RESUMEN
Allogeneic hematopoietic stem cell transplant (AHSCT) outcomes data of older AML/myelodysplastic syndrome (MDS) patients are limited. We retrospectively evaluated consecutive patients ⩾60 years old with AML/MDS who underwent AHSCT between January 2005 and December 2014. The primary objectives were to determine nonrelapse mortality (NRM), relapse, relapse-free survival (RFS) and overall survival (OS) at 1 year post AHSCT. A total of 159 patients underwent AHSCT with a median age of 64 (range, 60-75) years. Of these, 103 patients (65%) had AML and 56 patients (35%) had MDS. At 1 year post AHSCT, grade III-IV acute GvHD and chronic GvHD occurred in 20.8% (95% confidence interval (CI), 14.9-27.5%) and 54.1% (95% CI, 46.0-61.5%) of patients, respectively. NRM, RFS, relapse rate and OS at 1 year post AHSCT were 25.3% (95% CI, 18.8-32.3%), 53.3% (95% CI, 46.1-61.7%), 21.4% (95% CI, 15.4-28.1%) and 56.4% (95% CI, 49.2-54.7%), respectively. High disease risk index was associated with poor RFS, OS and higher relapse rate (P<0.03), whereas non-thymoglobulin-based GvHD prophylaxis, higher comorbidity index (⩾3) and MDS were associated with higher NRM (P<0.03). Importantly, age did not have an adverse effect on NRM, relapse, RFS and OS. AHSCT was well tolerated. Hence, older age alone should not be considered a contraindication to AHSCT.
Asunto(s)
Factores de Edad , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Anciano , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Chronic GvHD (cGvHD) is the leading cause of late non-relapse mortality (NRM) and morbidity after allogeneic hematopoietic stem cell transplant (AHSCT). We analyzed the late effects of a phase II trial testing the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymoglobulin Thymo) in combination with tacrolimus and sirolimus (TTS) in 47 patients (pts) for the prevention of acute and chronic GvHD after unrelated AHSCT. The median follow-up was 45.2 months. The cumulative incidence of NIH severe cGvHD at 48 months was 6.4% with no new occurrences past 6 months for the entire follow-up period. The overall cumulative incidence of cGvHD was 44.7%. Out of 20 pts who are alive and disease-free at the last follow-up, only 4 pts continue to need systemic immune suppression. We observed low late NRM with only 3 transplant-related deaths after 6 months post transplant. At 4 years of follow-up, the overall cumulative incidence of NRM and disease relapse was 27.7% and 30.0%, respectively. PFS and overall survival (OS) at 4 years were 42 and 47%. At long term follow-up, TTS was associated with low incidence of severe cGvHD and late NRM.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Sirolimus/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Anciano , Suero Antilinfocítico/farmacología , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Inmunosupresores/farmacología , Incidencia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Sirolimus/farmacología , Tasa de Supervivencia , Tacrolimus/farmacología , Adulto JovenRESUMEN
The use of hematopoietic cell transplantation (HCT) has risen in recent years and additional increases are projected in the near- and long-term future. The complex nature of HCT, along with its potentially rigorous follow-up care requirements, presents numerous potential barriers to accessing this important service (for example, financial considerations, donor availability and sociodemographic factors). The distance between a patient and an HCT facility also appears to be an important factor in both HCT use and outcomes. We provide the first comprehensive and detailed evaluation of geographic access to HCT services for the adult (18+ years) and pediatric (0-17 years) populations in the United States. Population-level access is examined as well as detailed gender, race/ethnicity and age breakdowns. Generally, access to HCT services appears to be quite high throughout the United States, as 48%, 78.6% and 94.7% of the 18+ years age population has 30, 90 and 180 min access (respectively) to an adult HCT facility and 42.5%, 72% and 91.5% of the 0-17 years age population has 30, 90 and 180 min access (respectively) to a pediatric facility.
