Diagnosis Of Chronic Lymphocytic Leukemia Research Articles

Herpes zoster in chronic lymphocytic leukemia: Effect of vaccination and treatment.

7527 Background: Patients with Chronic Lymphocytic Leukemia (CLL) are susceptible to infections due to impaired humoral immunity as a complication of the disease, treatments received and age at diagnosis. Herpes zoster (HZ) is a painful, vesicular rash from reactivation of varicella-zoster virus that is common in immunocompromised patients. While HZ vaccines can reduce both varicella-zoster reactivation and post-herpetic neuralgia, vaccination rates are low. The aim of this study is to determine the effect of vaccination on rates of HZ infection in patients with CLL. Methods: We identified patients diagnosed with CLL between September 1999 and October 2015 using Veterans Administration Central Cancer Registry (VACCR). Pharmacy records were used to identify patients who received treatment for CLL and HZ. HZ events were defined as patients with International Classification of Diseases 9th Revision (ICD-9) codes for HZ infection (053) or prescriptions of acyclovir or valacyclovir at a dose of 1500 mg/day or higher or famciclovir at a dose of 1000 mg/day or higher without a diagnosis of Herpes simplex or Bell’s palsy, or an ICD-9 code and prescription above. Cox proportional hazards regression model was used to assess the association between vaccination as a time-varying exposure and developing HZ while controlling age at CLL diagnosis, co-morbidity score, and receipt of first and second line chemotherapy. The study was approved by the St. Louis VA Medical Center institutional review board. Results: A cohort of 7155 patients with CLL was identified using VACCR. 2640 patients (36.9%) and 1161 patients (16.2%) received first and second line chemotherapy respectively. Mean age at first chemotherapy was 69.5 years. We detected 1115 cases of HZ (15.6%) using ICD-9 codes, prescriptions or both. 615 patients (8.6%) received HZ vaccinations. Patients with HZ were younger (mean 68.0 vs. 69.8 years, p < 0.001), had similar co-morbidities, and were more likely to get treatment for CLL (58.1% vs. 33.0%, p < 0.001). Using a time-varying analysis, there was a trend for HZ vaccine to decrease the risk of developing HZ (HR 0.71, 95% CI 0.49-1.04, p = 0.082). When adjusting for age and co-morbidity, patients with CLL treated with first line chemotherapy had a higher risk of HZ (HR 2.34, 95% CI 2.02-2.71, p < 0.001) compared to those never receiving therapy. Second line chemotherapy increased risk of HZ (HR 1.32, 95% CI 1.13-1.55, p < 0.001) beyond first line treatment. Conclusions: HZ is prevalent in patients with CLL and affects younger patients who require chemotherapy. The risk of developing HZ increases in recipients of first and second line chemotherapy. In the time-varying analysis, there was a trend towards decreased infection in patients who received HZ vaccination. Further studies in a more modern cohort that assess infection risk using a larger vaccinated group with the newer and more effective HZ vaccine are warranted.

Survival trends in chronic lymphocytic leukemia in the era of oral targeted therapies in the United States: SEER database analyses (1985 to 2017).

7524 Background: The survival of chronic lymphocytic leukemia (CLL) patients has progressively improved after the approval of new targeted therapy for first-line treatment and relapsed disease. We performed a corresponding analysis from the U.S. population-based SEER database (1973–2017) to explore the trend of survival and the effect of advanced CLL treatment on overall survival in CLL patients. Methods: Data were extracted from SEER*Stat for all patients 15 years or older with a primary diagnosis of CLL with or without subsequent cancers. A period analysis was performed to estimate the 5- and 10-year relative survival rates for patients diagnosed (dx) during different calendar periods from 1985 to 2017, based on gender and age at time of diagnosis (15–44, 45–54, 55–64, 65–74, 75–84, 85 years or older). A mixture cure model was used to examine the proportion of long-term survivors per gender and age category among CLL patients diagnosed between 1985 and 2015. Cox proportional hazard modeling was used to calculate the hazard ratios (HRs) of death adjusted for gender and age at diagnosis for two cohorts: (a) diagnosed in 2000–2003 and followed to 2012; (b) 2004–2007 and followed to 2015. Results: For males, the 5-year age-adjusted relative survival rate improved progressively from 72.0% (dx 1985-1989) to 88.2% (dx 2010-2014); for females, from 76.8% (dx 1985-1989) to 90.8% (dx 2010-2014). The corresponding 10-year age-adjusted relative survival rates were 47.3% (dx 1985-1989) and 72.5% (dx 2005-2009) for males; and 58.2% (dx 1985-1989) and 78.7% (dx 2005-2009) for females. The table below shows the proportions of long-term survivors for the 1985–2017 cohort as estimated in the mixed cure model. The HRs (95%CI) of death for cohort (b) in comparison to cohort (a) were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.67), 0.68 (0.54–0.85); and 0.83 (0.68–1.02) for age categories of 45–54, 55–64, 65–74, 75–84, and 85 years or old. Conclusions: Survival is significantly improved by calendar period among patients diagnosed after 2004 and treated in the era of advanced therapies. Females and younger patients had a higher probability of long term survival. Future studies should consider such covariates as treatment type, disease stage and genetics.[Table: see text]

A 10-color flow cytometry panel for diagnosis and minimal residual disease in chronic lymphocytic leukemia

Diagnosis and minimal residual disease (MRD) monitoring of chronic lymphocytic leukemia (CLL) by flow cytometry currently requires multiple antibody panels. We added CD23 and CD200 to the EuroFlowTM lymphoid screening tube (LST) to create a 10-color modified LST (mLST) capable of diagnosing typical CLL in a single tube. We then explored if the mLST could be used for MRD by comparing its performance to the European Research Initiative on CLL (ERIC) panel using spiked cryopreserved and fresh patient samples. Over 1 year of use in our clinical laboratory, the mLST diagnosed CLL without further immunophenotyping in 56% of samples with an abnormal clone. There was good agreement in MRD results between the mLST and ERIC panels. Therefore, the mLST can streamline CLL diagnosis by reducing technician time and the number of panels required. It may have the potential to screen for MRD in laboratories without access to dedicated panels (ERIC).

The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment.

The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients.

CHRONIC LYMPHOBLASTIC LEUKEMIA DIAGNOSED BY PRIMARY CUTANEOUS LESION

Chronic lymphocytic leukemia (CLL) is a malignant, low-grade, monoclonal disorder characterized by the accumulation of lymphocytes with variable clinical features. Cutaneous manifestations or leukemia cutis are non-specific, uncommon presentations of CLL and can present in many different ways. In this case report, we discuss a 76-year-old male who presented with skin lesions of the lower limbs and severe itching. Due to the lack of response to the treatment with topical corticosteroids, initial tests were carried out. Complete blood count results indicated lymphocytosis. Eventually Ultimately, the skin lesions led to the diagnosis of CLL. The patient was treated with bendamustine-rituximab (BR). After receiving the treatment, all cutaneous manifestations and generalized itching disappeared. This case highlights the importance of comparing similar cases of CLL presented with dermatological conditions in order to to understand proper management and practice.

CORRELATION OF TRISOMY 12 WITH CLINICAL FEATURES AND OTHER LABORTARY PARAMETERS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKAEMIA

Objective: To determine the frequency of trisomy 12 in B-Cell chronic lymphocytic leukaemia (CLL), to correlate its association with clinico-pathologic features and to determine the role of this cytogenetic defect to the prognosis.
 Study Design: Cross sectional study.
 Place and Duration of Study: Haematology department, Armed Forces Institute of Pathology, Rawalpindi, from May 2017 to Aug 2018.
 Methodology: A total of 56 newly diagnosed patients of Chronic Lymphocytic Leukaemia were included in the study. Patients were diagnosed on the basis of National Cancer Institute Working Group guidelines. A detailed history and thorough clinical examination were performed and complete blood counts, biochemical profile, bone marrow examination, immunophenotyping on bone marrow/peripheral blood samples were done for the diagnosis of Chronic lymphocytic leukaemia. Interphase FISH studies were performed on blood/bone marrow aspiration for detection of Trisomy 12 were performed.
 Results: Out of 56 patients, trisomy was detected in 12 (10.7%) patients. Out of 7 patients with trisomy 12, five patients presented in late stages (Binet stage B and C), however this association of Trisomy 12 with Binet stage was also statistically insignificant (p=0.474). About six with trisomy 12 were positive for CD 38, however this association was also not statistically significant (p=0.124). Results revealed that patients having trisomy 12 underwent chemotherapy at diagnosis and during follow ups as compared to patients having other cytogenic abnormalities. Moreover, patient with trisomy 12 develop progression in disease during course of illness, however association was statistically insignificant (p>0.05)............

