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ABSTRACT: Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse-enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.
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Neoplasias del Sistema Nervioso Central , Humanos , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/secundario , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Linfoma de Células T/patología , Linfoma de Células T/diagnóstico , Linfoma de Células T/mortalidad , Pronóstico , Anciano de 80 o más Años , Recurrencia Local de Neoplasia , Linfoma Extranodal de Células NK-T/diagnóstico , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/terapia , Factores de Riesgo , Recurrencia , Células Asesinas Naturales , Adulto JovenRESUMEN
Cutaneous T-cell lymphoma (CTCL) is a rare hematologic malignancy that traditionally presents with cutaneous lesions, though metastases are not uncommon in progressive disease. We describe four cases of CTCL with central nervous system (CNS) involvement, detailing the history, pathological characteristics, treatment response, and progression. Median time from initial diagnosis to CNS metastasis was â¼5.4 years (range 3.4-15.5 years) and survival after metastasis was â¼160 days (range 19 days-4.4 years). No patients achieved long-term (>5 years) survival, though some displayed varying degrees of remission following CNS-directed therapy. We conclude that clinicians must be attentive to the development of CNS metastases in patients with CTCL. The growing body of literature on such cases will inform evolving therapeutic guidelines on this rare CTCL complication.
Cutaneous T-cell lymphoma (CTCL) is a rare cancer of the blood, which typically manifests with skin lesions, such as itchy, scaly rashes that may thicken to form tumors on the skin. Though uncommon, metastases do occur in CTCL. A particularly rare location for these metastases is the central nervous system. This case series recounts the story of four unique patients and the presentation, diagnosis, and treatment of their CTCL, which unfortunately progressed to involve the central nervous system. Outcomes with central nervous system involvement in CTCL are poor, but may occur sometime later than a patient's initial diagnosis. Our patients had a median time from initial diagnosis to central nervous system metastases of â¼5.4 years and a survival of â¼160 days after central nervous system metastases. Some types of therapy, such as radiation, surgery, or chemotherapy, may be beneficial in extending survival or providing symptomatic relief for patients. It can be difficult to recognize symptoms of central nervous system metastases, so this case series emphasizes that vigilance for potential metastases and use of interdisciplinary teams is important in caring for these patients. This case series demonstrates the importance of continued research in this area, with the hope of improving outcomes for patients with central nervous system metastases of CTCL.
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Linfoma Cutáneo de Células T , Neoplasias Primarias Secundarias , Neoplasias Cutáneas , Humanos , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Neoplasias Cutáneas/patologíaRESUMEN
INTRODUCTION: Visceral involvement of cutaneous T-cell lymphoma (vCTCL) is a rare but poorly studied complication of CTCL. We aimed to assess clinical characteristics, treatment, and outcomes, associated with vCTCL at our institution. METHODS: We conducted a retrospective review of patients with vCTCL among patients with a confirmed histopathologic diagnosis of CTCL seen at the Winship Cancer Institute in Emory University. vCTCL was defined as a highest TNMB stage of 4B with extracutaneous metastatic disease (M1) pathologically confirmed or strongly clinically suspected based on imaging, symptoms, and the clinical judgment of the treating physician. Patients were selected from our CTCL database containing 656 patients from 1990 to 2022. Clinical characteristics were characterized. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curve and univariable Cox regression analysis. RESULTS: Twenty-six of 656 patients with vCTCL were identified. 42.3% of patients were black. Twenty-two patients were diagnosed with MF/SS and 4 had other CTCL subtypes including pcALCL, Gamma-Delta, and Cytotoxic T-Cell Lymphoma. The median PFS and OS were 7.3 months (3.8, 11) and 12.1 months (9.9, 18.2), respectively. Median time to metastasis from initial diagnosis was 12.1 months. The most common M1 sites were liver (19.2%) and lung (42.3%). M1 sites outside of liver or lung were associated with inferior OS (HR 8.9, 95%CI: 2.7-29.5, P-value <.001) and PFS (HR 4.3, 95%CI: 1.44-12.7, P-value = .009). No treatments or baseline factors were associated with improved survival. CONCLUSION: Our retrospective study confirms therapy resistance and dismal outcomes among patients with vCTCL.