Asunto(s)
Accesibilidad a los Servicios de Salud , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Accesibilidad a los Servicios de Salud/economía , Accesibilidad a los Servicios de Salud/organización & administración , Accesibilidad a los Servicios de Salud/tendencias , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/tendencias , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Estados UnidosRESUMEN
Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos/patología , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Recurrencia , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Trasplante HomólogoRESUMEN
We performed a retrospective analysis of the outcome of 197 consecutive unrelated donor transplant recipients who received GVHD prophylaxis either TM regimen (tacrolimus and mycophenolate) (121 patients) or TM/ATG-G regimen (TM with low-dose antithymocyte globulin (ATG) of 4.5 mg/kg, ATG-G, Genzyme) (76 patients). Cumulative incidences of grade II-IV acute GVHD for the TM and TM/ATG-G cohorts were 49% and 61% (P=0.11) and grade III-IV acute GVHD for the TM and TM/ATG-G cohorts were 27% and 14% (P=0.02), respectively. There was no difference in the incidence of relapse or disease progression between TM and TM/ATG-G-16% and 23% (P=0.64). TM/ATG-G cohort had lower incidence of non-relapse mortality (NRM; 37% vs 20%, P=0.01), chronic GVHD (56% vs 43%, P<0.001) and more favorable global chronic GVHD severity (P<0.001). Univariate analyses showed improved OS and PFS of patients who received TM/ATG-G. Multivariate analysis confirmed TM/ATG-G had a favorable influence on OS (P=0.05) but not on PFS (P=0.07). We concluded that low-dose ATG of 4.5 mg/kg given in conjunction with TM improved GVHD prophylaxis without increased risk of relapse. Lower NRM, lower incidence and severity of chronic GVHD could potentially improve survival.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Enfermedad Injerto contra Huésped , Inmunosupresores/administración & dosificación , Ácido Micofenólico/análogos & derivados , Trasplante de Células Madre , Tacrolimus/administración & dosificación , Adulto , Anciano , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Factores de Riesgo , Donante no EmparentadoRESUMEN
We report the long-term follow up of 49 patients (pts) enrolled on plerixafor compassionate use protocol. Thirty-seven pts (76%) had failed one previous mobilization attempt, while 12 (24%) had failed two or more previous attempts. Using the combination of plerixafor and granulocyte colony-stimulating factor, we collectedî¶2.5 × 10(6) CD34+cells/kg in 33 pts (67%). Forty-three of the 49 pts proceeded to an auto-SCT (ASCT). The median days to WBC and platelet engraftment were 11 (range, 9-13 days) and 16 (range, 11-77 days) days post ASCT, respectively. The median WBC count, Hb and platelet counts 1 year after ASCT were 4.7 × 10(9)/L, 12.2 g/dL and 109 × 10(9)/L, respectively. With median follow up of 42 months (range <1-54 months), 21 pts had evidence of disease progression. Five pts developed myelodysplastic syndrome (MDS)/AML at median of 29 months post ASCT. The cumulative incidence of MDS/AML at 42 months was 17% (95% confidence interval, 6 to 32%). Development of secondary MDS/AML in pts proceeding to ASCT after plerixafor mobilization needs to be studied further in a larger cohort.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Leucemia Mieloide Aguda/etiología , Síndromes Mielodisplásicos/etiología , Neoplasias Primarias Secundarias/etiología , Adulto , Anciano , Bencilaminas , Ensayos de Uso Compasivo , Ciclamas , Femenino , Estudios de Seguimiento , Movilización de Célula Madre Hematopoyética/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Incidencia , Leucemia Mieloide Aguda/inmunología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/inmunología , Neoplasias Primarias Secundarias/inmunología , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenAsunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/uso terapéutico , Leucopenia/sangre , Trombocitopenia/sangre , Bencilaminas , Eliminación de Componentes Sanguíneos/métodos , Ciclamas , Trasplante de Células Madre Hematopoyéticas , Humanos , Recuento de Leucocitos , Leucopenia/patología , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/cirugía , Mieloma Múltiple/sangre , Mieloma Múltiple/cirugía , Recuento de Plaquetas , Estudios Retrospectivos , Trombocitopenia/patologíaRESUMEN
Before US regulatory approval, an expanded access program provided plerixafor to patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma (MM) who had not previously failed mobilization and were otherwise candidates for auto-SCT. Patients received granulocyte-CSF (G-CSF) 10 mcg/kg daily and plerixafor 0.24 mg/kg starting on day 4 with apheresis on day 5; all repeated daily until collection was complete. Overall, 104 patients received î¶1 dose of plerixafor. The addition of plerixafor to G-CSF resulted in a median threefold increase in peripheral blood CD34+ cell count between days 4 and 5. Among 43 NHL patients, 74% met the target of î¶5 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-5 days); among 7 HD patients, 57% met the target of î¶5 × 10(6) CD34+ cells/kg (median, 2 days apheresis, range 1-3); and among 54 MM patients, 89% met the target of î¶6 × 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-4). Overall, 93% of patients had î¶2 × 10(6) CD34+ cells/kg collected within 1-3 days. Plerixafor-related toxicities were minimal. Engraftment kinetics, graft durability and transplant outcomes demonstrated no unexpected outcomes. Efficacy and safety results were similar to results in phase II and III clinical trials.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Compuestos Heterocíclicos/administración & dosificación , Enfermedad de Hodgkin/terapia , Linfoma no Hodgkin/terapia , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Bencilaminas , Eliminación de Componentes Sanguíneos , Ciclamas , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Compuestos Heterocíclicos/efectos adversos , Enfermedad de Hodgkin/sangre , Humanos , Linfoma no Hodgkin/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Estados UnidosRESUMEN
