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1.
Blood ; 137(4): 556-568, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33104215

RESUMEN

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Pobreza , Determinantes Sociales de la Salud , Adolescente , Causas de Muerte , Niño , Preescolar , Enfermedad Crónica/mortalidad , Enfermedad Crónica/terapia , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/mortalidad , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Lactante , Infecciones/epidemiología , Cobertura del Seguro/estadística & datos numéricos , Masculino , Medicaid , Neoplasias/mortalidad , Neoplasias/terapia , Recurrencia , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Estados Unidos
2.
J Oncol Pharm Pract ; 29(1): 45-51, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34816754

RESUMEN

INTRODUCTION: Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization. METHODS: This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends. RESULTS: The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, P = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, P = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, P = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups. CONCLUSION: Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.


Asunto(s)
Síndrome de Liberación de Citoquinas , Hospitalización , Humanos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Glucocorticoides/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos
3.
Biol Blood Marrow Transplant ; 26(10): 1930-1936, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32649981

RESUMEN

Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P < .0001). The 2-year incidence of transplantation-related mortality adjusted for age and conditioning regimen intensity was higher after umbilical cord blood transplantation compared with HLA-haploidentical related donor transplantation (31% versus 18%; P = .008); however, there were no between-group differences in the 2-year adjusted incidence of relapse (30% versus 34%; P = .51), overall survival (54% versus 57%; P = .66), or disease-free survival (43% versus 47%; P = .46). Our findings show that the use of HLA-haploidentical and umbilical cord blood transplants expands the access to transplantation with comparable leukemia-free and overall survival for African Americans with hematologic malignancies.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Negro o Afroamericano , Sangre Fetal , Neoplasias Hematológicas/terapia , Prueba de Histocompatibilidad , Humanos
4.
Cancer ; 126(23): 5077-5087, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32965680

RESUMEN

BACKGROUND: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. METHODS: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. RESULTS: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P = .02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P = .003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P = .003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P = .01]), likely representing frailty. CONCLUSIONS: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Trasplante Autólogo/métodos , Resultado del Tratamiento , Estados Unidos
5.
Br J Haematol ; 190(6): 851-853, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32358811

RESUMEN

Seldom has a medical advance in cancer therapy been as pivotal as the advent of chimeric antigen receptor (CAR)-T-cell immunotherapy. While the first applications targeted the CD19 antigen on lymphoid malignancies, the incredible specificity of these 'living drugs', curative potential and generalisability to other targets have richly justified their declaration as 2019's breakthrough of the year by Science magazine. Two CAR-T products, Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel) were Food and Drug Administration (FDA)-approved in the USA in late 2017, with the FDA commissioner Scott Gottlieb heralding 'a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer'. Building upon early enthusiasm, nearly 1000 cell- and gene-therapy investigational new drug applications are pending with the FDA, which expects to review and approve between 10 and 20 such treatments annually by 2025. Despite the enormous promise and urgent unmet need fulfilled by CAR-T cells, the real-world adoption of the two FDA-approved treatments has been slow.


Asunto(s)
Antígenos CD19/uso terapéutico , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T/uso terapéutico , Receptores Quiméricos de Antígenos/uso terapéutico , Productos Biológicos , Humanos , Inmunoterapia Adoptiva , Neoplasias/inmunología , Receptores Quiméricos de Antígenos/inmunología , Estados Unidos , United States Food and Drug Administration
6.
J Am Acad Dermatol ; 83(3): 762-772, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31654664