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Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Micosis Fungoide/patología , Síndrome de Sézary/patología , Neoplasias Cutáneas/diagnóstico , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/patologíaRESUMEN
Importance: To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant. Objective: To evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma. Design, Setting, and Participants: A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT. Interventions: Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment. Main Outcomes and Measures: The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety. Results: Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting. Conclusions and Relevance: Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant. Trial Registration: ClinicalTrials.gov Identifier: NCT03077828.
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Enfermedad de Hodgkin , Humanos , Femenino , Adulto , Masculino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Ifosfamida/efectos adversos , Carboplatino/uso terapéutico , Etopósido , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Recuperativa/métodosRESUMEN
BACKGROUND: Risk factors for progression to advanced-stage mycosis fungoides (MF) are poorly defined. METHODS: The authors performed a single-center, retrospective cohort study among patients with MF at an academic medical center from 1990 to 2020 to identify clinical variables associated with progression to advanced-stage MF (stage IIB-IVB), and 388 patients who had a clinicopathologic diagnosis of early stage (IA-IIA) MF were identified from their cutaneous lymphoma database. Baseline clinical characteristics, laboratory values, imaging, and blood flow cytometry or T-cell receptor gene rearrangement (TCR) data were collected. Logistic regression was used to assess risk factors associated with progression. RESULTS: Overall, 93 of 388 patients (24.0%) progressed to advanced stage. Patients who progressed had an increased risk of death (hazard ratio, 4.50; 95% CI, 2.89-7.00; p < .001). Progression was associated with a higher overall stage at diagnosis, tumor stage, lymph node stage, low-level blood involvement, as measured with TCR data and/or flow cytometry, and elevated lactate dehydrogenase (LDH). Limitations included missing data for LDH, imaging, peripheral blood TCR data, or flow cytometry assessed at diagnosis. CONCLUSIONS: Staging and baseline laboratory assessments with imaging, peripheral blood flow cytometry, TCR data, and LDH in patients who have newly diagnosed MF may identify those who are at risk for progression to advanced stage.
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Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Síndrome de Sézary/patología , Pronóstico , Estudios Retrospectivos , Estadificación de Neoplasias , Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/patología , Ganglios Linfáticos/patología , Receptores de Antígenos de Linfocitos TRESUMEN
Infections originating in the skin/soft tissue are a major cause of mortality in cutaneous T-cell lymphoma (CTCL). We performed a retrospective analysis to characterize cutaneous cultures and assess risk factors for bacteremia among 69 patients with CTCL. Cutaneous infections and antimicrobial resistance were common. Black race and lymph node involvement were associated with bacteremia. Mitigating strategies for invasive infections in CTCL remain unclear. HighlightsSkin/soft tissue infections are common in cutaneous T-cell lymphoma (CTCL).Black race, lymph node involvement, and positive cultures for S. aureus, Gram-negative bacteria, or multiple organisms were associated with an increased rate of bacteremia.The role of antimicrobial prophylaxis and staphylococcus decolonization is unclear.
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Bacteriemia , Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Staphylococcus aureus , Micosis Fungoide/patología , Síndrome de Sézary/patología , Estudios Retrospectivos , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/patología , Bacteriemia/etiologíaRESUMEN
In a multicenter, phase 2, investigator-initiated trial of sequential pembrolizumab and AVD (doxorubicin, vinblastine, and dacarbazine), nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma (cHL) achieved positron emission tomography (PET)-defined, complete or near-complete metabolic responses (CMRs), following pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD, with 100% of patients alive and without relapse at initial publication. We now report long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received 3 cycles of single-agent pembrolizumab, followed by AVD chemotherapy for 4 to 6 cycles depending on the stage and bulk. PET/computed tomography scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and programmed cell death protein 1 (PD-1) pathway markers. At a median follow-up of 33.1 months (range, 26.0-43.0), progression-free survival and OS remained 100%. All patients had genomic alterations in 9p24.1 and were positive for programmed death ligand 1 (PD-L1) by immunohistochemistry. There was no relationship between depth of response to single-agent pembrolizumab and 9p24.1 alterations or PD-1 pathway H-scores. After additional follow-up, sequential pembrolizumab and AVD remained highly effective. The high response rates observed at all PD-L1 levels suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase 2 trial (registered at www.clinicaltrials.gov as #NCT03226249) is ongoing to confirm our findings.
