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Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.
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The most common non-Hodgkin's lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL), an aggressive lymphoma that can be cured with standard frontline chemo-immunotherapy in 60%-70% of patients but with historically poor outcomes for relapsed/refractory disease. Patients with relapsed DLBCL after autologous stem cell transplant (ASCT) or with chemotherapy-refractory disease have a particularly dismal prognosis, with a median overall survival (OS) of only 6 months. Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma, with multiple FDA approved CAR T products now commercially available in many developed world including European countries. Ongoing studies seek to move CAR T cells to earlier lines of therapy and to characterise the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukaemias. Other areas of active research address CAR T in combination with other lymphoma-directed therapies, and mechanisms of CAR T resistance. We conducted a retrospective observational study assessing the outcomes of patients referred to our tertiary centre, University College London hospital NHS foundation Trust (UCLH) from January 2018 to December 2022, over a 48-month period. We collected data including patients' demographics, types of lymphomas, prior lines of therapies including stem cell transplantation, bridging therapies as appropriate, complications and overall response rate. We also analysed the communication between teams during the challenging period of the COVID-19 pandemic.
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Introduction: Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of infection. CLL is associated with a secondary immunodeficiency and impaired response to vaccination. Recent British Society of Haematology guidelines recommend that patients with CLL should receive vaccination against pneumococcal infection at diagnosis, an annual influenza vaccine and COVID-19 vaccination. Patients aged 70-79 years should also receive the Shingrix vaccine. Patients with CLL should not receive live vaccines. In response to this guideline, a letter detailing vaccination requirements was created for patients to give to their general practitioner (GP). The local process for vaccination referral has since changed. Previously, vaccination requirements were communicated to the GP via letter. There is now a dedicated Vaccination Hub to which clinicians can directly refer patients for appropriate vaccinations. Aim(s): The aim of this project was to assess vaccination referral and vaccination status in patients with newly diagnosed CLL. Method(s): All new diagnoses of CLL from 2021 to 2022 were identified by review of the Haematology Multi-Disciplinary Team meeting electronic registration forms. Electronic patient records were reviewed to determine vaccination referral completion and vaccination status. Result(s): A total of 29 patients were identified as new diagnoses of CLL. Seventeen patients were diagnosed in 2021 and 12 in 2022. Sixty-nine percent of the patients were male and the average age was 70.9 years. Vaccination was discussed with 11 patients (38%) and 10 patients (34%) were referred for vaccination. Eleven patients (38%) had never received a pneumococcal vaccine. Nine patients (31%) had previously received the vaccine but not within the past 5 years. Five patients (17%) patients had received one dose of Pneumovax 23 following referral. No patients had received the initial Prevenar 13 vaccine. Twelve patients (41%) had not received an influenza vaccine. Of those who had received the vaccine, the majority (70%) had received this routinely. Similarly, 71% of patients had received the COVID-19 vaccine routinely as opposed to three patients who received this postreferral. Of those who were eligible, 50% had received the Shingrix vaccine. Conclusion/Discussion: Local rates of vaccination in patients with CLL are low. Numbers were too small to allow for comparison between the methods of referral. Of those referred, not all received the appropriate vaccinations. Further work is therefore required to improve both the number and completion of the referrals. Future steps will include local teaching on vaccinations in CLL and the referral pathway.
