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Adalimumab (ADL, Humira®, reference product), an anti-TNF-α biologic, has transformed the treatment of chronic, immune-mediated inflammatory diseases. However, the high cost of ADL therapy has driven the development of more affordable ADL biosimilars, agents with no clinically meaningful differences from the reference product. This review summarizes the product attributes of reference ADL and the nine ADL biosimilars approved and available in the USA in relation to patient experience of injection-site pain (ISP). Product formulation, delivery volume and device features (e.g., type and needle gauge size) influence patient experience of ISP with potential clinical consequences. Citrate-free formulations generally cause less ISP; injection volumes of > 1.5 ml may be associated with increased ISP. Reference ADL and all ADL biosimilars offer a citrate-free formulation, and reference ADL and four ADL biosimilars offer a high-concentration solution that allows a smaller injection volume. All available ADL products are injected subcutaneously using either a pre-filled pen (PFP) or pre-filled syringe (PFS). Patients prefer the PFP, but the PFS permits better control over the speed and duration of injection. Smaller (29-gauge) needle outer diameter is associated with less ISP; reference ADL and seven ADL biosimilars offer a device with a 29-gauge needle. In the USA, an approved biosimilar can be designated "interchangeable," allowing pharmacy-level substitution, where state law permits. In the USA, two ADL biosimilars have received interchangeability designation; others are seeking interchangeability designation from the Food and Drug Administration (n = 2), are being evaluated in clinical studies to support interchangeability (n = 2), or do not have/are not seeking interchangeability designation (n = 3). Product-related attributes influence patient experience of ISP caused by subcutaneous ADL injection. Reference ADL and ADL biosimilar products differ in their attributes, so discussion with patients about treatment options is essential to optimize adherence and outcomes.
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Adalimumab , Biosimilares Farmacéuticos , Biosimilares Farmacéuticos/uso terapéutico , Humanos , Inyecciones Subcutáneas , Reacción en el Punto de InyecciónRESUMEN
PURPOSE: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS: We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION: In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/mortalidad , Masculino , Adulto , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Pronóstico , Supervivencia sin Progresión , Estadificación de NeoplasiasAsunto(s)
Primeros Auxilios , Investigación en Educación de Enfermería , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Agricultores/psicología , Trastornos de Estrés por Calor/prevención & control , Trastornos de Estrés por Calor/enfermería , Bachillerato en Enfermería , Investigación en Evaluación de Enfermería , Enfermedades de los Trabajadores Agrícolas/prevención & control , Enfermedades de los Trabajadores Agrícolas/enfermeríaRESUMEN
Micro-credentials (MCs) and digital badges (DBs) have gained popularity in recent years as a means to supplement traditional degrees and certifications. MCs and DBs can play a significant role in supporting student-centered learning by offering personalized and flexible learning pathways, emphasizing real-world relevance and practical skills, and fostering a culture of continuous learning and growth. However, barriers currently exist within health professions education, including pharmacy education, that could limit the full adoption and implementation of MCs and DBs. Research on the use of MCs and DBs in Doctor of Pharmacy degree programs is sparse. In this integrative review, literature on the use of MCs and DBs in health professions education is reviewed, and perspectives on the benefits, issues, and potential future uses within Doctor of Pharmacy degree programs are presented.
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Educación en Farmacia , Servicios Farmacéuticos , Farmacia , Humanos , Aprendizaje , CurriculumRESUMEN
Splenomegaly is a hallmark of myelofibrosis, a debilitating haematological malignancy for which the only curative option is allogeneic haematopoietic cell transplantation (HCT). Considerable splenic enlargement might be associated with a higher risk of delayed engraftment and graft failure, increased non-relapse mortality, and worse overall survival after HCT as compared with patients without significantly enlarged splenomegaly. Currently, there are no standardised guidelines to assist transplantation physicians in deciding optimal management of splenomegaly before HCT. Therefore, the aim of this Position Paper is to offer a shared position statement on this issue. An international group of haematologists, transplantation physicians, gastroenterologists, surgeons, radiotherapists, and radiologists with experience in the treatment of myelofibrosis contributed to this Position Paper. The key issues addressed by this group included the assessment, prevalence, and clinical significance of splenomegaly, and the need for a therapeutic intervention before HCT for the control of splenomegaly. Specific scenarios, including splanchnic vein thrombosis and COVID-19, are also discussed. All patients with myelofibrosis must have their spleen size assessed before allogeneic HCT. Myelofibrosis patients with splenomegaly measuring 5 cm and larger, particularly when exceeding 15 cm below the left costal margin, or with splenomegaly-related symptoms, could benefit from treatment with the aim of reducing the spleen size before HCT. In the absence of, or loss of, response, patients with increasing spleen size should be evaluated for second-line options, depending on availability, patient fitness, and centre experience. Splanchnic vein thrombosis is not an absolute contraindication for HCT, but a multidisciplinary approach is warranted. Finally, prevention and treatment of COVID-19 should adhere to standard recommendations for immunocompromised patients.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Mielofibrosis Primaria , Trombosis , Humanos , Esplenomegalia/etiología , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/terapia , COVID-19/complicaciones , Leucemia Mieloide Aguda/terapia , Trombosis/complicaciones , Acondicionamiento PretrasplanteRESUMEN
Plasmodium knowlesi poses a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied in Macaca mulatta (rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon of Plasmodium antigenic variation was first recognized during rhesus monkey infections. Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost after P. knowlesi is passaged in splenectomized rhesus. Here we present data from longitudinal P. knowlesi infections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients with P. knowlesi malarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely via SICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed by Plasmodium falciparum.
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Malaria , Plasmodium knowlesi , Plasmodium , Aglutinación , Animales , Antígenos , Membrana Eritrocítica , Eritrocitos/parasitología , Macaca mulatta , Malaria/parasitología , Plasmodium knowlesi/genética , EsquizontesRESUMEN
BACKGROUND: Only a fraction of pediatric trauma patients are treated in pediatric-specific facilities, leaving the remaining to be seen in centers that must decide to admit the patient to a pediatric or adult unit. Thus, there may be inconsistencies in pediatric trauma admission practices among trauma centers. OBJECTIVE: Describe current practices in admission decision making for pediatric patients. METHODS: An email survey was distributed to members of three professional organizations: The American Association for the Surgery of Trauma, Society of Trauma Nurses, and Pediatric Trauma Society. The survey contained questions regarding pediatric age cutoffs, institutional placement decisions, and scenario-based assessments to determine mitigating placement factors. RESULTS: There were 313 survey responses representing freestanding children's hospitals (114, 36.4%); children's hospitals within general hospitals (107, 34.2%), and adult centers (not a children's hospital; 90, 28.8%). The mean age cutoff for pediatric admission was 16.6 years. The most reported cutoff ages were 18 years (77, 25.6%) and 15 years (76, 25.2%). The most common rationales for the age cutoffs were "institutional experience/tradition" (139, 44.4%) and "physician preference" (89, 28.4%). CONCLUSION: There was no single widely accepted age cutoff that distinguished pediatric from adult trauma patients for admission placement. There was significant variability between and within the types of facilities, with noted ambiguity in the definition of a "pediatric" patient. Thresholds appear to be based primarily on subjective criteria such as traditions or preferences rather than scientific data. Institutions should strive for objective, evidence-based policies for determining the appropriate placement of pediatric patients.
