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1.
Transpl Infect Dis ; 14(5): 468-78, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22548788

RESUMEN

Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen-identical related-donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow-up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment-related mortality, survival, graft-versus-host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Hepatitis B/mortalidad , Hepatitis C/mortalidad , Trasplante Homólogo/mortalidad , Adolescente , Adulto , Niño , Preescolar , Femenino , Hepacivirus , Hepatitis B/epidemiología , Hepatitis B/virología , Virus de la Hepatitis B , Hepatitis C/epidemiología , Hepatitis C/virología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Trasplante , Adulto Joven
2.
Bone Marrow Transplant ; 41(8): 709-14, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18195688

RESUMEN

Achievement of complete donor chimerism (CDC) after allogeneic nonmyeloablative hematopoietic stem cell transplantation (NMHSCT) is important for preventing graft rejection and for generating a graft-vs-malignancy effect. The alloreactivity of NK cells and some T-cell subsets is mediated through the interaction of their killer immunoglobulin-like receptors (KIRs) with target cell HLA/KIR ligands. The influence of KIR matching on the achievement of T-cell CDC after NMHSCT has not been previously described. We analyzed 31 patients undergoing T-cell replete related donor NMHSCT following fludarabine and 200 cGy TBI. Recipient inhibitory KIR genotype and donor HLA/KIR ligand matches were used to generate an inhibitory KIR score from 1 to 4 based upon the potential number of recipient inhibitory KIRs that could be engaged with donor HLA/KIR ligands. Patients with a score of 1 were less likely to achieve T-cell CDC (P=0.016) and more likely to develop graft rejection (P=0.011) than those with scores greater than 1. Thus, patients with lower inhibitory KIR scores may have more active anti-donor immune effector cells that may reduce donor chimerism. Conversely, patients with greater inhibitory KIR scores may have less active NK cell and T-cell populations, which may make them more likely to achieve CDC.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Receptores KIR/genética , Quimera por Trasplante/inmunología , Acondicionamiento Pretrasplante/métodos , Adulto , Quimerismo , Estudios de Cohortes , Femenino , Genotipo , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Receptores KIR/inmunología , Linfocitos T/trasplante , Quimera por Trasplante/genética
3.
Bone Marrow Transplant ; 41(7): 635-42, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18084335

RESUMEN

For adults with high-risk or recurrent ALL who lack a suitable sibling donor, the decision between autologous (Auto) and unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) is difficult due to variable risks of relapse and treatment-related mortality (TRM). We analysed data from two transplant registries to determine outcomes between Auto and URD HSCT for 260 adult ALL patients in first (CR1) or second (CR2) CR. All patients received a myeloablative conditioning regimen. The median follow-up was 77 (range 12-170) months. TRM at 1 year post transplant was significantly higher with URD HSCT; however, there were minimal differences in TRM according to disease status. Relapse was higher with Auto HSCT and was increased in patients transplanted in CR2. Five-year leukemia-free (37 vs 39%) and overall survival (OS) rates (38 vs 39%) were similar for Auto HSCT vs URD HSCT in CR1. There were trends favoring URD HSCT in CR2. The long-term follow-up in this analysis demonstrated that either Auto or URD HSCT could result in long-term leukaemia-free survival and OS for adult ALL patients. The optimal time (CR1 vs CR2) and technique to perform HSCT remains an important clinical question for adult ALL patients.


Asunto(s)
Trasplante de Médula Ósea/métodos , Recurrencia Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Adolescente , Adulto , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento
4.
Bone Marrow Transplant ; 41(6): 537-45, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18084340

RESUMEN

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.


Asunto(s)
Neoplasias de la Mama/terapia , Trasplante de Células Madre Hematopoyéticas , Adulto , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Efecto Injerto vs Tumor , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Metástasis de la Neoplasia , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo
5.
Bone Marrow Transplant ; 40(5): 437-41, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17618321

RESUMEN

The cellular composition of an autologous graft may influence autologous stem cell transplantation (ASCT) outcome. Etoposide (VP) plus filgrastim (G) frequently mobilizes high numbers of CD34+ cells for autologous transplantation. We investigated whether patients collecting high numbers of CD34+ cells ('super mobilizers') have a better outcome than other patients. We reviewed 350 consecutive adult patients with NHL or Hodgkin's lymphoma receiving an ASCT from January 1994 to December 2005, mobilized with VP+G. Super mobilizers were defined as collecting a minimum of 8 x 10(6) CD34+ cells/kg. Two hundred and three patients were super mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Super mobilizers were younger and more likely to have received two or fewer prior chemotherapy regimens (80 versus 63%, P<0.001). Median CD34+ cell dose for the super mobilizing group was 13.7 x 10(6) versus 4.4 x 10(6)/kg in the standard collecting group. The super mobilizer group had a superior overall survival (P=0.006). In multivariable analysis, favorable disease status and younger age at transplant, and super mobilization were associated with improved survival. We conclude that patients had an improved ASCT outcome if large numbers of CD34+ cells were mobilized and infused. The explanation for this observation is unknown.