Combined chronic myeloid leukaemia and chronic lymphocytic leukaemia in five patients, including one with 17p deletion.

We report a series of five Australian cases of chronic lymphocytic leukaemia (CLL) occurring concurrently with chronic myeloid leukaemia (CML). Patient management including therapies and response together with clinical progress was obtained from medical records and laboratory information systems. Prior to CML diagnosis, all five had a preceding diagnosis of CLL. Three had received prior fludarabine. All received tyrosine kinase inhibitors (TKI). None required subsequent therapy for CLL. One patient had 17p deletion CLL and another patient had normal CLL cytogenetics. All currently have satisfactory blood counts with quantitative polymerase chain reaction for CML showing molecular response. All remain alive. Thus, such cases can be successfully managed by treating each haematological disorder in the usual manner. The control achieved in CML with the TKI enables satisfactory marrow function to recover in patients with concomitant CLL. The role for allograft in patients with dual malignancies is uncertain and needs to be individualised depending on control of each malignancy.

A Tissue Counterpart to Monoclonal B-Cell Lymphocytosis.

B-cell clones discovered in tissue biopsies, without overt lymphoma, may represent a tissue counterpart to peripheral blood monoclonal B-cell lymphocytosis (MBL), herein termed tMBL. To characterize the clinicopathologic features of tMBL. During a 10-year period, we retrospectively identified non-bone marrow/peripheral blood cases with monotypic B cells detected by tissue-based flow cytometry but without an identifiable lymphomatous infiltrate on routine histopathology. We excluded cases with prior diagnosis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma or MBL. Fifty-four cases were identified (35 lymph node, 3 splenic, and 16 soft tissue/viscera). Forty-six cases were CLL-type, 2 were atypical CLL, and 6 were non-CLL. tMBL was detectable by immunohistochemistry in 14 cases (26%, all CLL-type). Concurrent blood flow cytometry, available in 10 cases, showed 4 with low-count MBL (3 CLL-type, 1 with non-CLL-type), 5 with high-count MBL (all CLL-type), and 1 case negative for clonal population. With median follow-up of 51 months, 2 patients had progression of disease (CLL, 68.7 months; and diffuse large B-cell lymphoma, 5.9 months). Patients with immunohistochemistry-detectable tMBL had increased monoclonal B cells per total lymphocyte events (P = .01), morphologic evidence of bone marrow involvement (P = .04), higher white blood cell count (P = .02), and increased absolute lymphocyte count (P = .02). tMBL spans an immunophenotypic spectrum similar to MBL, is detectable by immunohistochemistry in a minority of cases (often CLL immunophenotype), and is likely systemic in most cases. Development of overt lymphoma is uncommon but may occur, warranting clinical follow-up.

Recommendations for chronic lymphocytic leukaemia dia gnosis and therapy 2021

Recommendations for chronic lymphocytic leukaemia dia gnosis and therapy 2021

The contribution of CD200 to the diagnostic accuracy of Matutes score in the diagnosis of chronic lymphocytic leukemia in limited resources laboratories.

Flow cytometry immunophenotyping has an essential role in distinguishing chronic lymphocytic leukemia from other B-chronic lymphoproliferative disorders. Recently, CD200 is considered as a relatively consistent marker in chronic lymphocytic leukemia. We retrospectively assessed CD200 expression in 252 patients with B chronic lymphoproliferative disorders with four-color flow cytometry. CD200 expression estimation included the proportion of positive cells (≥30%) and the mean fluorescence intensity ratio. Additionally, we have incorporated CD200 into Matutes score, also replaced FMC7 and CD79b in an attempt to improve the score discriminative power. Of 252 patients enrolled, 199(79%) patients were classified as chronic lymphocytic leukemia and 53 (21%) as other B-chronic lymphoproliferative disorders. All chronic lymphocytic leukemia cases and 20 of 53 (37.7%) of other B-chronic lymphoproliferative disorders demonstrated high CD200 expression (≥30%). Further, CD200 (≥30%) revealed a higher accuracy in comparison to other markers in Matutes score (range: 51%–92.5%). Also, CD200 addition to the Matutes score has correctly recognized all 199 chronic lymphocytic leukemia cases including 10 atypical chronic lymphocytic leukemia cases. As for non-CLL cases, 20 of 53 attained a higher score, yet keeping the original diagnosis. Moreover, CD200 enhanced the diagnostic accuracy of Matutes score to 100%, and when included in a simplified 4-markers score, showed an accuracy of 99.8% compared to 99.4% of Matutes score. In conclusion, CD200 is an accurate diagnostic marker for chronic lymphocytic leukemia, and can refine the modified Matutes score accuracy when added with other markers.

Hronična limfocitna leukemija u ordinaciji opšte medicine

Introduction: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, rarely affecting children. It is more common in males over 60. Etiopathogenetically, it represents an abnormal proliferation of lymphocytes in the bone marrow, which are dysfunctional although morphologically similar to mature ones. Case report: Female patient, 66, a housewife, comes for an examination due to fatigue lasting about a month and weight loss of 3-4 kg. She denies other health problems. On the examination, she is alert, oriented to time, space, and persons, eupnoeic, lymphadenopathy on the neck, axillae and groins. She gives away the impression of a patient with mild clinical symptoms. Clinical examination: clear breath sounds in all lung fields, regular heartbeat, clear tones, BP 140/80 mmHg, abdomen at chest level, painless to palpation, liver not palpable, and spleen palpated 2 cm below the costal arch. CBC (complete blood count) showed an increased number of leukocytes 181.30x109 /L and lymphocytosis 92.2%, other parameters were normal. She was referred to the hematologist in the Kraljevo General Hospital, where further diagnostics were performed. Blood count was repeated, Chest X-ray was performed, ultrasound (US) of the abdomen neck, axillae, groins, and heart, virology tests, ENT examination. Abdominal US showed a pathological finding with enlarged liver, spleen, lymph nodes (LN). ENT examination: enlarged tonsils, other findings unremarkable. Since chronic lymphocytic leukemia was suspected, she was referred to the Clinical Center of Serbia. Immunophenotyping (IF) and computed tomography (CT) of the neck, chest, and abdomen were performed. The diagnosis of CLL was confirmed. A Medical Council decided to perform immunochemotherapy (IHT) with fludarabine and rituximab. After 6 received cycles, the patient feels well and the CBC parameters are normal. Conclusion: CLL may be asymptomatic or nonspecific and with mild symptoms in a large number of patients. Therefore, blood tests with leukocytosis and absolute lymphocytosis findings are crucial to suspect the disease and perform further diagnostics.

Chronic Lymphocytic Leukaemia Unmasked by COVID-19 Infection: A Case Report

Corona Virus Disease 2019 (COVID-19) caused by SARS Cov-2 is an Ribonucleic Acid (RNA) virus which spreads through respiratory route. It was first detected in Wuhan, China in December 2019. World Health Organisation (WHO) declared it as worldwide pandemic in March 2020. Clinically, it can present from mild flu like disease to severe respiratory illness. Reverse Transcription Polymerase Chain Reaction (RT-PCR) is the method for confirmation. Chronic lymphocytic leukaemia is a lymphoproliferative disorder that presents as absolute lymphocytosis with proliferation of monoclonal mature B lymphocytes, unlike other causes of reactive lymphocytosis. Patients with chronic lymphocytic leukaemia often have defects in humoral and cellular immune system. Therefore, these patients have strong predisposition to recurrent infections and in this case for COVID-19. The relationship between chronic lymphocytic leukaemic and COVID-19 is not very clearly understood. A 77-year-old male with no significant co-morbidities presented with cough, fever and shortness of breath. His High-Resolution Computed Tomography (HRCT) chest revealed non-specific interstitial pneumonia and was tested positive for COVID-19 infection on RT-PCR. A Complete Blood Count (CBC) showed a high Total Leukocyte Count (TLC) with absolute lymphocytosis. There was absence of lymphadenopathy or splenomegaly. Flow cytometry confirmed the diagnosis of Chronic lymphocytic leukaemia. He was offered convalescent plasma therapy and later had to be incubated because of multiorgan failure. His Absolute Lymphocyte Counts (ALC) more than doubled in a week’s time. COVID-19 infection usually presents with lymphopenia, lymphocytosis should always raise a suspicion of underlying haematological malignancy or secondary infection.