We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16 mg/kg/day, with a subsequent dose increase in one case to 0.24 mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24 mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24 mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Compuestos Heterocíclicos/administración & dosificación , Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica , Insuficiencia Renal/terapia , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Bencilaminas , Eliminación de Componentes Sanguíneos , Ciclamas , Relación Dosis-Respuesta a Droga , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Movilización de Célula Madre Hematopoyética/efectos adversos , Compuestos Heterocíclicos/efectos adversos , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Diálisis Renal , Insuficiencia Renal/complicaciones , Trasplante Autólogo , Trasplante HomólogoRESUMEN
We retrospectively compared clinical outcomes in 1593 T-replete unrelated donor (URD) marrow transplant recipients with AML, MDS and CML who received myeloablative conditioning regimens of either BU and CY (BuCy), standard-dose Cy/TBI (1000-1260 cGy) or high-dose Cy/TBI (1320-1500 cGy). Subjects were drawn from patients transplanted between 1991 and 1999 facilitated by the National Marrow Donor Program. Patients who received high-dose Cy/TBI regimens were slightly younger, more likely to receive a mismatched transplant and to have intermediate or advanced disease compared with patients in the BuCy or standard-dose TBI group. Neutrophil recovery was significantly higher in the standard-dose CY/TBI group compared with the high-dose Cy/TBI or BuCy group. Patients who received the high-dose Cy/TBI regimen had an increased risk of developing grades III-IV aGVHD when compared with the control group who received BuCy (P = 0.011). OS, disease-free survival (DFS), TRM and relapse were not significantly different between any of the regimens. We conclude that BuCy, standard-dose and high-dose Cy/TBI regimens have equivalent efficacy profiles for OS, DFS, TRM and relapse risk in patients undergoing T-replete URD marrow transplantation for AML, CML and MDS.
Asunto(s)
Trasplante de Médula Ósea , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Leucemia Mieloide/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Preescolar , Terapia Combinada/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide de Fase Crónica/terapia , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Resultado del Tratamiento , Irradiación Corporal Total/efectos adversos , Adulto JovenRESUMEN
Large pericardial effusion (LPE) leading to cardiac tamponade is a rare complication described in patients undergoing SCT. This complication is considered to be a manifestation of chronic GVHD; however its pathophysiology is poorly understood. Currently, there are no published data systematically describing the incidence, clinical characteristics and outcomes of LPEs in adult stem cell transplant recipients. We retrospectively evaluated 858 adult patients (512 autologous, 148 related and 198 unrelated donor) who underwent hematopoietic stem cell and BM transplants at our institution from 2005 to 2008 for the development of post transplant LPE. Seven patients (0.8%) were found to have LPEs and all these patients had undergone unrelated allografts. The median day of diagnosis post transplant was 229 (range 42-525). None of these patients had active manifestations of GVHD other than serositis at the time of LPE detection. Pericardial window (PW) was successfully placed in all patients who developed cardiac tamponade and most patients with LPE were effectively treated by increasing immunosuppression. We conclude that LPE is a rare late complication after allogeneic transplant in adults and in our study developed only after unrelated transplant. PW can be safely performed in these patients and LPEs can be successfully treated with intensification of systemic immunosupression.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Derrame Pericárdico/etiología , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pericárdico/diagnóstico , Estudios RetrospectivosAsunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/inmunología , Adulto , Enfermedad Crónica , Humanos , Masculino , Persona de Mediana Edad , RituximabRESUMEN
The aim of the present article is to review the available clinical data on bronchiolitis obliterans following haematopoietic stem cell transplantation (HSCT). The data sources used were the Medline database and references from the identified articles related to bronchiolitis obliterans, noninfectious pulmonary complications and HSCT. HSCT is an important treatment for a variety of malignant and nonmalignant conditions. However, the procedure is limited by significant complications that may involve every organ of the body. Pulmonary complications are seen in 40-60% of HSCT recipients. The recent advances in prophylaxis and treatment of infectious complications have increased the significance of late noninfectious pulmonary conditions. Currently, bronchiolitis obliterans is one of the most challenging pulmonary complications facing clinicians who are taking care of haematopoietic stem cell transplantation recipients. This article reviews the clinical and pathological features of this condition, sheds some light on potential mechanisms of pathogenesis, and discusses the available management options.