Asunto(s)
Antígenos CD34 , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/normas , Células Madre Hematopoyéticas/citología , Linfoma/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Recolección de Datos , Humanos , Recuento de Leucocitos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
6.
Bone Marrow Transplant ; 39(7): 417-24, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17310134

RESUMEN

The reactivity of natural killer cells and some T-cell populations is regulated by killer immunoglobulin-like receptors (KIR) interactions with target cell HLA class I molecules. Such interactions have been suggested to influence outcomes after allogeneic hematopoietic stem cell transplantation, particularly for myeloid malignancies and with T-cell depletion. Donor KIR genotypes and recipient HLA KIR ligands were analyzed in 60 AML patients receiving T-cell replete, HLA-matched-related donor allogeneic bone marrow transplants. Patients were categorized according to their HLA inhibitory KIR ligand groups by determining whether or not they expressed: HLA-A3 or -A11; HLA-Bw4 and HLA-Cw groups (homozygous C1, homozygous C2 or heterozygous C1/C2). Heterozygous C1/C2 patients had significantly worse survival than those homozygous for C1 or C2 (5.8 vs 43.5 months, respectively, P=0.018) and the C1/C2 group had a higher relapse rate (47 vs 31%, respectively, P=0.048). Multivariate analysis found C1/C2 status to be an independent predictor for mortality (P=0.007, HR 2.54, confidence interval 1.29-5.00). C1/C2 heterozygosity was also associated with a delayed time to platelet engraftment, particularly for those with concurrent HLA-Bw4 expression (P=0.003). Since C1/C2 heterozygotes have a greater opportunity to engage inhibitory KIRs than do C1 or C2 homozygotes, they may more effectively inhibit KIR-positive NK- and T-cell populations involved in graft vs leukemia responses.


Asunto(s)
Trasplante de Médula Ósea/métodos , Antígenos HLA-C/biosíntesis , Prueba de Histocompatibilidad , Células Asesinas Naturales/inmunología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Trasplante Homólogo/métodos , Adolescente , Adulto , Niño , Femenino , Efecto Injerto vs Leucemia , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
7.
Bone Marrow Transplant ; 40(3): 239-43, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17530000

RESUMEN

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T/mortalidad , Linfoma de Células T/terapia , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma de Células B/mortalidad , Linfoma de Células B/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo
8.
Bone Marrow Transplant ; 40(10): 973-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17873917

RESUMEN

Autologous stem-cell transplantation (ASCT) has been used in follicular lymphoma (FL) to achieve durable responses in first remission or in the relapsed or refractory settings. Addition of rituximab to chemotherapy for FL has been shown to improve survival. The impact of prior therapy with rituximab upon the effectiveness of high-dose therapy (HDT) and ASCT in patients with FL is unknown. We retrospectively reviewed consecutive patients with FL who underwent HDT and ASCT. Patients were categorized according to prior therapy with rituximab. Outcomes were compared between groups in all patients and in a well-matched subset. In all 35 patients received prior rituximab and 71 rituximab-naive patients were analyzed. The rituximab-naive group had a median overall survival (OS) that was not reached during follow-up, with a median relapse-free (RFS) survival of 49.9 months. The prior rituximab group also did not reach median OS and had a median RFS of 24.6 months. Survivals were not significantly different in this group or in the well-matched subset. In conclusion, these results suggest that the use of rituximab-based regimens for the treatment of FL does not compromise the effectiveness of HDT and ASCT as a salvage strategy in patients with FL.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfoma Folicular/terapia , Trasplante de Células Madre de Sangre Periférica , Adulto , Anticuerpos Monoclonales de Origen Murino , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rituximab , Trasplante Autólogo
9.
Bone Marrow Transplant ; 37(2): 223-8, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16273113

RESUMEN

BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.


