RESUMEN
ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We report the phase 1 results. After fludarabine-cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2 × 106, 1 × 106, or 0.5 × 106 cells per kg. The rate of dose-limiting toxicities (DLTs) within 28 days after KTE-X19 infusion was the primary end point. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age, 46 years; range, 18-77 years). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 31% and 38% of patients, respectively. To optimize the risk-benefit ratio, revised adverse event (AE) management for CRS and NEs (earlier steroid use for NEs and tocilizumab only for CRS) was evaluated at 1 × 106 cells per kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NEs, with no grade 4 or 5 NEs. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1 × 106 cells per kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At a median follow-up of 22.1 months (range, 7.1-36.1 months), the median duration of remission was 17.6 months (95% confidence interval [CI], 5.8-17.6 months) in patients treated with 1 × 106 cells per kg and 14.5 months (95% CI, 5.8-18.1 months) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1 × 106 cells per kg with revised AE management. This trial is registered at www.clinicaltrials.gov as #NCT02614066.
Asunto(s)
Antígenos CD19/metabolismo , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Síndrome de Liberación de Citoquinas/inducido químicamente , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inmunoterapia Adoptiva/efectos adversos , Mediadores de Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Neoplasia Residual/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
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 RiesgoRESUMEN
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.
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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 JovenRESUMEN
Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.
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Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Factores de Edad , Aloinjertos , Preescolar , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Tasa de SupervivenciaRESUMEN
BACKGROUND: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. METHODS: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. RESULTS: The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). CONCLUSION: Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications. Cancer 2017;123:1828-1838. © 2017 American Cancer Society.
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Depresión/psicología , Trastorno Depresivo/psicología , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas , Leucemia/terapia , Linfoma/terapia , Mieloma Múltiple/terapia , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Leucemia/psicología , Linfoma/psicología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/psicología , Análisis Multivariante , Síndromes Mielodisplásicos/psicología , Pronóstico , Modelos de Riesgos Proporcionales , Acondicionamiento Pretrasplante , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: A reason for empathy decline during medical training has not been fully elucidated. Empathy may decrease acutely during an inpatient hematology-oncology rotation because of the acuity of death exposures. This study aimed to explore physician trainee empathy, distress, death exposures, and their attributed meaning for the trainee. METHODS: Internal medicine interns and residents at a single academic center were evaluated before and after hematology-oncology ward rotations using Interpersonal Reactivity Index for empathy, previously cited reasons for empathy decline, Impact of Event Scale-Revised for distress, death exposures (no. of dying patients cared for) and attributed sense of meaning (yes/no) (post-rotation). RESULTS: Fifty-six trainees completed both pre-rotation and post-rotation questionnaires (58% response). Empathy averaged 58.9 (SD 12.0) before and 56.8 (SD 11.1) after the rotation (2.1 point decrease) (p = 0.018). Distress was elevated but did not change significantly during the rotation. Residents cared for 4.28 dying patients. Seventy-three percent reported that death was the most stressful event during the rotation, yet 68% reported that they derived a sense of meaning from caring for dying patients. Empathy and distress scales were positively correlated before the rotation (r = 0.277, p = 0.041) but not after (r = .059, p = 0.69). CONCLUSION: This study suggests that an acute drop in empathy can occur over several weeks in residents rotating through inpatient hematology-oncology, similar to empathy decline associated with years of training in other studies. Empathy decline may be associated with elevated distress and death exposures on the hematology-oncology ward and should be explored further in other medical training environments. Copyright © 2016 John Wiley & Sons, Ltd.
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Actitud del Personal de Salud , Empatía , Internado y Residencia , Resiliencia Psicológica , Adulto , Femenino , Neoplasias Hematológicas/psicología , Humanos , Masculino , Oncología Médica , Encuestas y CuestionariosRESUMEN
Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% of US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee-International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation standards resulting from the CIBMTR study would have significantly impacted practice. Accordingly, we conducted a follow-up survey of US transplantation centers to assess practice changes since 2007, and to investigate additional areas where RD care was predicted to differ from UD care. A total of 73 centers (53%), performing 79% of RD transplantations in the United States, responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P < .0001). This study identifies several areas where RD management does not meet international donor care standards, however. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are made.
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Adhesión a Directriz/normas , Hospitales Especializados/normas , Pautas de la Práctica en Medicina/normas , Donantes de Tejidos , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Estados UnidosRESUMEN
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
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Enfermedades Cardiovasculares/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Metabólico/etiología , Enfermedades Cardiovasculares/diagnóstico , Humanos , Síndrome Metabólico/diagnóstico , Factores de Riesgo , Trasplante HomólogoRESUMEN
Assessment with (18)F-fluorodeoxy glucose (FDG)-positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non-Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with increased mortality (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL.