RESUMEN

BACKGROUND: Melanoma risk is increased after allogeneic hematopoietic cell transplantation (HCT), but specific risk factors are unknown. OBJECTIVE: Investigate risk factors for melanoma after allogeneic hematopoietic cell transplantation. METHODS: We conducted a nested case-control study of 140 melanoma cases and 557 controls (matched by age at HCT, sex, primary disease, survival time) through the Center for International Blood and Marrow Transplant Research. RESULTS: Melanoma risk was significantly increased among HCT survivors who received total body irradiation-based myeloablative conditioning (multivariable adjusted odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.00-3.15) or reduced-intensity conditioning containing melphalan (OR = 2.60; 95% CI = 1.13-6.02) or fludarabine (OR = 2.72; 95% CI = 1.02-7.30) versus busulfan-based myeloablative regimens; were diagnosed with acute graft-versus-host disease (GVHD) with stage 2+ skin involvement (OR = 1.92; 95% CI = 1.19-3.10), chronic GvHD without skin involvement (OR = 1.91; 95% CI = 1.03-3.57), or keratinocytic carcinoma (OR = 2.37; 95% CI = 1.16-4.83); and resided in areas with higher ambient ultraviolet radiation (ORtertile3 = 1.64; 95% CI = 1.01-2.67). LIMITATIONS: Data on individual-level ultraviolet radiation exposure and clinical data on melanoma characteristics were lacking. Additionally, misclassification of melanoma is possible as not all pathology reports were available for review. CONCLUSION: These results emphasize the importance of adherence to current surveillance guidelines (routine skin examination, photoprotection recommendations), particularly for HCT survivors at highest risk.


Asunto(s)
Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Busulfano/efectos adversos , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Lactante , Estado de Ejecución de Karnofsky/estadística & datos numéricos , Masculino , Melanoma/diagnóstico , Melanoma/etiología , Melanoma/patología , Melfalán/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Factores de Riesgo , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Donantes de Tejidos/estadística & datos numéricos , Acondicionamiento Pretrasplante/métodos , Rayos Ultravioleta/efectos adversos , Vidarabina/efectos adversos , Vidarabina/análogos & derivados , Irradiación Corporal Total/efectos adversos , Adulto Joven
7.
Biol Blood Marrow Transplant ; 25(11): e331-e343, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31394266

RESUMEN

Optimum care of female transplant recipients requires gynecologic care at several stages through the allogeneic hematopoietic stem cell transplantation (HCT) process. Sex-based considerations in women post-HCT span gynecologic sequelae of transplant along with assessment and maintenance of optimal sexual and gynecologic health. Pre-HCT, managing menstruation and abnormal uterine or genital bleeding, considering fertility preservation, and assessing for sexually transmitted infections, including human papillomavirus (HPV)-related disease and cervical cancer, enhance women's health. While inpatient during transplant when women are thrombocytopenic, menstrual bleeding requires suppression. Whenever graft-versus-host disease (GVHD) is assessed, screening for genital GVHD merits consideration. After the first 100 days, periodic assessments include obtaining a menstrual history, assessing ovarian function, and reviewing current hormonal use and contraindications to hormonal methods. Regular assessment for primary ovarian insufficiency, dyspareunia, and intimacy guides provision of contraception and hormone replacement options. As part of ongoing screening for genital GVHD and HPV-related disease, including sexually transmitted infections, periodic pelvic examinations are performed. Once successful long-term survival is achieved, planning for fertility may be considered. This article offers a comprehensive approach to these aspects of gynecologic care of patients throughout the trajectory of HCT and beyond into survivorship. We review the effects of HCT treatment on sexual health, ovarian function, and resulting menstrual changes and fertility challenges. Identification, treatment, and prevention of subsequent malignancies, including breast cancer, are discussed, with a focus on regular assessment of genital HPV disease and GVHD in long-term follow-up.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Salud Reproductiva , Salud de la Mujer , Anticoncepción , Femenino , Humanos , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , Enfermedades Virales de Transmisión Sexual/prevención & control , Neoplasias del Cuello Uterino/prevención & control
8.
Biol Blood Marrow Transplant ; 25(2): 216-222, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30292745