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Introduction: Bruton's tyrosine kinase inhibitors (BTKi) are used extensively within the NHS to treat specific B-cell malignancies with patients stopping BTKi usually due to adverse events or disease progression. The objective of this study was to analyse effectiveness of BTKi therapy for chronic lymphocytic leukaemia (CLL) at our centre compared to previously published real-world data from the UKCLL Forum (Follows et al, Blood 2019). In addition, we investigated treatment-related adverse events (AE) and second malignancies. Method(s): This is a single-centre retrospective study of 112 CLL patients treated with a BTKi for a minimum of 4 weeks between 2014 and 2022 (ibrutinib n = 71, acalabrutinib n = 38, zanubrutinib n = 3). Treatment was first line (n = 39), second line (n = 44) and 3+ line (n = 29). Patient demographics, duration of BTKi therapy, Aes, discontinuation reasons and second malignancies were collected. Aes were compared with a parallel cohort of 53 non-CLL BTKi-treated patients. Result(s): Median age starting treatment was 73 years, and 71% were male. Primary outcomes were discontinuation-free survival (DFS) and overall survival (OS). With a median follow-up of 3.90 years, the median DFS was 4.18 years (95% CI: 3.52-4.91) with a median OS of 6.35 years (95% CI: 5.52-NA). These compare favourably with previous UKCLL forum data (median DFS = 2.79 years;median OS = 4.66 years), although our patients were more likely to receive BTKi earlier in treatment (3rd line or beyond: 26% of our patients vs. 78% in the UKCLL Forum). The most common Aes included bleeding, cytopenia, infection, cardiac events and mouth ulcers, with 21% stopping BTKi for CLL due to Aes whilst 15% of non-CLL BTKi patients stopped due to an AE. Second malignancies were reported in 49% of CLL patients, yet only 34% of non-CLL patients. Among patients with a confirmed cause of death, infection was the most common cause (39%), followed by CLL (33%), then second malignancy (18%). Of the 31 deaths in 2020 and 2021, 7/31 (23%) were due to, or in association with COVID-19 infection. No COVID-19 deaths were associated with BTKi in non-CLL patients. Conclusion(s): We demonstrate a favourable real-world DFS and OS for BTKi-treated CLL patients although a high number of patients still stop BTKi due to Aes. The very high incidence of second malignancies for all BTKi-treated patients and COVID-19 and infection-related deaths for CLL patients is concerning. As CLL is known to associate with high levels of second cancers, it remains unclear whether BTKi use increases this risk further.
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The aim of the work is to form the principles of a personalized approach to the management of patients with COVID-19 with a complicated comorbid background. Material and methods. The article describes a clinical case of successful recovery of an 87-year-old patient from a new coronavirus infection COVID-19, complicated by pneumonia involving 36% of the lung parenchyma area. Along with age, the situation was aggravated by the comorbid status of the patient: the presence of chronic lymphocytic leukemia, hypertension, mechanical prostheses of the mitral and aortic valves, postinfarction cardiosclerosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus, stage 4 CKD, anemic syndrome, and subclinical hypothyroidism. Results. The C-reactive protein level at admission was 114.46 mg/L. The patient refused hospitalization. Baricitinib 4 mg, favipiravir according to the scheme, vitamin D 2000 units were prescribed for the previously taken therapy. Already after 3 days, C-reactive protein decreased by 4.6 times, and by the 8th day by 15.5 times and amounted to 7.38 mg/ml. The temperature returned to normal on day 2 from the start of baricitinib. In dynamics, a decrease in creatinine level to 177.0 mumol/l was noted, the glomerular filtration rate increased to 30 ml/min/1.73 m2, which corresponded to stage 3b of CKD (a pronounced decrease in glomerular filtration rate). Conclusion. Despite the age of the patient, many comorbidities, each of which could be fatal, the timely use of baricitinib on an outpatient basis made it possible to stop the progressive course of the disease.Copyright © Eco-Vector, 2023. All rights reserved.