Asunto(s)
Trasplante de Médula Ósea/psicología , Toma de Decisiones , Relaciones Médico-Paciente , Médicos/psicología , Encuestas y Cuestionarios , Determinación de la Elegibilidad , Humanos , Trasplante Homólogo
10.
Bone Marrow Transplant ; 51(9): 1191-6, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27111046

RESUMEN

Socioeconomic status (SES) is an important determinant of disparities in health care. The association of SES with outcomes in autologous hematopoietic cell transplantation (AHCT) has not been described previously. We conducted a retrospective cohort study of 687 AHCT recipients with lymphoma transplanted between 2003 and 2013. Patients were categorized into low (<$50 000/year) and high SES (⩾$50 000/year). A greater proportion of low SES patients lived farther away from our center (median 54 vs 28 miles), belonged to a racial minority (12 vs 3%), had poorer performance status (4 vs 1%) and had high-risk disease at AHCT (9 vs 5%). Median follow-up was 53 months. In univariable analysis, low SES patients had significantly higher relapse mortality and lower OS and PFS. This was confirmed on multivariable analysis for relapse mortality (HR for high vs low SES: 0.74 (95% confidence interval (CI), 0.54-0.99), P=0.05), OS (HR 0.74 (0.58-0.95), P=0.02) and PFS (HR 0.77 (0.63-0.95), P=0.02). In multivariable analysis of ⩾1-year progression-free survivors, high SES patients had better OS (HR 0.73, P=0.05 vs low SES) that was primarily driven by a trend toward lower risk of non-relapse mortality (HR 0.62, P=0.06). SES is associated with outcomes of AHCT in patients with lymphoma.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Linfoma/terapia , Clase Social , Adulto , Anciano , Femenino , Humanos , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
11.
J Clin Oncol ; 19(2): 406-13, 2001 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-11208832

RESUMEN

PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Anciano , Niño , Terapia Combinada , Femenino , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasia Residual , Modelos de Riesgos Proporcionales , Inducción de Remisión , Análisis de Supervivencia , Trasplante Autólogo
12.
Bone Marrow Transplant ; 36(12): 1049-52, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16247431

RESUMEN

Allograft dendritic cell (DC) content has been identified as a predictor of relapse and event-free survival after allogeneic bone marrow transplantation. However, the prognostic importance of DCs has not been evaluated in the setting of autologous hematopoietic stem cell transplantation (HSCT). We prospectively determined pre-transplant and post transplant DC levels, including DC1 and DC2 subset levels, in 53 patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBC NHL) undergoing autologous HSCT. Pre-transplant DCs were measured in the collected stem cell products and were therefore indicative of cell numbers infused directly into patients; post transplant analysis of DCs was performed on the peripheral blood of patients 6 weeks after the infusion of autologous stem cells. Higher pre-transplant levels of DC1 cells and total DCs were significantly associated with improved survival. Similarly, greater post transplant levels of total DCs and both subsets were significantly associated with survival. These findings suggest a relationship between DC reconstitution and survival following autologous HSCT for DLBC NHL. Strategies to increase autograft DC content or accelerate DC recovery after autologous HSCT might improve outcomes in this setting.


Asunto(s)
Células Dendríticas/citología , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B/mortalidad , Linfoma de Células B/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Células de la Médula Ósea/citología , Trasplante de Médula Ósea , Proliferación Celular , Trasplante de Células , Femenino , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/metabolismo , Movilización de Célula Madre Hematopoyética , Humanos , Linfoma , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Pronóstico , Estudios Prospectivos , Recurrencia , Trasplante de Células Madre , Células Madre/citología , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento
13.
Bone Marrow Transplant ; 35(7): 653-61, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15711571

RESUMEN

SUMMARY: To reduce relapse following allogeneic transplantation for AML, intensification of high-dose busulfan/cyclophosphamide using additional agents has been investigated but with few reported comparisons. We compared an intensified regimen of etoposide (60 mg/kg), busulphan (14 mg/kg), and cyclophosphamide (120 mg/kg) (BuCyVP) with BuCy2 in 237 AML patients. No significant difference in overall outcome was observed following BuCyVP (n=127) or BuCy2 (n=110). The 5-year survival was 27.3 and 30.1% following BuCyVP and BuCy2, respectively (P=0.48). Similarly, the 5-year cumulative incidence of relapse (CIR) was 28.3 and 34.8% with BuCyVP and BuCy2 (P=0.45), respectively. On multivariable analysis, patients transplanted in CR1 (P=0.002) and from related donors (P=0.013) had longer survival, while disease status at transplant was the only factor predicting CIR (P=0.002). In a separate analysis of CR1 patients (n=56), there was no significant difference in survival (P=0.37) or CIR (P=0.87) between the two regimens. However, for more advanced disease, there was a trend towards less relapse with BuCyVP (P=0.08), which was balanced by a higher cumulative incidence of transplant-related deaths (P=0.03) compared to BuCy2, resulting in similar survival. Overall, our results do not support the use of the more intensive BuCyVP regimen over BuCy2 in either early or more advanced disease AML patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide/terapia , Enfermedad Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Busulfano/administración & dosificación , Causas de Muerte , Ciclofosfamida/administración & dosificación , Etopósido/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped , Humanos , Leucemia Mieloide/complicaciones , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento
14.
Leukemia ; 2(5): 253-60, 1988 May.
Artículo en Inglés | MEDLINE | ID: mdl-3287015

