea/normas , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Grupos Raciales , Recurrencia , Sistema de Registros , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/normasRESUMEN
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 adversosRESUMEN
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 TratamientoRESUMEN
We analyzed engraftment of unrelated-donor (URD) bone marrow in 5246 patients who received transplants facilitated by the National Marrow Donor Program between August 1991 and June 1999. Among patients surviving at least 28 days, 4% had primary graft failure (failure to achieve an absolute neutrophil count > 5 x 10(8)/L before death or second stem-cell infusion). Multivariate logistic regression analysis showed that engraftment was associated with marrow matched at HLA-A, HLA-B, and DRB1; higher cell dose; younger recipient; male recipient; and recipient from a non-African American ethnic group. More rapid myeloid engraftment was associated with marrow serologically matched at HLA-A and HLA-B, DRB1 match, higher cell dose (in non-T-cell-depleted cases), younger recipient, recipient seronegativity for cytomegalovirus (CMV), male donor, no methotrexate for graft-versus-host disease prophylaxis, and transplantation done in more recent years. A platelet count higher than 50 x 10(9)/L was achieved by 47% of patients by day 100. Conditional on survival to day 100, survival at 3 years was 61% in those with platelet engraftment at day 30, 58% in those with engraftment between day 30 and day 100, and 33% in those without engraftment at day 100 (P <.0001). Factors favoring platelet engraftment were higher cell dose, DRB1 allele match, recipient seronegativity for CMV, HLA-A and HLA-B serologically matched donor, and male donor. Secondary graft failure occurred in 10% of patients achieving initial engraftment, and 18% of those patients are alive. These data demonstrate that quality of engraftment is an important predictor of survival after URD bone marrow transplantation.
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Trasplante de Médula Ósea/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Terapia Combinada , Comorbilidad , Infecciones por Citomegalovirus/epidemiología , Etnicidad , Femenino , Enfermedades Genéticas Congénitas/terapia , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Enfermedades Hematológicas/terapia , Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Lactante , Leucemia/terapia , Tablas de Vida , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias/terapia , Recuento de Plaquetas , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Factores de Tiempo , Acondicionamiento Pretrasplante , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: In the past, patients with metastatic retinoblastoma have had a poor prognosis when treated with conventional modalities. In the current study, the authors evaluated the use of combined intensive conventional chemotherapy, high dose chemotherapy with autologous stem cell rescue (ASCR), and radiation therapy. METHODS: Four patients with metastatic retinoblastoma were treated. All had orbital and bone marrow metastases. In addition, three patients had bone metastases and two patients had liver metastases. None had central nervous system disease. Patients received intensive conventional chemotherapy that included vincristine, cyclophosphamide, etoposide, and either cisplatin or carboplatin. Stem cells were harvested after bone marrow disease was no longer detectable. High dose chemotherapy with carboplatin (500 mg/m(2)/day x 3 days or area under the curve = 7 via the Calvert formula) and thiotepa (300 mg/m(2)/day x 3 days) with (n = 3 patients) or without (n = 1 patient) etoposide (250 mg/m(2)/day x 3 days) was administered with ASCR. Sites that originally harbored bulky disease were irradiated after recovery from the high dose chemotherapy. RESULTS: The therapy was associated with substantial acute hematopoietic and mucosal toxicities. At last follow-up, all four patients had survived event free from 46-80 months after the diagnosis of metastatic disease. CONCLUSIONS: The treatment strategy described in the current study is effective for patients with metastatic retinoblastoma that does not involve the central nervous system. However, a multicenter trial should be considered to evaluate it in a larger group of patients.
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Antineoplásicos/uso terapéutico , Neoplasias de la Médula Ósea/terapia , Trasplante de Células Madre Hematopoyéticas , Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Adolescente , Adulto , Antineoplásicos/efectos adversos , Neoplasias de la Médula Ósea/secundario , Terapia Combinada , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Neoplasias de la Retina/mortalidad , Neoplasias de la Retina/patología , Neoplasias de la Retina/radioterapia , Retinoblastoma/mortalidad , Retinoblastoma/radioterapia , Retinoblastoma/secundario , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Over a period of 8.5 years (February 1988 to October 1996), 1423 patients with chronic myelogenous leukemia (CML) underwent unrelated donor (URD) bone marrow transplants (BMTs) facilitated by the National Marrow Donor Program (NMDP) at 85 transplant centers. One hundred thirty-seven evaluable (9.9%) patients failed to engraft, and an additional 83 (6.6%) evaluable patients experienced late graft failure. Grade III/IV acute graft-versus-host disease (GVHD) developed in 33% of patients (95% confidence interval [CI], 30%-36%). The incidence of extensive chronic GVHD was 60% (95% CI, 56%-63%) at 2 years. Only 5.7% of patients (95% CI, 3.6%-7.8%) transplanted in chronic phase developed hematologic relapse at 3 years. Several factors were independently associated with improved disease-free survival (DFS), including transplant in chronic phase, transplant within 1 year of diagnosis, younger recipient age, a cytomegalovirus seronegative recipient, and development of no or mild acute GVHD. The combined effect of these factors on outcome is manifest in a subset (n = 157) of young (less than 35 years), chronic phase patients transplanted within 1 year of diagnosis using HLA-matched donors who had 63% (95% CI, 53%-73%) DFS at 3 years. URD BMT therapy for CML is both feasible and effective with more frequent and more rapid identification of suitable donors. Early URD transplant during chronic phase yields good results and should be considered in CML patients otherwise eligible for transplant but without a suitable related donor.