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Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative option for patients with hematologic diseases. When considered candidates, patients face barriers to receive a transplant. Therefore, we aimed to analyze factors that limit or favor access to an alloHSCT in a population that has been HLA typed and therefore with a potential intent-to-transplant. Method(s): We retrospectively reviewed records from 2015 until the start of the COVID19 pandemic in two Mexican government- funded transplant centers and one private that have in-house HLA typing;in two of them, an outpatient transplant strategy is followed for most patients. HLA-typed patients who were potentially eligible for transplantation were included and their outcomes were assessed in an intent-to-transplant basis. We compared the outcomes of patients who underwent transplantation to those who did not and evaluated contributing barriers to access alloHSCT with multivariate logistic regression. Result(s): A total of n=374 patients were analyzed. The median age at HLA-typing was 35 years (IQR 23-47);59.3% had acute(Table Presented) leukemia, 17.4% bone marrow failure or myelodysplastic neoplasms, 13.1% lymphoma, 8% myeloproliferative neoplasms, 1.1% chronic lymphocytic leukemia and 1.1% multiple myeloma. Most patients (55.9%) had government insurance coverage. Median time from diagnosis to HLA-typing was 8 months (IQR 3-19). The majority had a potential donor (94.4%): 56.4% haploidentical, 37.4% a matched sibling donor and 0.5% an unrelated donor. Almost half of them received a transplant (n=185, 49.5%), the median time from HLA-typing to alloHSCT was 2 months (IQR 1-5.5). Disease activity or progression was the biggest barrier for transplantation;Table 1. Donor availability limited transplant access for 12.1% of patients. Access to transplantation was favored by private/out-of-pocket payment (OR 2.1 95% CI 1.3-3.4), and receiving care in the outpatient center (OR 6.4 95% CI 4-10.0), while HLA matching was not (OR 1.2 95% CI 0.8-1.8). Non-relapse mortality in alloHSCT was 21%. Median overall survival (OS) from the intent-to-transplant cohort was 16 months (CI 95% 12.4-19.6). An OS landmark analysis for patients alive at or beyond 2 months (the median time from HLA-typing to alloHSCT) showed prolonged survival in alloHSCT (30 vs 12 months, p <.001), Figure 1. By the time of the analysis 159 patients (42.5%) were still alive and 115 (30.7%) were event-free.(Figure Presented)Conclusion: The most frequent barrier to transplantation was the disease itself, followed by the transplant waitlist and comorbidities. Access to resources and an outpatient strategy or "center effect" favored alloHSCT. In the era of haploidentical transplantation, donor availability was a smaller issue. Efforts to improve timely referrals and access to effective pre-transplant therapies should be undertaken.Copyright © 2023 American Society for Transplantation and Cellular Therapy
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Background: Previous studies had demonstrated that patients with hematologic malignancies had suboptimal antibody response after receiving COVID-19 vaccines, especially among those having previously treated with anti- CD20 monoclonal antibodies. Method(s): Adult patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL) were enrolled before receiving the second dose of SARS-CoV-2 vaccine. Determinations of anti-SARS-CoV-2 spike and nucleocapsid IgG titers were performed every 1-3 months, after they received the second and the third dose of SARS-CoV-2 vaccine, respectively. Patients were excluded from analysis if they were diagnosed with COVID-19. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from subsequent analyses. Result(s): A total of 85 participants were enrolled, including 42 (49.4%) with diffused large B-cell lymphoma, and 13 (15.3) with follicular lymphoma and 9 with CLL. 72 (84.7%) participants had received anti-CD20 monoclonal antibodies, with a median interval of 24 months between last anti-CD20 treatment and the second dose of vaccine, and 21 (24.7%) had HIV infection. Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/ mL within 12 weeks after the second dose of vaccine included HIV infection (adjusted odds ratio [aOR], 0.14;95% CI, 0.04-0.51), active hematologic disease (aOR, 5.50;95% CI 1.42-21.32), receipt of anti-CD20 monoclonal antibodies (aOR, 6.65;95% CI 1.52-29.07), and receipt of two doses of homologous mRNA vaccination (aOR, 0.17;95% CI 0.05-0.56). In the participants having previously treated with anti-CD20 regimen, only 8.6% achieved an antibody response ( >141 BAU/mL) in the first year, while 78.3% achieved anti-spike IgG titer > 141 BAU/mL after two years post B-cell depleting treatment. After the third dose of SARS-CoV-2 vaccine, 53.6% achieved an antispike IgG titer > 141 BAU/mL in the first year post anti-CD20 treatment. Conclusion(s): Our study demonstrated that previous treatment with anti-CD20 monoclonal antibodies was associated a lower antibody response among patients with lymphoproliferative disorders receiving two doses of SARS-CoV-2 vaccine. While two doses of SARS-CoV-2 vaccines might not be sufficient even one year apart from the last dose of rituximab, a third dose of vaccine may boost anti-spike IgG particularly in the subset of recent exposure to rituximab. Anti-spike IgG determined 1-3 months after the second (A) / third (B) dose of COVID-19 vaccine, stratified by the interval between last anti-CD20 regimen and the second / third dose of COVID-19 vaccine. (Figure Presented).