RESUMEN

Blockade of the T-cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematologic malignancy after allogeneic stem cell transplantation limits the success of this approach, and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its relationship with post-transplant relapse is poorly described. Because the donor immunity is activated by alloresponses, PD-1 expression may differ from nontransplanted individuals, and PD-1 blockade could risk graft-versus-host disease. Here we analyzed T-cell exhaustion marker kinetics and their relationship with leukemia relapse in 85 patients undergoing myeloablative T-cell-depleted HLA-matched stem cell transplantation. At a median follow-up of 3.5 years, 35 (44%) patients relapsed. PD-1 expression in CD4 and CD8 T cells was comparably elevated in relapsed and nonrelapsed cohorts. Helios+ regulatory T cells and CD8 effector memory cells at day 30 emerged as independent predictors of relapse. Although leukemia antigen-specific T cells did not overexpress PD-1, single-cell analysis revealed LAG3 and TIM3 overexpression at relapse. These findings indicate that PD-1 is an unreliable marker for leukemia-specific T-cell exhaustion in relapsing patients but implies other exhaustion markers and suppressor cells as relapse biomarkers.


Asunto(s)
Biomarcadores de Tumor/inmunología , Regulación Leucémica de la Expresión Génica/inmunología , Leucemia , Proteínas de Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Trasplante de Células Madre , Adulto , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia/inmunología , Leucemia/mortalidad , Leucemia/patología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Recurrencia , Tasa de Supervivencia
9.
Biol Blood Marrow Transplant ; 25(3): 577-586, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30342913

RESUMEN

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.


Asunto(s)
Infecciones por Citomegalovirus/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adulto , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/etiología , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , National Institutes of Health (U.S.) , Estudios Retrospectivos , Factores de Riesgo , Esteroides/efectos adversos , Donantes de Tejidos , Estados Unidos
10.
Biol Blood Marrow Transplant ; 25(2): e46-e54, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30481594

RESUMEN

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.


Asunto(s)
Oftalmopatías , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Médula Ósea , Europa (Continente) , Oftalmopatías/metabolismo , Oftalmopatías/patología , Oftalmopatías/fisiopatología , Oftalmopatías/prevención & control , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/fisiopatología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Factores de Riesgo , Sociedades Médicas , Trasplante Homólogo
11.
Biol Blood Marrow Transplant ; 25(5): e145-e154, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30521975

RESUMEN

Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.


Asunto(s)
Oftalmopatías/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Oftalmopatías/diagnóstico , Oftalmopatías/prevención & control , Oftalmopatías/terapia , Humanos , Incidencia , Tamizaje Masivo , Grupo de Atención al Paciente , Factores de Riesgo
12.
Biol Blood Marrow Transplant ; 25(3): 480-487, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30423481

RESUMEN

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.


Asunto(s)
Antineoplásicos/administración & dosificación , Cálculo de Dosificación de Drogas , Trasplante de Células Madre Hematopoyéticas/métodos , Obesidad , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Linfoma/tratamiento farmacológico , Linfoma/mortalidad , Linfoma/terapia , Masculino , Persona de Mediana Edad , Mortalidad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Recurrencia , Trasplante Autólogo
13.
Biol Blood Marrow Transplant ; 25(2): 362-368, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30287390

RESUMEN

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Terapia de Inmunosupresión/efectos adversos , Infecciones/mortalidad , Leucemia Mieloide Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Factores de Tiempo
14.
Blood ; 130(9): 1156-1164, 2017 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-28674027

RESUMEN

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Anciano , Estudios de Cohortes , Demografía , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Análisis Multivariante , Pronóstico , Factores de Tiempo , Trasplante Homólogo/mortalidad , Resultado del Tratamiento , Estados Unidos
15.
Transpl Infect Dis ; 21(5): e13145, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31301099

RESUMEN

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos  = 222, 83%; EBVneg  = 45, 17%) were analyzed. RESULTS: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS: There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.


Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/etiología , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Herpesvirus Humano 4/genética , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos , Carga Viral , Adulto Joven
16.
Biol Blood Marrow Transplant ; 24(3): 460-466, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29197677

RESUMEN

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3+CD19+ cell depletion (CD3/19D) versus CD34+ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios- FoxP3+Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.