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Fluorodesoxiglucosa F18/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Tomografía de Emisión de Positrones , Adolescente , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Tasa de SupervivenciaRESUMEN
We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients.
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Trasplante de Células Madre Hematopoyéticas , Agonistas Mieloablativos/uso terapéutico , Mielofibrosis Primaria/terapia , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Estudios de Cohortes , Femenino , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mielofibrosis Primaria/inmunología , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/patología , Pronóstico , Recurrencia , Riesgo , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Donante no Emparentado/clasificaciónRESUMEN
ABSTRACT: We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.
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Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria , Humanos , Mielofibrosis Primaria/terapia , Mielofibrosis Primaria/mortalidad , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Acondicionamiento Pretrasplante/métodos , Anciano , Enfermedad Injerto contra Huésped/etiología , Donantes de Tejidos , Sistema de Registros , Donante no EmparentadoRESUMEN
Rapid advances in the field of hematopoietic cell transplantation (HCT), as well as the advent of immune effector cell therapy (IEC), have resulted in an increasing number of patients undergoing these therapies and an increasing level of expertise required to manage them. Previous guidelines for the training of HCT physicians were last published in 2012. In recognition of the expanding knowledge base and increasing skill set essential to the delivery of these treatment modalities, the American Society for Transplantation and Cellular Therapy Committee on Education has updated these guidelines to reflect nearly a decade of new knowledge in the field of HCT, as well as the evolution of IEC from an experimental modality to a widely used and mainstream therapy. The resulting document reflects the Committee on Education's recommended educational structure for programs engaged in the training, evaluation, and mentorship of HCT/IEC trainees.
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Becas , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfocitos , Acondicionamiento Pretrasplante/métodos , Estados UnidosRESUMEN
A patient with relapsed/refractory B-cell acute lymphoblastic leukemia developed babesiosis before allogeneic hematopoietic cell transplantation while on atovaquone for Pneumocystis jirovecii pneumonia prophylaxis. Despite receiving a prolonged course of atovaquone and azithromycin until whole-blood Babesia microti DNA was no longer detected by polymerase chain reaction, her post-transplant course was complicated by relapsed babesiosis. We investigate the potential host and parasite characteristics causing relapsing/persistent infection.
RESUMEN
Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.
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Trasplante de Células Madre Hematopoyéticas , Reinserción al Trabajo , Femenino , Humanos , Recurrencia Local de Neoplasia , Sobrevivientes , Trasplante Homólogo , Estados Unidos , Adulto JovenRESUMEN
Plasmablastic lymphoma (PBL) and plasmablastic plasma cell myeloma (PCM) have many overlapping characteristics. Clinical correlation can help make the distinction between the two entities. Human immunodeficiency virus- (HIV-) negative PBL is a rare disease, making the diagnosis more challenging. While there is no standard of care for PBL, current recommendations include dose-adjusted EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone), with or without bortezomib. We report an aggressive case of HIV-negative plasmablastic lymphoma and discuss the challenge in establishing a diagnosis. We review the literature regarding this disease and current recommendations for treatment.
RESUMEN
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following 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 following 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 to 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. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.
Asunto(s)
Disfunción Cognitiva/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/terapia , Humanos , Efectos Adversos a Largo Plazo , Calidad de Vida , Factores de Riesgo , Receptores de TrasplantesRESUMEN
PURPOSE: To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). PATIENTS AND METHODS: We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. RESULTS: Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 10(9)/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. CONCLUSION: The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Síndromes Mielodisplásicos/terapia , Adolescente , Adulto , Anciano , Femenino , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Trasplante HomólogoRESUMEN
The presentation of a MALT lymphoma in the bladder is exceedingly rare. Furthermore, the optimal treatment of primary MALT confined to the bladder remains to be defined. Here, we report a case of a 65-year-old female with primary MALT lymphoma treated with definitive radiation therapy. The patient received a total dose of 30 Gy in 20 equal daily fractions to the bladder and tolerated the treatment well. In addition, we have extensively reviewed the relevant literature to better define the optimal management of this rare disease. In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy with excellent prognosis if detected at an early stage. For early stage disease, definitive radiation represents an excellent treatment modality with a minimal side-effect profile.
RESUMEN
The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material[1]. Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18) chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases), the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities.