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Ocular manifestations in chronic lymphocytic leukemia (CLL) have been reported in 30% to 40% of patients and may be a result of direct tissue infiltration, concomitant blood dyscrasias, or a result of therapeutic intervention. Leukemia cutis, defined as infiltration of the epidermis or dermis by neoplastic lymphocytes, is rare. Herein, we present a case report of a patient with leukemia who presented with periorbital edema and ecchymosis. This is the first known case to date of periorbital CLL successfully treated with low-dose radiation therapy (4 Gy in 2 fractions). Clinicians should be aware of the possibility of ocular involvement from CLL, given the importance of prompt diagnosis and treatment., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Introduction: Ear involvement by non-Hodgkin lymphoma is quite rare and can be mistaken for other common lesions encountered in otolaryngology. The literature on this subject is also limited., Case Summary: A 45-year-old man with bilateral ear nodules that progressed over two years. Biopsy of the right ear revealed a B-cell small lymphocytic lymphoma (SLL). The patient responded to radiotherapy well. He received an additional dose two months after the initial treatment because of a remaining nodularity on the right earlobe. After several months, he presented a new lesion on his nasal tip, for which a biopsy confirmed a lymphoma relapse. The patient was managed with oral prednisone and low-dose radiation with a favourable response., Discussion: This case highlights the importance of including lymphoma in the differential diagnosis of ear lesions from an otolaryngology perspective. A biopsy of any lesion or nodule with an atypical course should be considered for appropriate diagnosis and management., (Copyright © 2019. Published by Elsevier Masson SAS.)

Venous thromboembolism (VTE) is associated with inferior survival in cancer patients. The risk of VTE and its effect on survival in chronic lymphocytic leukemia (CLL) patients remains unclear. The present study investigated the impact of patient-related factors, CLL prognostic markers, and CLL treatment on the risk of VTE and assessed overall survival relative to VTE. All patients in the Danish National CLL Registry (2008-2015) were followed from the date of CLL diagnosis to death, VTE, emigration, or administrative censoring. Hazard ratios (HRs) were estimated using Cox models, and second primary cancers and anticoagulation treatment were included as time-varying exposures. During a median follow-up of 2.6 years, 92 VTEs occurred among 3609 CLL patients, corresponding to a total incidence rate of 8.2 VTEs per 1000 person-years (95% confidence interval [CI], 6.7-10.1). A history of VTE or second primary cancer was associated with HRs of VTE of 5.09 (95% CI, 2.82-9.17) and 3.72 (95% CI, 2.15-6.34), respectively, while β 2 -microglobulin >4 mg/L, unmutated immunoglobulin HV and unfavorable cytogenetics had lower HRs. CLL patients with VTE had marginally higher mortality, which was most pronounced among patients <60 years of age (HR, 7.74; 95% CI, 2.12-28.29). Our findings suggest that markers of unfavorable CLL prognosis contribute to an increased risk of VTE; however, previous VTE or a second primary cancer is more strongly associated with the risk of VTE than any CLL-specific marker. Focusing attention on this preventable complication may improve survival in young CLL patients., (© 2018 by The American Society of Hematology.)

Background: Cytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic., Case Presentation: A 65 year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases. Within hours of each weekly dose of RT, he experienced fever, tachycardia, hypotension, rash, dyspnea, and rigors. Based on clinical suspicion for CRS, blood cytokine measurements were performed 1 h after the second and third dose of RT and demonstrated tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels approximately ten-fold higher than normal. These were near normal immediately prior to the third dose of RT, and resolved to normal levels 3 weeks after RT. He experienced rapid regression of irradiated tumors, with development of new sites of metastases soon thereafter. A literature review revealed no clinical cases of CRS after RT for cancer., Conclusions: RT during anti-PD1 immunotherapy in a patient with underlying immune dysfunction appeared to be the putative mediator of an immune process which yielded significant increases in pro-inflammatory cytokines, and produced the clinical symptoms meeting the definition of grade 3 CRS. This case demonstrates the capability of RT to elicit immune-related adverse events.