ABSTRACT
The aim of the work is to form the principles of a personalized approach to the management of patients with COVID-19 with a complicated comorbid background. Material and methods. The article describes a clinical case of successful recovery of an 87-year-old patient from a new coronavirus infection COVID-19, complicated by pneumonia involving 36% of the lung parenchyma area. Along with age, the situation was aggravated by the comorbid status of the patient: the presence of chronic lymphocytic leukemia, hypertension, mechanical prostheses of the mitral and aortic valves, postinfarction cardiosclerosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus, stage 4 CKD, anemic syndrome, and subclinical hypothyroidism. Results. The C-reactive protein level at admission was 114.46 mg/L. The patient refused hospitalization. Baricitinib 4 mg, favipiravir according to the scheme, vitamin D 2000 units were prescribed for the previously taken therapy. Already after 3 days, C-reactive protein decreased by 4.6 times, and by the 8th day by 15.5 times and amounted to 7.38 mg/ml. The temperature returned to normal on day 2 from the start of baricitinib. In dynamics, a decrease in creatinine level to 177.0 mumol/l was noted, the glomerular filtration rate increased to 30 ml/min/1.73 m2, which corresponded to stage 3b of CKD (a pronounced decrease in glomerular filtration rate). Conclusion. Despite the age of the patient, many comorbidities, each of which could be fatal, the timely use of baricitinib on an outpatient basis made it possible to stop the progressive course of the disease.Copyright © Eco-Vector, 2023. All rights reserved.
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Introduction. Multisystem inflammatory syndrome in adults (MIS-A) is a rare but potentially life-threatening sequel of SARS-CoV-2 infection, requiring early recognition and treatment. Nevertheless, it is often hard to distinguish MIS-A from other COVID-19-related hyperinflammatory complications. Case presentation. A 74-year-old male presented to the emergency department with persistent fever, diarrhea, altered consciousness, polymorphous rash with oral lesions and erythema of the palms and soles, with progressive exfoliation. The patient had been hospitalized for COVID-19 four weeks before and was suffering from chronic lymphocytic leukemia, diabetes and hypertension. During his recent hospital stay he received multiple courses of antibiotics and was discharged home with instructions to add sitagliptin and re-initiate therapy with ibrutinib. Upon re-admission, polymerase chain reaction test for SARS-CoV-2 was still positive and inflammatory markers were markedly elevated. Although MIS-A could not be excluded, a presumptive diagnosis of Stevens-Johnson Syndrome (SJS) was made, and the patient was treated empirically with intravenous immunoglobulin and high-dose methylprednisolone. SJS is usually considered an adverse drug reaction that affects the skin and mucous membranes. In this patient, MIS-A was also initially included in the differential diagnosis due to previous COVID-19, despite the patient's advanced age and lack of cardiac involvement or conjunctivitis. The patient only partially fulfilled current diagnostic criteria for MIS-A. Conclusions. SJS results from a dysregulated immune response and can have a similar presentation to MIS-A. A better characterization of both conditions is required particularly in older adults with comorbidities, to facilitate timely diagnosis and management and to reduce mortality.Copyright © ENS Editions. Tous droits reserves pour tous pays.