Comorbidities at Diagnosis, Survival, and Cause of Death in Patients with Chronic Lymphocytic Leukemia: A Population-Based Study.

This study aimed to examine the prevalence of comorbidities in patients diagnosed with chronic lymphocytic leukemia (CLL), and to assess its influence on survival and cause-specific mortality at a population-based level. Incident CLL cases diagnosed in the Girona province (Spain) during 2008–2016 were extracted from the Girona Cancer Registry. Rai stage and presence of comorbidities at diagnosis, further categorized using the Charlson comorbidity index (CCI), were obtained from clinical records. Observed (OS) and relative survival (RS) were estimated and Cox’s proportional hazard models were used to explore the impact of comorbidity on mortality. Among the 400 cases included in the study, 380 (99.5%) presented at least one comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most common disease. 5-year OS and RS were 68.8 (95% CI: 64.4–73.6) and 99.5 (95% CI 3.13–106.0), respectively, which decreased markedly with increasing CCI, particularly in patients with CCI ≥ 3. Multivariate analysis identified no statistically significant association between the CCI and overall CLL-related or CLL-unrelated mortality. In conclusion, a high CCI score negatively influenced the OS and RS of CLL patients, yet its effect on mortality was statistically non-significant when also considering age and the Rai stage.

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.

Chronic Lymphocytic Leukaemia Presenting with Pancytopenia: ARare Haematological Coincidence

Chronic Lymphocytic Leukaemia (CLL) is commonly associated with autoimmune cytopenias but CLL presenting with pancytopenia is a rare occurrence. Here, we present a case of 56-year-old male patient, who presented with pallor, mild hepatosplenomegaly, right-sided pleural effusion in chest x-ray, pancytopenia and his bone marrow showed infiltration by mature appearing lymphoid cells making a diagnosis of CLL. Despite the frequency of these immune mediated cytopenia, only few cases of pancytopenia have been described so far to the best of our knowledge. Hence, to emphasise the rarity of such haematological coincidence we are presenting this case report. CLL generally presents with persistent absolute lymphocytosis on peripheral smear with an absolute monoclonal lymphocyte count of more than 5000/cumm. There is a common association with Autoimmune Haemolytic Anaemia (AIHA) and Immune Thrombocytopenia (ITP) and the association is called as Evan’s syndrome. Its pathogenesis is associated with autoimmune process. AIHA, ITP, and Pure Red Cell Aplasia (PRCA) are commonly associated complications seen in CLL. The pathogenesis of AIHA and ITP are antibody this inplace of the reactions and abnormal T cell activity is noted in the pathogenesis of PRCA. Despite of the frequency of these immune mediated cytopenias noted in CLL, bone marrow was seen to be hypercellular in most of the cases and marrow hypoplasia have been reported in only 2 cases reported in literature so far. In the present case, although pancytopenia was present on peripheral blood smear examination but bone marrow was hypercellular for age with diffuse infiltration by monoclonal mature appearing lymphoid cells which makes this case all the more interesting. Despite repeated blood transfusions,antiviral drug Tenofovir and aggressive supportive measures for 6 months, he developed right-sided pleural effusion and succumbed to his illness.

Checkpoint Blockade in Melanoma Patients With Underlying Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is associated with immune dysfunction and an increased risk of melanoma. For patients with metastatic melanoma, immunotherapy with checkpoint blocking antibodies is a standard of care. In patients with concomitant CLL and metastatic melanoma, it is not known whether CLL might influence the antimelanoma efficacy or immune-related toxicities of immune checkpoint blockade. Fifteen patients with locally advanced or metastatic melanoma and a concomitant diagnosis of CLL who received pembrolizumab or ipilimumab with or without nivolumab for the treatment of their melanoma at Memorial Sloan Kettering Cancer Center between January 1, 2010, and January 1, 2017, were retrospectively identified. Clinical characteristics including absolute lymphocyte counts during therapy were recorded along with a response to treatment (objective radiographic response, progression-free survival, and adverse events) for each patient. Of 9 response-evaluable patients treated with ipilimumab, 3 (33%) had a partial response, 1 (11%) had stable disease, and 5 (56%) developed progressive disease. Objective tumor responses were also observed with single-agent therapy pembrolizumab and with combination therapy of nivolumab and ipilimumab. Grade 3 or 4 toxicity was observed in 6 of 15 patients (40%), including diarrhea, transaminitis, rash, and hemolytic anemia. Although our retrospective assessment was limited, there was no evidence that CLL responded to the checkpoint blockade. This case series demonstrates that ipilimumab, pembrolizumab, and combined ipilimumab and nivolumab therapies show clinical activity in patients with melanoma and concomitant CLL, at rates consistent with those previously reported. This population may warrant closer surveillance for hematologic immune-related toxicities such as autoimmune hemolytic anemia.