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/terapia , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1 , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard first-line treatment for fit patients with mantle cell lymphoma (MCL). We conducted a single-center phase I trial investigating post-transplant maintenance with ixazomib, an oral proteasome inhibitor. METHODS: Patients enrolled between days +70 and +180 post ASCT. Patients received ixazomib per dose cohort on days 1, 8, and 15 of each 28-day cycle for up to 10 cycles. During recruitment, published phase III data reported a survival benefit with rituximab maintenance, so all subsequent patients received ixazomib 4 mg at the same schedule along with rituximab 375 mg/m2 on day 1 of cycles 1, 3, 5, 7, and 9. All patients were in complete remission at enrollment. RESULTS: Seven patients received ixazomib monotherapy; 1 dose limiting toxicity (grade 3 neutropenia) occurred at dose level 2 (4 mg). Five patients received combination Ixazomib plus rituximab, with 2 experiencing DLTs (both Grade 4 neutropenia). Grade 3-4 neutropenia, lymphopenia, and thrombocytopenia occurred in 57%, 8%, and 8% of patients, respectively. Non-hematologic adverse events (AE) included nausea (42%), peripheral neuropathy (42%), and abdominal discomfort (33%), all of which were grade 1 or 2 in severity. There were no infectious AEs. With a median follow up of 46 months, all patients are alive and in complete remission. CONCLUSION: The trial was closed to further accrual due to high rates of treatment-related myelosuppression. The current dose and schedule of ixazomib, especially when combined with rituximab, results in unacceptable hematologic toxicity when administered as post-transplant maintenance in MCL. Ixazomib maintenance micro abstract: The authors conducted a phase I study investigating the use of ixazomib, an oral proteasome inhibitor, with or without rituximab in patients with mantle cell lymphoma in first remission following chemoimmunotherapy and autologous stem cell transplantation. All patients treated on study remain in complete remission with a median follow-up of 46 months, but the study was closed early due to a high rate of hematologic adverse events.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Neutropenia , Humanos , Adulto , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/patología , Rituximab/uso terapéutico , Trasplante Autólogo , Inhibidores de Proteasoma/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Importance: Mycosis fungoides and Sézary syndrome (MF/SS) has an increased incidence in Black patients, but clinical characteristics, treatments, and outcomes have been poorly characterized. Objective: To assess racial differences in presentation and outcome and identify drivers for racial disparities in MF/SS. Design, Setting, and Participants: A retrospective cohort analysis was conducted of 566 patients with MF/SS diagnosed from 1990 to 2020 and seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital, both in Atlanta, Georgia. Self-reported race and ethnicity were obtained from patient medical records and analyzed as 2 groups: non-Hispanic Black (Black) and all other races and ethnicities, including Asian, Hispanic, White, and unknown/undeclared (non-Black). Main Outcomes and Measures: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival and time to next treatment. The primary outcome was to assess differences in overall survival by racial and ethnic group. The hypotheses were formulated prior to data collection. Results: Of the 566 patients with MF/SS identified (mean [SD] age 55 [16.4] years; 270 (47.7%) female), 257 were Black and 309 were non-Black. Black race was associated with increased rates of progression to a higher TNMB stage (39.8% in Black patients vs 29.1% in non-Black patients; P < .001) but not survival. Black patients were younger and had increased female predominance, higher TNMB stage, higher tumor stage, nodal involvement, and higher lactate dehydrogenase level compared with non-Black patients with MF/SS. Hypopigmented MF (HMF) was found in 62 patients, who were mostly Black (n = 59). Hypopigmented MF was significantly associated with survival on univariate and multivariable models, with 10-year survival of 100% in patients with HMF compared with 51.8% in patients without HMF. Black race was only associated with inferior outcomes after excluding patients with HMF who were younger than 60 years (hazard ratio [HR], 1.61; 95% CI, 1.02-2.55; P = .04), but not in patients older than 60 years (HR, 1.20; 95% CI, 0.80-1.81; P = .37). On multivariate analysis, among the cohort without HMF who were younger than 60 years, Black race remained statistically significant when controlling for cancer stage and large-cell transformation (HR, 1.27; 95% CI, 1.08-2.87; P = .43). Conclusions and Relevance: In this cohort study, Black patients with MF/SS showed distinct clinical presentations and patterns of progression with heterogeneous outcomes depending on age at presentation and presence of HMF.