RESUMEN

High dose cytarabine (HDARAC) therapy is used increasingly to treat hematologic malignancies. Recent data indicate that HDARAC at doses of 2-3 g/M2 every 12 hr x 10-12 doses is of comparable or greater efficacy in remission induction as standard doses of cytarabine in acute myelogenous leukemia. HDARAC can also produce remissions in individuals resistant to conventional doses. HDARAC-containing regimens are reported to result in substantially higher long-term, disease-free survival than previous approaches to post-remission therapy, but this has not yet been confirmed in controlled trials. HDARAC is also active in acute lymphocytic leukemia. Because intravenous HDARAC achieves high levels in the spinal fluid, it is useful to treat central nervous system leukemia and may provide adequate CNS prophylaxis in acute lymphocytic leukemia. HDARAC is reported to be active in advanced non-Hodgkin lymphomas and chronic myelogenous leukemia in acute phase; optimal use in these settings is under study. HDARAC has also been combined with other drugs. Randomized trials are needed to determine whether these combinations are more effective than HDARAC alone. Apart from potent myelosuppression, the dose-limiting toxicity of HDARAC is cerebellar damage. This occurs with increased frequency in patients greater than 50 years old. HDARAC is active in hematologic malignancies and may further improve therapeutic results if combined with other drugs.


Asunto(s)
Citarabina/administración & dosificación , Leucemia Linfoide/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Amsacrina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/uso terapéutico , Citarabina/efectos adversos , Citarabina/uso terapéutico , Daunorrubicina/administración & dosificación , Humanos , Leucemia Mieloide/tratamiento farmacológico , Pancitopenia/inducido químicamente
15.
Leukemia ; 1(8): 575-9, 1987 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3312846

RESUMEN

We analyzed clinical trials of low dose cytosine arabinoside (LDARA-C) in 324 patients with acute myelogenous leukemia (AML) and 129 patients with myelodysplasia (MDS). Complete and partial remission rates were 31% and 18%, respectively, in patients with AML, and 24% and 27% in patients with MDS. Toxicity was primarily hematologic. Although in vitro data suggested that LDARA-C acts as a differentiating agent, clinical data generally indicate a cytotoxic mechanism. Given the lack of effective therapeutic options in MDS and high risk AML (patients greater than 65 years old, secondary AML), these data are encouraging. LDARA-C warrants further study, comparing continuous infusion with intermittent subcutaneous administration and comparing LDARA-C to conventional dose therapy.


Asunto(s)
Citarabina/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Factores de Edad , Citarabina/efectos adversos , Humanos
16.
Exp Hematol ; 26(1): 73-8, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9430516

RESUMEN

Enumeration of CD34+ cells by flow cytometry is the recognized standard for quantitating progenitor cells for peripheral blood progenitor cell (PBPC) transplantation. Although many clinical studies have confirmed that the time to neutrophil and platelet engraftment is inversely proportional to the number of CD34+ cells infused, the minimum number of CD34+ cells necessary to acheive rapid engraftment has not been satisfactorily determined. The lack of a standardized method for quantitation of CD34+ cells by flow cytometry (FCM) is often cited as the reason for this ambiguity. This report describes an FCM method for CD34+ cell determination that is simple, highly reproducible, comparatively inexpensive, and validated by excellent correlation with clinical engraftment. Pheresis samples are stained and fixed within 4 hours of collection. Two hundred fifty thousand events are acquired as list mode data using a forward scatter threshold. The discrete CD34+ population is enumerated using a CD34-phycoerythrin FL2 vs. side scatter plot and Paint-A-Gate Pro software. The method was validated by excellent statistical correlation with clinical engraftment. Using this method, we determined the number of CD34+ progenitor cells necessary to achieve rapid engraftment to be 2 x 10(6)/kg.


Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/patología , Antígenos CD34 , Supervivencia de Injerto , Neoplasias Hematológicas/terapia , Humanos , Trasplante Autólogo
17.
Bone Marrow Transplant ; 50(10): 1326-30, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26191953

RESUMEN

The relationship of socioeconomic status (SES) with long-term outcomes in allogeneic hematopoietic cell transplantation (HCT) survivors has not been well described. We studied the association of SES with the outcomes of 283 consecutive allogeneic HCT recipients transplanted between 2003 and 2012 who had survived for at least 1 year in remission. Median annual household income was estimated using Census tract data and from ZIP code of residence. SES categories were determined by recursive partitioning analysis (low SES (<$51 000/year), N=203; high SES (⩾$51 000/year), N=80). In multivariable analyses, low SES patients had higher risks of all-cause mortality (hazard ratio (HR) 1.98, P=0.012) and non-relapse mortality (NRM) (HR 2.22, P=0.028), but similar risks of relapse mortality (HR 1.01, P=0.97) compared with high SES patients. A trend toward better survival and lower NRM for high SES patients with no chronic GVHD was observed; low SES patients without GVHD had similar survival as patients with chronic GVHD. In allogeneic HCT survivors who survive in remission for at least 1 year, SES is associated with long-term survival that is primarily mediated through higher risks of NRM. More research is needed to understand the mechanisms of health-care disparities and interventions to mitigate them.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/economía , Clase Social , Acondicionamiento Pretrasplante/economía , Trasplante Homólogo/economía , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Sobrevivientes , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Adulto Joven
18.
Bone Marrow Transplant ; 50(9): 1235-40, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26030045

RESUMEN

Quality of life (QOL) is an important outcome for hematopoietic cell transplantation (HCT) recipients. Whether pre-HCT QOL adds prognostic information to patient and disease related risk factors has not been well described. We investigated the association of pre-HCT QOL with relapse, non-relapse mortality (NRM), and overall mortality after allogeneic HCT. From 2003 to 2012, the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale instrument was administered before transplantation to 409 first allogeneic HCT recipients. We examined the association of the three outcomes with (1) individual QOL domains, (2) trial outcome index (TOI) and (3) total score. In multivariable models with individual domains, functional well-being (hazard ratio (HR) 0.95, P=0.025) and additional concerns (HR 1.39, P=0.002) were associated with reduced risk of relapse, no domain was associated with NRM, and better physical well-being was associated with reduced risk of overall mortality (HR 0.97, P=0.04). TOI was not associated with relapse or NRM but was associated with reduced risk of overall mortality (HR 0.93, P=0.05). Total score was not associated with any of the three outcomes. HCT-comorbidity index score was prognostic for greater risk of relapse and mortality but not NRM. QOL assessments, particularly physical functioning and functional well-being, may provide independent prognostic information beyond standard clinical measures in allogeneic HCT recipients.


Asunto(s)
Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Calidad de Vida , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia
19.
Leukemia ; 29(8): 1754-62, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25772027

RESUMEN

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.


Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Disfunción Primaria del Injerto/etiología , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos , Estadificación de Neoplasias , Disfunción Primaria del Injerto/tratamiento farmacológico , Disfunción Primaria del Injerto/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo , Adulto Joven
20.
Semin Oncol ; 21(4 Suppl 7): 86-95, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7916488

RESUMEN

Autologous bone marrow transplantation has curative potential in patients with both Hodgkin's disease and non-Hodgkin's lymphoma who have relapsed following conventional therapy. Autologous bone marrow transplantation allows administration of higher doses of chemotherapy, radiation therapy, or combined-modality therapy than is otherwise possible, often resulting in increased cure rates (20% to 50%) versus standard-dose therapy. In the past, transplanted marrow cells required 3 weeks to proliferate, leaving the pancytopenic patient prone to bleeding and infections, as well as nonhematologic toxicity caused by the high-dose therapeutic intervention; mortality rates from autologous bone marrow transplantation were 10% to 20%. Now, however, the use of hematopoietic growth factors with primed peripheral blood progenitor cells has resulted in rapid marrow engraftment and a reduction in induction mortality rates to less than 5%. Studies investigating the use of newer hematopoietic growth factors, as well as applying autologous bone marrow transplantation in high-risk remission patients, are currently ongoing.


Asunto(s)
Trasplante de Médula Ósea , Enfermedad de Hodgkin/terapia , Linfoma no Hodgkin/terapia , Terapia Recuperativa , Ensayos Clínicos como Asunto , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante Autólogo , Insuficiencia del Tratamiento
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