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Hospitales Pediátricos , Centros Traumatológicos , Adolescente , Adulto , Niño , Toma de Decisiones , Hospitales Generales , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
In potentially curable cancers, long-term survival depends not only on the successful treatment of the malignancy but also on the risks associated with treatment-related toxicity, especially cardiotoxicity. Malignant lymphomas affect patients at any age, with acute and late toxicity risks that could have a severe effect on morbidity, mortality, and quality of life. Although our understanding of chemotherapy-associated and radiotherapy-associated cardiovascular disease has advanced considerably, new drugs with potential cardiotoxicity have been introduced for the treatment of lymphomas. In this Review, we summarise the mechanisms of treatment-related cardiac injury, available clinical data, and protocols for optimising cardioprotection in lymphomas. We discuss ongoing research strategies to advance our knowledge of the molecular basis of drug-induced and radiation-induced toxicity. Additionally, we emphasise the potential for personalised follow-up and early detection, including the role of biomarkers and novel diagnostic tests, highlighting the role of the cardio-oncology team.
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Antineoplásicos , Linfoma , Neoplasias , Antineoplásicos/efectos adversos , Cardiotoxicidad/complicaciones , Cardiotoxicidad/diagnóstico , Cardiotoxicidad/prevención & control , Humanos , Linfoma/tratamiento farmacológico , Neoplasias/terapia , Calidad de VidaRESUMEN
Deep inspiration breath-hold, butterfly volumetric modulated arc therapy and daily imaging techniques for mediastinal lymphoma patients have been introduced in a single department. Whilst introducing these techniques, there were many practical lessons to be learned across the patient pathway, from pre-treatment through to treatment delivery.Therapeutic radiographers were key members of the multi-disciplinary team implementing these techniques. This work reflects on the experience of introducing these advanced techniques for mediastinal lymphoma patients and the lessons learnt.
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Deep inspiration breath-hold (DIBH) is an advanced radiotherapy technique that has been shown to have dosimetric benefits in the treatment of patients with mediastinal lymphoma. Whilst there is much published data on the use of DIBH in breast radiotherapy, reports on the use of the technique in mediastinal lymphoma patients remain limited. As the first NHS centre in the UK to implement DIBH in this pt group, we have evaluated our experience and success in using this technique over a 5 year period.
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BACKGROUND: Kra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype. METHODS: Kra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections during acute and chronic infections. RESULTS: As expected, the kra monkeys controlled acute infections and remained with low-level, persistent parasitaemias without anti-malarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopenia, and moderate to severe anaemia. Mathematical modelling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low. CONCLUSIONS: Kra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.
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Resistencia a la Enfermedad , Macaca fascicularis , Malaria/veterinaria , Enfermedades de los Monos/parasitología , Parasitemia/veterinaria , Plasmodium knowlesi/fisiología , Animales , Estudios Longitudinales , Malaria/parasitología , Masculino , Parasitemia/parasitologíaRESUMEN
This status article describes current state-of-the-art radiotherapy for lymphomas and new emerging techniques. Current state-of-the-art radiotherapy is sophisticated, individualised, CT-based, intensity-modulated treatment, using PET/CT to define the target. The concept of involved site radiotherapy should be used, delineating the target using the exact same principles as for solid tumours. The optimal treatment delivery includes motion management and online treatment verification systems, which reduce intra- and interfractional anatomical variation. Emerging radiotherapy techniques in lymphomas include adaptive radiotherapy in MR- and CT-based treatment systems and proton therapy. The next generation linear accelerators have the capability to deliver adaptive treatment and allow relatively quick online adaptation to the daily variations of the anatomy. The computer systems use machine leaning to facilitate rapid automatic contouring of the target and organs-at-risk. Moreover, emerging MR-based planning and treatment facilities allow target definition directly from MR scans and allow intra-fractional tracking of structures recognisable on MR. Proton facilities are now being widely implemented. The benefits of proton therapy are due to the physical properties of protons, which in many cases allow sparing of normal tissue. The variety of techniques in modern radiotherapy means that the radiation oncologist must be able to choose the right technique for each patient. The choice is mainly based on experience and standard protocols, but new systems calculating risks for the patients with a specific treatment plan and also systems integrating clinical factors and risk factors into the planning process itself are emerging.