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During the pandemic, a large number of works devoted to COVID infection have appeared, which have made it possible to understand the pathogenetic features of the disease and to accumulate significant clinical experience. However, the question remains about the degree of participation of humoral and cellular (primarily T-cell) immunity in the mechanisms of immune defense and resistance to COVID-19, the individual features of the immune response in different subjects. Post-COVID syndrome is currently a separate diagnosis included in the ICD-10 International Classification of Diseases, but the long-term effects of the SARS-CoV-2 on the immune system are not yet well established. At the same time, a long-term increased activity of the immune system can contribute to the development of autoimmune reactions. The review of the literature presents the results of studies, mainly devoted to immune system disorders after COVID infection. The changes in subpopulations of T-lymphocytes, B-lymphocytes, their functional properties, the complement system and other factors of humoral immunity, as well as the production of a number of cytokines are described. Data on immune disorders in post-COVID syndrome and during the convalescence period are presented in detail. Since COVID-19 is an infection that has a significant impact on the hematopoietic system and hemostasis, special attention is paid to the category of subjects with an increased risk of severe complications. Among the latter are elderly patients, persons suffering from diabetes mellitus, oncological and oncohematological patients, in particular, with hematopoietic and lymphoid tissue neoplasia, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma. The review pays special attention to the peculiarities of the course of COVID-19 and the response of the immune system to vaccination in patients with oncohematological diseases. Deciphering the significance of individual links of cellular and humoral immunity in patients who have undergone COVID-19 is an important issue in creating effective vaccines and improving therapeutic methods.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Background: In patients with hematologic malignancies response to Covid-19-vaccination is unpredictable because these patients were excluded from clinical trials in the past. Method(s): We measured B-cell-response by means of Covid-S1-antibody reaction (SARS-CoV-2 IgG, Siemens Atellica IM) at earliest 3 weeks after second vaccination with the BNT162b2. In some patients T-cell-response is determined by a Covid-Quantiferon-test (QuantiFERON SARS-CoV-2, Qiagen) Result: Untill August 2021 results for Covid-S1-antibody-testing were present in 89 patients. In 46 of these patients response to vaccination was missing by means of antibody determination (no measurable antibodies against S1-antigen). Patients with no response to vaccination were mainly patients with B-cell-lymphoma but also patients with multiple myeloma und chronic myelomonocytic leukemia. 56 of 89 patients were on or after therapy with CD20-antibodies, respectivley. 39 of these 56 Patients had no response to vaccination. Discussion(s): Most available data concerning response to vaccination against Covid-19-virus in patients with hematologic malignancies relate to chronic B-cell leukemia and Covid-S1-antibody response. We present single institution data of a variety of malignant hematologic diseases and evalutate T-cell-response additionally. Conclusion(s): Patients with hematologic malignancies and treatment with CD20-abtibodies have a very high risk not to respond to vaccination against Covid-19-virus. Since vaccination and testing has not finished yet in our patients we will present updated results on response to vaccination with respect to hematologic diagnosis, total dose of and intervall to CD20- antibody-therapy on DKK-meeting in 2022.
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Objective To report a case of Anti-Contactin-Associated Protein-like2 (CASPR-2) autoimmunity in a patient with low-grade Chronic Lymphocytic Leukemia (CLL) following COVID-19 vaccination and infection. Background Anti-CASPR2 antibody disorder has been associated with neoplastic disorders like thymoma. Recent reports enlist COVID-19 as apotential trigger of CASPR2 autoimmunity. While the clinical presentations are similar, management differs based on the underlying etiology. Design/Methods We review a case of anti-CASPR2-antibody associated disorder with concurrent low grade CLL and recent history of COVID-19 vaccination and infection. Additionally, we review the literature and discuss the therapeutic challenges. Results A 73-years old male presented with five months of progressive fatigue, weight loss, diffuse sweating, muscle cramps, and neuropathic pain. He eventually developed bilateral upper and lower facial weakness. Patient contracted a mild COVID-19 infection two months prior and COVID- 19 vaccination one month prior to his symptom onset. His exam was remarkable for bilateral facial weakness, diffuse fasciculations and sensory neuropathy on his trunk and extremities. His diagnostic work up including bone marrow biopsy was consistent with a chronic lymphocytic leukemia (CLL)-like immunophenotype. Cerebrospinal fluid (CSF) analysis was remarkable for five WBC (lymph-dominant) and protein of 74 mg/dl. Serum paraneoplastic panel revealed positive CASPR2 antibody with a titer of 1:100. Magnetic Resonance Imaging (MRI) of the brain showed enhancement of bilateral cranial nerve VII. After lack of clinical response to IV methylprednisone (1 gram for 5 days), patient was treated with a single cycle of IV immunoglobulin (IVIG). He had complete recovery of his symptoms except for residual facial weakness. He remains stable at his six months post-treatment follow-up. Conclusions Anti-CASPR2 associated autoimmunity following COVID-19 infection or in the setting of CLL has previously been reported. However, cranial neuropathy in association with CASPR2 antibody has never been. A trial of IVIG could be beneficial in patients with viral-spike protein-induced autoimmunity and CLL who do not otherwise meet the criteria for CLL treatment.
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Introduction: Central nervous system (CNS) infiltration in chronic lymphocytic leukemia (CLL) is a rare presentation of CLL that can potentially have disastrous complications. Reported prognosis is poor. The objective of this study is to report a series of cases of CLL with CNS infiltration. Method(s): This is a case-series of a Brazilian CLL registry (Registro Brasileiro de Leucemia Linfocitica Cronica). We included patients with CLL and CNS infiltration. This is a descriptive study. Result(s): A total of 10 (0.28%) in 3610 patients were identified with confirmed (80%) or suspected (20%) CNS infiltration. Median age at CLL diagnosis was 57.5 y/o (range: 50 - 76). Three (30%) patients were diagnosed with CNS infiltration concomitantly with the CLL diagnosis, while others (70%) were diagnosed at a median of 41 months of CLL diagnosis (range: 11 to 119 months). Only three (30%) patients had been previously treated for CLL. Most common symptoms of CNS infiltration were convulsion (30%), altered mental status (30%), headaches (30%), ophthalmologic (30%), and urinary incontinence (20%). Amnesia, asthenia, vomiting, hemiparesis, cervicalgia, and dizziness were also present (one patient each). Of the patients with confirmed CNS infiltration, diagnoses were performed through liquor exam (all patients) and biopsy (one patient). Of the two patients with suspected CNS infiltration, one achieved complete response and the other, partial clinical response, following instituted CLL-directed therapy with (1 patient) or without (1 patient) intrathecal chemotherapy. Of the other 8 patients, 3 achieved complete response, 2 failed treatments, 1 was not evaluated and 2 had missing information. Of all patients, 5 are alive, 3 died of sepsis, multiorgan failure following CNS methotrexate-related toxicity, and COVID, and 2 had missing information. Discussion(s): Our results show that the prognosis of CNS infiltration in CLL can be relatively good, with at least 50% of patients alive at 1 year. However, a series of 18 patients published by Strati et al has shown a poorer outcome, with half of the patients dead at 1 year. Although all patients were diagnosed by liquor exam, that same study reported a low specificity for liquor exam in CLL (42%) due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. Establishing CNS CLL as the cause of the symptoms can be difficult, since up to 70% of patients with CLL have CNS infiltration in autopsy studies, and our results may be superestimated. In summary, CNS infiltration in CLL is a rare event, and further studies are needed to address prognosis and management. Copyright © 2022
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Introduction: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with clonal proliferation of functionally incompetent mature B lymphocytes, defined by an absolute lymphocyte count>5 9 109/ml malignant cells in the blood. The disorder is more common in men. In most of the cases, it is asymptomatic and diagnosed during routine blood investigations while getting evaluated for some other disease. However, patients need treatment once they are symptomatic with painless enlarged, bulky lymphnodes, anemia or thrombocytopenia. Case report: We report a case of 67 year female, with Type-2DMand HTN, who presented with difficulty in breathing to the emergency during the first wave of Covid -19 pandemic. Chest X-ray revealed left mid zone opacity suggestive of a lung mass. CT Thorax done showed multiple mildly enlarged mediastinal lymph nodes, with lobulated heterogeneously enhancing mass in the prevascular compartment of anterior mediastinum compressing left upper lobar bronchus. USG guided core needle biopsy of left upper lobe mass was done and pleural fluid was analysed, which was suggestive of a lymphoproliferative neoplasm. Then CBC was advised which demonstrated lymphocytosis. Flow cytometry and IHC confirmed the diagnosis mature B-cell neoplasm Chronic Lymphocytic Leukemia (CLL). Discussion(s): Pulmonary manifestation of CLL include, hilar and mediastinal lymphadenopathy. Lung masses are a rare presentation. Richter's transformation is a unique complication of CLL. However, patients with CLL also have an increased risk of secondary malignancy most commonly Kaposi sarcoma, malignant melanoma and carcinoma lung. Our case is unique,as there were no features of Richter transformation that is weight loss, fever, night sweats, muscle wasting and increased hepatosplenomegaly or lymphadenopathy. She was evaluated for respiratory distress and diagnosed on Lung mass biopsy as atypical lymphoid cell infiltration and not as lung carcinoma or transformation to high grade lymphoma. Conclusion(s): Clinicians should be aware that though chronic lymphocytic leukemia is diagnosed incidentally on routine blood investigations, atypical presentation must be kept in mind. A simple CBC and a peripheral smear examination gives a clue to the diagnosis at the earliest.
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A 75-year-old man with a history of chronic ischemic heart disease with a previously normal blood count, presented to the emergency room with fever and tachycardia. There was no hepatosplenomegaly or lymphadenopathy. An electrocardiogram showed left bundle branch block. Because of the fever the patient underwent SARS-CoV-2 RNA testing with positive result. The patient's blood count showed a WBC of 10.46 x 109/L, lymphocytes 4.51 x 109/L, hemoglobin 129 g/ L, and platelet count 233 x 109/L. D-Dimer was 659 mug/L (normal range <500) and IL6 was 76.3 pg/ml (normal range <6.4). A computed tomography scan of the chest showed bilateral interstitial infiltrates associated with multiple enlarged mediastinal lymph nodes. Following a rapid and unexpected increase of the WBC to 17.49 x 109/L with lymphocyte count of 8.37 x 109/L, a blood film and immunotyping were performed. The film showed small/medium sized lymphocytes, with a variable N: C ratio and moderately basophilic cytoplasm. Smear cells were present. About 25% of the lymphocytes showed the negative images of one to three rodshaped crystals (average 2 per cell). Some immature monocytes and neutrophils showed mild toxic granulation or abnormal nuclear shapes, consistent with COVID-19. Flow cytometric immunotyping showed an increased number of circulating B cells (93% of lymphocytes, 7.78 x 109/L) with lambda light chain restriction and expressing CD19, CD5, CD23, weak CD20, CD43, and CD200;CD10, CD79b, CD81, FMC7, and CD38 were negative. At this stage the clinical picture could not be distinguished from chronic lymphocytic leukemia (CLL). Two months later the WBC and lymphocyte count returned to normal and immuno typing showed only 0.63 x 109/L CD5-positive clonal B cells. Lymphocytes with cytoplasmic crystals were still present. A diagnosis of monoclonal B-cell lymphocytosis (MBCL) was made. Patients with CLL in whom COVID-19 led to a marked but transient increase in the lymphocyte count have been reported. In our case, COVID-19 in a patient with MBCL led to an increase in the lymphocyte count simulating CLL but follow-up indicated the correct diagnosis. We report here the observation of endocellular crystals, attributable to crystallization of immunoglobulin, in MCBL, a phenomenon previously reported in CLL.
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SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Organizing pneumonia (OP) is a form of interstitial lung disease with a distinct histopathological pattern where bronchioles and alveoli become inflamed. It is associated with many clinical conditions including infections and connective tissue disease. OP has also been seen in patients with hematologic malignancies, however, primary pulmonary presentation of chronic lymphocytic leukemia (CLL) is uncommon. We present a rare case of OP as an initial presentation of CLL. CASE PRESENTATION: A 62 year-old male with a sixty pack year smoking history and COVID-19 infection one month ago presents with complaints of worsening dyspnea, headaches, productive cough, and congestion of 10 days duration. Patient is unvaccinated and did not require hospitalization for his COVID-19 infection. His vital signs on admission were significant for tachypnea with respiratory rate of 35 and hypoxia with oxygen saturation of 84% on room air. He initially required oxygen supplementation via non-rebreather mask to maintain oxygen saturation >88%. A chest tomography (CT) scan was completed and revealed bilateral dense consolidations with ground-glass opacities and air bronchograms consistent with OP. The scan was also significant for bulky mediastinal lymphadenopathy. The patient denied any personal or family history of autoimmune disease, occupational exposures, and recent travel. Evaluation for infection and for underlying connective tissue disease was unremarkable. He was started on broad spectrum antibiotics and high dose steroids. Due to fluctuating lymphocytosis, bulky lymphadenopathy, and negative infectious workup despite clinical improvement, he underwent a bronchoscopy with endobronchial ultrasound guided transbronchial needle aspiration of lymph nodes. Immunohistochemical (IHC) stains of these samples were compatible with CLL. Additionally, peripheral blood flow cytometry was also diagnostic of CLL. Oncology was consulted for further evaluation and treatment of CLL. The patient's respiratory symptoms improved and oxygen requirements decreased with steroid treatment and he was discharged home. DISCUSSION: OP occurring in patients with hematologic malignancies has multiple etiologies. Most case reports describe patients with previous exposure to chemotherapy, radiotherapy, or bone marrow transplant. However, our patient had no such exposure history and no prior diagnosis of a hematologic malignancy. Infectious and autoimmune etiology were considered, but serologic evaluation was unremarkable. Flow cytometric analysis of lymph node tissue along with lymphocytic bronchoalveolar lavage was consistent with initial diagnosis of CLL. CONCLUSIONS: Despite the low incidence, hematologic malignancy should be considered as a differential diagnosis in all patients who present with organizing pneumonia. Prednisone therapy for 6-12 month duration has been shown to reduce respiratory symptoms and may improve survival. Reference #1: Craig E. Daniels, Jeffrey L. Myers, James P. Utz, Svetomir N. Markovic, Jay H. Ryu. Organizing pneumonia in patients with hematologic malignancies: A steroid-responsive lesion. Respiratory Medicine, 101 (1) (2007), pp. 162-168. Reference #2: M. Mokhtari, P.B. Bach, P.A. Tietjen, D.E. Stover. Bronchiolitis obliterans organizing pneumonia in cancer: a case series. Respiratory Medicine, 96 (4) (2002), pp. 280-286. DISCLOSURES: no disclosure on file for Guillermo Garrido;No relevant relationships by Anita Gopalakrishnan No relevant relationships by Rameez Rao No relevant relationships by Mohammad Salimian
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SESSION TITLE: Problems in the Pleura Case Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), approved for treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia (CLL). There is an association of increased risk of bleeding with ibrutinib due to platelet dysfunction caused by the medication. Bleeding is usually non-life threating such as subcutaneous or mucosal bleeding, epistaxis, and ecchymosis. But major bleeding has been reported such as intracranial hemorrhage and gastrointestinal hemorrhage. Thoracic complications from ibrutinib are rare. Below is a case report discussing a hemorrhagic pleural effusion thought to be caused by Ibrutinib. CASE PRESENTATION: Patient is a 78-year-old male initially diagnosed with CLL on flow cytometry showing a low-grade B cell lymphoproliferative process. Patient was monitored by Hematology and when kappa light chain numbers began to rise, a bone marrow biopsy was performed showing 90% infiltration of the marrow with lymphoid cells. Patient was started on Ibrutinib therapy and responded well to treatment. A year after starting therapy, patient presented to the emergency room with increased shortness of breath and fatigue. Patient was found to be COVID-19 positive and chest x-ray showed a large right sided pleural effusion. Thoracentesis was performed draining 1650cc of bloody fluid. Fluid studies revealed a lymphocytic effusion with RBC count 1,185375, WBC of 1751. Cultures and cytology were negative. On further history, patient was without recent trauma or surgery, CTA chest was negative for pulmonary embolism. QuantiFERON Gold test was negative, indicating low likelihood of tuberculosis. Patient was not on any antiplatelet or systemic anticoagulation medications. Ibrutinib therapy was held during hospitalization and pleural effusion did not reaccumulate. Patient passed away during hospital stay secondary to respiratory failure due to COVID-19. DISCUSSION: Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib predisposes to bleeding by inhibiting BTK and Tec, which play a role in the inhibitory signaling pathway of platelet collagen receptors such as glycoprotein VI (GP VI) and C-type lectin-like receptor 2 (CLEC-2). Our patient had no other risk factors for developing a hemorrhagic effusion. CLL itself can cause malignant effusions, one study found the incidence of malignant effusions among patients with CLL to be 9%, but the effusion was noted to be serous or serosanguinous and there was pleural involvement in all patients which was not the case in our patient. CONCLUSIONS: There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. It is important to realize bleeding complications related to ibrutinib therapy can occur. Reference #1: Shatzel JJ, Olson SR, Tao DL, McCarty OJT, Danilov AV, DeLoughery TG. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost. 2017;15(5):835-847. doi:10.1111/jth.13651 Reference #2: Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-2437. doi:10.1056/NEJMoa1509388 Reference #3: Paydas S. Management of adverse effects/toxicity of ibrutinib. Crit Rev Oncol Hematol. 2019;136:56-63. doi:10.1016/j.critrevonc.2019.02.001 DISCLOSURES: No relevant relationships by fatima ali No relevant relationships by Joan Wiley