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Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/terapia , Síndrome de Sézary/patología , Etnicidad , Estudios Retrospectivos , Estudios de Cohortes , Neoplasias Cutáneas/patología , Pronóstico , Micosis Fungoide/diagnóstico , Micosis Fungoide/terapia , Micosis Fungoide/patología , Transformación Celular Neoplásica/patologíaRESUMEN
Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with poor survival. We performed a retrospective review of SS patients at Emory University from 1990 to 2020. We collected data on race, clinical characteristics, therapy, and social determinants of health. Clinical endpoints were overall survival (OS) and time to next treatment (TTNT). Univariate association and multivariable analyses were assessed by Cox proportional hazards models. Among 62 patients, 45.2% were AA. The median OS and TTNT were 3.1 years and 6.3 months, respectively, with no difference by race. AA patients had a higher median baseline LDH (360 vs. 232, p = 0.002) and a longer delay in initiation of systemic therapy compared to CC patients (3.17 vs. 2.14 months, p = 0.039), but a shorter commute (<10 miles) and no difference in insurance coverage (p = 0.260). AA patients at an academic center had unique clinical features and treatment patterns, but similar survival to CC SS patients.
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Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Negro o Afroamericano , Humanos , Micosis Fungoide/diagnóstico , Micosis Fungoide/epidemiología , Micosis Fungoide/terapia , Pronóstico , Estudios Retrospectivos , Síndrome de Sézary/tratamiento farmacológico , Síndrome de Sézary/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/terapiaRESUMEN
Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared to those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. NHL/CLL patients demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential.
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COVID-19 , Leucemia Linfocítica Crónica de Células B , Linfoma no Hodgkin , Humanos , SARS-CoV-2/genética , Vacunas contra la COVID-19 , COVID-19/prevención & control , Anticuerpos Neutralizantes , VacunaciónRESUMEN
IMPORTANCE: The prognostic significance of clonal T-cell receptor (TCR) rearrangement or low-level blood involvement as assessed by flow cytometry for patients with early-stage cutaneous T-cell lymphoma (CTCL) is not clear. OBJECTIVE: To assess the association of low-level blood involvement by TCR clonality and flow cytometry with outcomes for patients with early-stage CTCL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort analysis was conducted from September 1, 2019, to February 29, 2020, of 322 patients with early-stage (I-IIA) CTCL seen at the Winship Cancer Institute of Emory University and Grady Memorial Hospital. T-cell receptor gene rearrangement and flow cytometry records from the peripheral blood were documented at initial assessment. EXPOSURES: T-cell receptor clonality and peripheral blood flow cytometry. MAIN OUTCOMES AND MEASURES: Univariate and multivariable models and Kaplan-Meier assessments were analyzed for overall survival (OS) and time to next treatment. The primary outcome was OS from diagnosis and time to next treatment, and the hypotheses were formulated prior to data collection. RESULTS: A total of 322 patients (166 female patients [51.6%]; median age at diagnosis, 53.8 years [range, 8.6-87.4 years]) with early-stage CTCL diagnosed from 1990 to 2018 were identified; of these, 258 had data available for both flow cytometry and TCR. Positive results for both TCR clonality and flow cytometry were associated with inferior OS in early-stage CTCL compared with both having negative results (hazard ratio [HR], 2.86; 95% CI, 1.02-8.06; P = .046). Positive results for only TCR clonality or only flow cytometry were not associated with OS (TCR clonality: HR, 1.31; 95% CI, 0.70-2.47; P = .40; flow cytometry: HR, 1.21; 95% CI, 0.58-2.52; P = .61) or time to next treatment (TCR clonality: HR, 1.05; 95% CI, 0.77-1.43; P = .76; flow cytometry: HR, 0.74; 95% CI, 0.47-1.16; P = .12). However, positive flow cytometry results were associated with reduced OS in the