Asunto(s)
Bronquiolitis Obliterante/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/terapia , Broncoscopía , Humanos , Trasplante de Pulmón , Pronóstico , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
Chronic graft-versus-host disease (cGVHD) is the most common late complication of allogeneic hematopoietic cell transplantation (HCT) causing significant morbidity and mortality. The kidneys are not considered a target organ for cGVHD in humans, although animal models show renal damage. Renal involvement in patients with cGVHD, presenting as nephrotic syndrome (NS), has rarely been reported in patients who received allogeneic transplantation. Herein we describe, by far, the largest series of nine patients with NS associated with cGVHD, including two patients who received a reduced-intensity regimen. Pathological features of membranous nephropathy were the most common finding on renal biopsy. The clinical course of the NS was temporally associated with the classical features of cGVHD in all but one of the nine cases. The clinicopathologic features of NS in our series as well as reports in the literature demonstrate an immunopathologic process typical of antibody-mediated damage consistent with cGVHD. Treatment directed against antibody-mediated damage, such as anti-B-cell antibody may play an important role in ameliorating NS associated with cGVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Nefrótico/etiología , Adulto , Biopsia , Enfermedad Crónica , Femenino , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Síndrome Nefrótico/patología , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Multiple diverse biomedical variables have been shown to affect outcome after hematopoietic stem cell transplantation (HSCT). Whether psychosocial variables should be added to the list is controversial. Some empirical reports have fueled skepticism about the relationship between behavioral variables and HSCT survival. Most of these reports have methodological shortcomings. Their samples were small in size and included heterogeneous patient populations with different malignant disease and disease stages. Most data analyses did not control adequately for biomedical factors using multivariate analyses. The pre-transplant evaluations differed from study to study, making cross-study generalizations difficult. Nevertheless, a few recently published studies challenge this skepticism, and provide evidence for deleterious effects of depressive symptomatology on HSCT outcome. This mini review integrates the new data with previously reviewed data, focusing on the differential impact of negative and positive emotional profiles on survival. Pre-transplant negative emotional profiles are associated with worse survival in the long term, whereas pre-transplant optimism about transplant appears to affect survival in the short term. These data have practical implications for transplant teams. Pre-transplant psychological evaluation should assess for specific adverse behavioral risk factors, particularly higher levels of depression and lower levels of optimistic expectations about transplant. Transplant centers should develop collaborative studies to further test the effects of these adverse behavioral risk factors, and run multicenter hypothesis-driven clinical trials of psychological intervention protocols. Such studies should aim to better define pragmatics of assessment and intervention (timing, assessment tools, personnel), and evaluate their contribution to improving outcome after transplant.