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Linfoma/diagnóstico por imagen , Linfoma/radioterapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Conformacional/métodos , HumanosRESUMEN
BACKGROUND: Oseltamivir is frequently administered to critically ill patients with presumed influenza. It may modulate Na+, K+, and Ca2+ channels to produce bradycardia. OBJECTIVE: To evaluate the association between oseltamivir and bradycardia in critically ill patients and assess parameters associated with bradycardia. METHODS: This was a retrospective audit of 203 critically ill adults with presumed influenza receiving at least 2 doses of oseltamivir. The primary outcome was the occurrence of bradycardia, defined as a heart rate (HR) ≤59 beats per minute (BPM) while receiving oseltamivir or a decrease of ≥20 BPM compared with the lowest HR before initiating oseltamivir. RESULTS: A total of 88 (43.4%) patients manifested bradycardia, 59 with HR ≤59 BPM, 19 with HR decrease of ≥20 BPM, and 10 with both. The time from first dose to bradycardia was 51.4 ± 43 hours. In all, 48 (54.6%) patients received therapies for bradycardia, including increased inotropic/vasopressor dose, electrolyte replacement, electrocardiogram, discontinuation of other medications, cardiology consult, discontinuation of oseltamivir, and pacer placement. There were no significant differences between groups with bradycardia versus without in terms of demographics, laboratory values, hospital characteristics, or oseltamivir dosing. Multivariate logistic regression showed that bradycardia was associated with baseline HR, age, past medical history of neurological issues, and positive influenza status. Between hours 6 through 126, significant differences existed between groups in actual and lowest HR. CONCLUSION AND RELEVANCE: Oseltamivir was associated with clinically relevant bradycardia in critically ill patients. Clinicians should closely monitor HR in critically ill patients receiving oseltamivir.
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Gripe Humana , Oseltamivir , Adulto , Antivirales/efectos adversos , Bradicardia/inducido químicamente , Bradicardia/diagnóstico , Enfermedad Crítica , Humanos , Gripe Humana/tratamiento farmacológico , Oseltamivir/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND Lymphoplasmacytic lymphoma (LPL) is a mature B cell lymphoma that mostly involves the bone marrow, spleen, and lymph nodes. Involvement of extramedullary sites is very rare and has not been reported as the primary site before. CASE REPORT A 47-year-old man presented with reflux symptoms. Gastroscopy revealed a 1.5-cm gastroesophageal junction (GEJ) polyp and oesophageal ulcer. A biopsy was performed and histopathology showed active chronic inflammation with focal intestinal metaplasia and reactive epithelial changes. A CT abdomen showed eccentric thickening of the lower oesophagus and GEJ, with periesophageal, gastro-hepatic ligament, and coeliac lymph node (LN) enlargement. A laparoscopic biopsy showed no peritoneal disease. EUS showed a large ulcerated lesion in the GEJ and proximal stomach. Both were biopsied, showing squamous-columnar mucosa with edema and a population of plasma cells, small lymphocytes, and histiocytes. These expressed CD20, PAX5, CD79a, IgM, and were lambda light chain-restricted. Lymphocytes were negative for CD3, IgG, IgA, and IgD. The MIB-1 index was low. LPL was diagnosed. PET showed an increased uptake of the gastric cardia and GEJ. LNs were not metabolically active. Bone marrow was negative. Evaluation of MYD 88 mutational status failed. Serum immunofixation showed no paraprotein. These results led to a diagnosis of primary isolated LPL of the stomach. CONCLUSIONS Primary lymphoplasmacytic lymphoma may present as an isolated gastric tumor. This can be unassociated with a paraprotein in serum and increased lymphocyte/plasma cell populations within the bone marrow. Gastric LPL is rare. Physicians and pathologists need to be aware of this rare presentation.
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Neoplasias Gástricas/patología , Macroglobulinemia de Waldenström/patología , Unión Esofagogástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/radioterapia , Macroglobulinemia de Waldenström/radioterapiaRESUMEN
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.
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Enfermedad de Hodgkin/patología , Adulto , Anciano , Terapia Combinada/efectos adversos , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Humanos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/epidemiología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: We previously reported that â¼30% of patients with localized follicular lymphoma (FL) staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.