stage IIA subgroup (n = 94; HR, 1.17; 95% CI, 1.18-8.74; P = .02). Covariates associated with reduced survival included advanced age at diagnosis, male sex, and higher disease stage. CONCLUSIONS AND RELEVANCE: This cohort study of patients with early-stage CTCL suggests that low-level blood involvement as indicated by positive results for both TCR gene rearrangement and flow cytometry was associated with inferior OS, whereas positive results for either flow cytometry or TCR clonality was not. More precise measurements of blood involvement in CTCL and larger multi-institutional cohorts are needed to validate the prognostic significance of low-level blood involvement in early-stage CTCL.
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Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Estudios de Cohortes , Femenino , Citometría de Flujo , Genes Codificadores de los Receptores de Linfocitos T , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/patología , Masculino , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaRESUMEN
Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dacarbazina/uso terapéutico , Doxorrubicina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Vinblastina/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dacarbazina/efectos adversos , Doxorrubicina/efectos adversos , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vinblastina/efectos adversosRESUMEN
Adolescents and young adults (AYAs) with cancer constitute approximately 70,000 patients diagnosed each year. Survival rates for AYAs with cancer have increased steadily in recent decades due to improvements in therapeutic regimens and early detection. Given the large and growing number of AYA cancer survivors, additional research is needed on the immediate and long-term psychosocial support required for this population including family planning and fertility. Fertility and fertility preservation in female AYAs, in particular, is historically understudied and has psychologically relevant ramifications distinct from male AYAs. Decision science can contribute to this area of oncological care and has implications for clinical encounters and research concerning female AYA patients with cancer. Patient-centered care and shared decision-making that integrates recent research regarding fertility preservation in the context of cancer.
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Toma de Decisiones , Preservación de la Fertilidad , Neoplasias/fisiopatología , Adolescente , Supervivientes de Cáncer/psicología , Femenino , Humanos , Neoplasias/psicología , Neoplasias/terapia , Atención Dirigida al Paciente , Adulto JovenRESUMEN
BACKGROUND: Treatment of cutaneous T-cell lymphoma (CTCL) with total skin electron beam (TSEB) therapy has been associated with deep responses but short progression-free intervals. Maintenance therapy might prolong the response duration; however, limited data assessing the outcomes with maintenance therapy after TSEB are available. We evaluated the effect of maintenance therapy on the outcomes for patients with CTCL receiving TSEB therapy. MATERIALS AND METHODS: We conducted a single-center retrospective analysis of 101 patients with CTCL who had received TSEB therapy from 1998 to 2018 at the Winship Cancer Institute of Emory University and compared the overall survival (OS) and progression-free survival (PFS) for patients had received maintenance therapy, including retinoids, interferon, ultraviolet therapy, nitrogen mustard, and extracorporeal photopheresis compared with those who had not. RESULTS: We found that pooled maintenance therapies improved PFS (hazard ratio [HR], 0.60; P = .026) but not OS (median HR, 0.73; P = .264). The median PFS and OS was 7.2 months versus 9.6 months and 2.4 years versus 4.2 years for the no maintenance and maintenance groups, respectively. On exploratory analysis of the individual regimens, ultraviolet therapy was associated with improved OS (HR, 0.21; P = .034) and PFS (HR, 0.26; P = .002) compared with no maintenance. CONCLUSION: Among the patients with CTCL who had received TSEB therapy, maintenance therapy improved PFS for all patients, and ultraviolet-based maintenance improved both PFS and OS in a subset of patients.