Asunto(s)
Emociones , Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/psicología , Adulto , Síntomas Conductuales/diagnóstico , Humanos , Resultado del TratamientoRESUMEN
We report long-term outcomes for allogeneic peripheral blood stem cell (PBSC) recipients, evaluating cumulative incidence (CI) of acute and chronic graft-versus-host disease (GVHD), after use of tacrolimus with or without minidose methotrexate for GVHD prophylaxis. From April 1996 to April 1998, 97 adults underwent allogeneic PBSC transplantation. The first 49 received tacrolimus monotherapy as GVHD prophylaxis and the subsequent 48 received combination therapy. The median follow-up for survivors was 67 months. Compared to combination therapy, tacrolimus monotherapy resulted in enhanced neutrophil engraftment, shortened hospitalization, comparable rates of GVHD, and equivalent 100-day survival. The CI of grades II-IV acute GVHD was 35% with tacrolimus and 23% with the combination (P=0.19). The CI of III-IV GVHD was 22% for tacrolimus and 19% for the combination. CI of chronic GVHD was similar between the two groups (P=0.5). Patients with good-risk disease had superior overall survival (OS) when compared to those with poor-risk features (P<0.001). Within the good-risk disease category, patients receiving methotrexate had a trend towards improved OS (P=0.07). Multivariate analysis indicated good-risk disease status and methotrexate were independently associated with improved OS, progression-free survival (PFS), and relapse. In addition, patients developing chronic GVHD had a significantly reduced risk of relapse and improved PFS.
Asunto(s)
Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/administración & dosificación , Metotrexato/administración & dosificación , Tacrolimus/administración & dosificación , Enfermedad Aguda , Adulto , Enfermedad Crónica , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/mortalidad , Hospitalización , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Prevención Secundaria , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.
Asunto(s)
Enfermedades del Sistema Nervioso Central/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fiebre del Nilo Occidental/complicaciones , Autopsia , Resultado Fatal , Humanos , Masculino , Mesencéfalo/patología , Mesencéfalo/virología , Microscopía Electrónica , Persona de Mediana EdadRESUMEN
High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.
Asunto(s)
Adenoviridae/genética , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/terapia , Trasplante de Células Madre Hematopoyéticas , Proteínas Proto-Oncogénicas c-bcl-2/genética , Acondicionamiento Pretrasplante , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Protocolos Clínicos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Vectores Genéticos , Humanos , Proteína bcl-XRESUMEN
Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in long-term survivors of allogeneic stem cell transplantation. The immunopathogenesis of chronic GVHD is, in part, TH-2 mediated, resulting in a syndrome of immunodeficiency and an autoimmune disorder. The most important risk factor for chronic GVHD is prior history of acute GVHD and strategies that prevent acute GVHD also decrease the risk of chronic GVHD. Other important risk factors are the use of a non-T cell-depleted graft, and older age of donor and recipient. Whether recipients of peripheral blood stem cells are at increased risk of chronic GVHD remains unsettled. There are no known pharmacologic agents which can specifically prevent development of chronic GVHD. Agents which have efficacy in the treatment of autoimmune disorders have been utilized as therapy for established chronic GVHD and are associated with response rates of 20% to 80%. Most responses are confined to skin, soft tissue, oral mucosa and occasionally liver. Bronchiolitis obliterans responds infrequently to therapy and is associated with a dismal prognosis. Newer, promising therapeutic strategies under investigation include thalidomide, photopheresis therapy, anti-tumor necrosis factor and B cell depletion with anti-CD20 monoclonal antibody.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas , Animales , Enfermedad Crónica , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Trasplante Homólogo/inmunologíaRESUMEN
The incidence of anaerobic bloodstream infections (BSI) in patients who underwent bone marrow transplantation (BMT) recently increased at our institution. A retrospective case-control study of patients undergoing BMT from January 1995 through December 1998 was performed to determine the microbiological characteristics, epidemiology, and outcome of anaerobic BSI and to identify independent risk factors for infection. Anaerobic BSI occurred in 23 patients, for a rate of 4 BSIs per 100 BMT procedures, and it accounted for 17% of all BSIs that occurred during the study period. Infection occurred at a mean (+/- standard deviation) of 7+/-4 days after BMT and 7+/-5 days after the onset of neutropenia. Fusobacterium nucleatum was the most frequently isolated pathogen (in 17 patients), followed by Leptotrichia buccalis (in 4), Clostridium septicum (in 1), and Clostridium tertium (in 1). Two case patients (9%) died. Severity of mucositis was an independent predictor of anaerobic BSI (odds ratio, 4.4; P=.01). Controlling mucositis is critical for the prevention of anaerobic BSI in this patient population.