Asunto(s)
Antígenos CD19/inmunología , Antígenos CD34/inmunología , Neoplasias Hematológicas , Depleción Linfocítica , Trasplante de Células Madre de Sangre Periférica , Hermanos , Linfocitos T Colaboradores-Inductores/inmunología , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Aloinjertos , Niño , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
17.
Biol Blood Marrow Transplant ; 24(2): 228-241, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28939455

RESUMEN

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Neurocognitivos/etiología , Biomarcadores , Humanos , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/prevención & control , Trastornos Neurocognitivos/terapia , Prevalencia , Factores de Riesgo
18.
Cancer ; 124(4): 816-825, 2018 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29125192

RESUMEN

BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described. METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for ≥2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years. RESULTS: The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population. CONCLUSIONS: Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications. Cancer 2018;124:816-25. © 2017 American Cancer Society.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Factores de Tiempo , Trasplante Autólogo , Adulto Joven
19.
Blood ; 127(20): 2427-38, 2016 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-26884374

RESUMEN

Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for International Blood and Marrow Transplant Research (CIBMTR) Database was interrogated to analyze the impact of CMV reactivation on hematologic disease relapse in the current era. Data from 9469 patients transplanted with bone marrow or peripheral blood between 2003 and 2010 were analyzed according to 4 disease categories: AML (n = 5310); acute lymphoblastic leukemia (ALL, n = 1883); chronic myeloid leukemia (CML, n = 1079); and myelodysplastic syndrome (MDS, n = 1197). Median time to initial CMV reactivation was 41 days (range, 1-362 days). CMV reactivation had no preventive effect on hematologic disease relapse irrespective of diagnosis. Moreover, CMV reactivation was associated with higher nonrelapse mortality [relative risk [RR] among disease categories ranged from 1.61 to 1.95 and P values from .0002 to <.0001; 95% confidence interval [CI], 1.14-2.61). As a result, CMV reactivation was associated with lower overall survival for AML (RR = 1.27; 95% CI, 1.17-1.38; P <.0001), ALL (RR = 1.46; 95% CI, 1.25-1.71; P <.0001), CML (RR = 1.49; 95% CI, 1.19-1.88; P = .0005), and MDS (RR = 1.31; 95% CI, 1.09-1.57; P = .003). In conclusion, CMV reactivation continues to remain a risk factor for poor posttransplant outcomes and does not seem to confer protection against hematologic disease relapse.


Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Infecciones por Citomegalovirus/virología , Citomegalovirus/fisiología , Leucemia/terapia , Síndromes Mielodisplásicos/terapia , Activación Viral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/tratamiento farmacológico , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Lactante , Estimación de Kaplan-Meier , Leucemia/complicaciones , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Recurrencia , Sistema de Registros , Factores de Tiempo , Acondicionamiento Pretrasplante/efectos adversos , Adulto Joven
20.
Biol Blood Marrow Transplant ; 23(2): 184-192, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27818318

RESUMEN

The number of survivors after hematopoietic cell transplantation (HCT) is expected to dramatically increase over the next decade. Significant and unique challenges confront survivors for decades after their underlying indication (malignancy or marrow failure) has been cured by HCT. The National Institutes of Health (NIH) Late Effects Consensus Conference in June 2016 brought together international experts in the field to plan the next phase of survivorship efforts. Working groups laid out the roadmap for collaborative research and health care delivery. Potentially lethal late effects (cardiac/vascular, subsequent neoplasms, and infectious), patient-centered outcomes, health care delivery, and research methodology are highlighted here. Important recommendations from the NIH Consensus Conference provide fresh perspectives for the future. As HCT evolves into a safer and higher-volume procedure, this marks a time for concerted action to ensure that no survivor is left behind.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Sobrevivientes/estadística & datos numéricos , Adulto , Aloinjertos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Renta , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Estudios Retrospectivos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/etiología , Estrés Psicológico/epidemiología , Estrés Psicológico/etiología , Suicidio/estadística & datos numéricos , Análisis de Supervivencia , Sobrevivientes/psicología , Acondicionamiento Pretrasplante/efectos adversos , Desempleo
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