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Linfoma Cutáneo de Células T/radioterapia , Neoplasias Cutáneas/radioterapia , Piel/efectos de la radiación , Terapia Ultravioleta/métodos , Irradiación Corporal Total/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Adulto JovenRESUMEN
Patients with CTCL are at increased risk for bacteremia which is a leading cause of morbidity and mortality. We assessed risk factors for and the impact of bacteremia on survival in a retrospective cohort of 188 CTCL patients at a single US academic institution treated between 1990 and 2018. With a median follow up of 6.2 years, 20% of patients (n = 36) developed 79 bacteremia events. Risk factors for bacteremia included advanced stage, female gender, African American (AA) race, invasive lines, and chemotherapy. Bacteremia was associated with an increased risk of death on univariate and multivariable models. Bacteremia is associated with an increased risk of death in patients with CTCL. The greatest avoidable risk factors included chemotherapy treatment and presence of an invasive line. Key points 20% of patients developed bacteremia at any point in time in this analysis. Bacteremia is associated with an increased risk of death in patients with CTCL Risk factors for bacteremia include advanced stage, female gender, AA race, invasive line, and chemotherapy.
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Bacteriemia , Linfoma Cutáneo de Células T , Micosis Fungoide , Neoplasias Cutáneas , Bacteriemia/epidemiología , Bacteriemia/etiología , Femenino , Humanos , Linfoma Cutáneo de Células T/complicaciones , Linfoma Cutáneo de Células T/epidemiología , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with inferior prognosis compared with their B cell counterparts characterized by frequent relapses, resulting in a median 5-year survival of approximately 30%. Their diverse clinicopathologic features challenge existing treatment paradigms that treat all patients uniformly. Here we review recent advances in the treatment of these diseases. RECENT FINDINGS: While current treatment still relies largely on combination chemotherapy, the introduction of more effective novel and targeted therapies has improved outcomes in certain subtypes. Increasing understanding of the underlying biology of PTCL has prompted further subclassification by genetic and molecular subgroups. Overall, the most significant advances in PTCL management have resulted from improved understanding and classification of the biology of PTCL. Ongoing development of subtype-specific targeted therapies will be essential to improve long-term outcomes of patients with these diseases.
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Linfoma de Células T Periférico/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Humanos , Antígeno Ki-1/análisis , Linfoma de Células T Periférico/clasificación , Linfoma de Células T Periférico/patología , Recurrencia , Trasplante AutólogoRESUMEN
Classical Hodgkin lymphoma (cHL) in older adults is associated with inferior outcomes and increased toxicity compared to younger patients. Novel therapies like brentuximab vedotin (BV) have yielded promising results, yet their optimal use in older cHL remains unclear. We performed a systematic review to assess outcomes and toxicity associated with frontline regimens in older cHL. We screened 196 references involving chemotherapy without BV and 662 references containing BV and included 9 studies (12 arms) without BV and 6 studies (7 arms) with BV. Progression-free survival (PFS) ranged from 47 to 84% at 2 years in BV-containing arms and 42-79% at 5 years in non-BV containing trials. Pulmonary toxicity was more common in arms receiving >2 cycles of bleomycin, whereas peripheral neuropathy was associated with cumulative BV dose. This review summarizes available treatment outcomes in newly diagnosed older cHL patients and may aid clinicians in decision-making regarding available frontline approaches.Key PointsThis systematic review suggests that >2 cycles of bleomycin is associated with excess pulmonary toxicity in cHL patients older than 60 years of age.Peripheral neuropathy was more frequent in patients receiving BV-containing regimens and was associated with cumulative BV dose.BV-containing regimens are associated with high response rates in advanced-stage patients, but follow-up is limited.