Background: The goal of this study was to assess the survival differences seen in early-stage and advanced-stage nodular lymphocytic predominant Hodgkin lymphoma (NLPHL) based on treatment modality., Patients and Methods: The National Cancer Database was queried to identify patients diagnosed with NLPHL between 2004 and 2012. Overall survival (OS) was determined using univariate and multivariate Cox regression analysis. Kaplan-Meier and log-rank analysis were used to estimate differences in OS between treatment groups., Results: A total of 1968 patients were identified for analysis, consisting of stage I (40.4%), stage II (29.3%), stage III (22.3%), and stage IV (8.0%) disease. The median age of patients was 46 years. The following factors were predictive of radiotherapy (RT) omission in treatment: increasing age, black race, Medicare insurance, chemotherapy use, stage II to IV disease, and the presence of B-symptoms. On survival analysis, RT was associated with prolonged OS in all stages of NLPHL (50.1 vs. 42.4 months; P < .01). The OS benefit of RT persisted on multivariate analysis (hazard ratio, 0.37; P < .01). On subset analysis, RT was associated with prolonged OS in early disease (49.8 vs. 45.5 months; P < .01), whereas a trend towards an OS benefit was observed in advanced-stage (54.1 vs. 39.6 months; P = .06) NLPHL. Radiotherapy was also associated with prolonged OS among patients with B-symptoms (49.0 vs. 42.6 months; P < .01)., Conclusion: The use of RT in NLPHL is less likely among those with advanced-stage disease and B-symptoms. However, we found RT to be associated with prolonged OS in all stages of NLPHL, including those with B-symptoms., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells., Methods: We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL. Radiosensitivity tests were performed for the index patient under Idelalisib and after the addition of Idelalisib to healthy individuals' blood. Radiosensitivity in human lymphocytes was analyzed with a three color in situ hybridization assay. Primary skin fibroblasts were studied after a treatment with Idelalisib for apoptosis, necrosis and cell cycle using flow cytometry. DNA double-strand break repair was analyzed by γH2AX immunostaining., Results: The index patient presented a strong grade 2 radiodermatitis and grade 3 mucositis after irradiation with 20 Gy and a simultaneous intake of Idelalisib. Irradiations without Idelalisib medication were well tolerated and resulted in not more than grade 1 radiodermatitis. The index patient under Idelalisib had a radiosensitivity of 0.62 B/M which is in the range of clearly radiosensitive patients. A combined treatment of lymphocytes with 2 Gy and 10 nmol/l Idelalisib showed a tendency to an increased radiosensitivity. We found a clear increase of apoptosis as a result of the combined treatment in the Idelalisib dose range of 1 to 100 nmol/l compared to solely irradiated cells or solely Idelalisib treated cells (p = 0.05)., Conclusion: A combined Idelalisib radiotherapy treatment has an increased risk of side effects. However, combined therapy seems to be feasible when patients are monitored closely.

Primitive lymphomas of the bone are exceptional tumors, representing 4% of all non-Hodgkin lymphomas. The location at the skull remains the rarest. We report the case of a 56 year old patient with lytic lesions in the skull of a small cell lymphoma B, treated with primary chemotherapy and intensity-modulated radiotherapy in arctherapy with a dose of 30Gy in 15 fractions. With a follow-up time of 18 months after the end of treatment, the patient has no sign of disease evolution., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Chronic lymphocytic leukaemia is a common disease affecting the hematopoietic organs. The disease remains classically indolent for years preceding a blast crisis. However, the disease can affect all parts of the body. We report here an unusual localization., Case Presentation: A 72-year-old man was followed for 2 years for an indolent chronic lymphocytic leukaemia while he presented a rapidly progressive dysuria. Prostate biopsies were performed concluding to a prostate involvement by the chronic lymphocytic leukaemia. In the absence of progression according to RAI staging system and Binet's classification, he was treated with local low-dose radiotherapy, twice 2 Gy, allowing for a rapid resolution of the symptoms. No systemic treatment was introduced, and 1 year after the completion of his treatment, he is still under watchful waiting strategy for his chronic lymphocytic leukaemia., Conclusion: Low-dose radiotherapy is an underused effective strategy in indolent lymphoma. In this case, urinary symptoms from a prostate involvement were relieved non-invasively at low cost., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: Chronic lymphocytic leukaemia (CLL) is a common haematological malignancy that mainly occurs in the elderly population. Patients frequently have comorbidities compromising the use of old and new systemic therapies., Methods and Results: We report the prevalence of comorbidities in patients with CLL as present in the southern region of the Netherlands Cancer Registry. Comorbid conditions were present in 67% of the male and 63% of the female patients, and became more common with increasing age. Furthermore, we describe the beneficial local and abscopal effects of splenic irradiation in four patients with CLL who were not suitable for systemic chemoimmunotherapy because of severe comorbidities, or who were unwilling to undergo systemic therapy., Conclusion: Our results show that, although an old tool, splenic irradiation should not be forgotten as a potentially effective palliative treatment option in frail patients with symptomatic CLL.

Despite initial responses to chemoimmunotherapy, relapse and minimal residual disease (MRD) remain major issues in treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients. We administered (131)I-tositumomab to patients in complete response (CR) or partial response (PR) after induction chemotherapy. Toxicities and rate of PR to CR conversion and MRD elimination were assessed three months later. The study stopped prematurely after enrolling 16 patients. Four (25%) were in CR, 12 (75%) in PR, and 12 (75%) had MRD. Three months after treatment with (131)I-tositumomab, CR was achieved (n = 8; 50%) or sustained (n = 4; 25%) in 12 patients and MRD was eliminated in four of 12 patients (33%). Hematologic toxicities were anemia in one patient (6%), neutropenia in 13 (81%), and thrombocytopenia in eight (50%). Two patients (12%) developed MDS 17 and 20 months after consolidation. Consolidation with (131)I-tositumomab for CLL/SLL patients in first remission is feasible and may provide the benefit of converting PR to CR and/or eliminating MRD.