PBI8 Use of Biosimilars in Haematology in France: A Descriptive Study Based on a French Medico-Administrative Database

Two biosimilars (Truxima® and Rixathon®) from the reference product Mabthera® (rituximab) indicated in non-Hodgkin’s lymphoma (nHL) and chronic lymphocytic leukaemia (CLL) were introduced in France by the end of 2017. The objective of this study was to describe the financial impact of the introduction of these two biosimilars in France. The EGB (Echantillon Généraliste de Bénéficiaires) database, a 1/97th random sample of the French healthcare insurance database linked with the hospital discharge database (PMSI) was used. Patients were identified for the years 2017 and 2018 through admissions with haematologic diagnosis (follicular lymphoma, non-follicular lymphoma, non-Hodgkin’s lymphoma, malignant immunoproliferative diseases and chronic lymphocytic leukaemia). The impact was assessed by comparing market shares of the reference product from 2017 to 2018 in terms of number of unique patients and total number of admissions. The financial impact was extrapolated to the national level from the national health insurance perspective. The study identified 195 and 215 patients for 2017 and 2018 respectively, with either a diagnosis of nHL or CLL and receiving at least one dose of rituximab. In 2017, Mabthera® was administered mostly to patients with other non-follicular lymphoma (40%) and follicular lymphoma (26%). The cost of Mabthera® was estimated at €472 million in 2017. By 2018, unique patients who were administered Mabthera® decreased by 35%, and financial cost by 65% (€303 million). In 2018, biosimilars were administered for 53% in other non-follicular lymphoma, 33% in follicular lymphoma, 66% in CLL, 52% in other non-Hodgkin's lymphoma, and 77% in Malignant immunoproliferative diseases, for cost of €202 million. Biosimilars were administered only in regional public hospitals and mostly in outpatient admissions. These results show that introduction of biosimilars of rituximab induced €100 million savings from the national health insurance perspective.

Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

Clinico-Biological, Molecular and Prognostic Features of Patients with Diffuse Large B-Cell Lymphoma-Variant of Richter Syndrome: A Multicenter Retrospective Study of the French Innovative Leukemia Organization

Risk Factors for the Development of Skin Cancers in Patients with Chronic Lymphocytic Leukemia: A Retrospective Cohort Study

Introduction: Individuals with chronic lymphocytic leukemia (CLL) are often immunosuppressed and at increased risk of infection and secondary malignancies. The primary aim of this study was to determine the incidence of skin cancer amongst the CLL population at Kingston Health Sciences Centre (KHSC), Ontario, Canada. Secondly, we sought to identify the risk factors associated with the development of skin cancer in CLL patients. Methods: Consecutive patients seen at KHSC with a diagnosis of CLL between 2014 January 1 and 2019 December 31 formed the primary study cohort. KHSC serves a region of ~ 550,000 including a high proportion of older individuals and those living in rural areas. Approval was provided by Queen's University Research Ethics Board. Four independent reviewers conducted retrospective electronic chart review, initially in duplicate with review of any areas of discrepancy to ensure a standardized approach. Data collected included age, sex, CLL date of diagnosis, stage, genetics and treatment; histological diagnoses of other cancers (skin and other), smoking status (ever/never) and date of last follow up or death. The primary outcome was the development of the first skin cancer (squamous cell carcinoma, basal cell carcinoma, melanoma, or sarcoma) confirmed via pathology reports that are available in our local institution. All statistical analysis was performed using SAS Enterprise v. 7.15. Categorical variables were compared using chi-square or Fisher exact tests, medians using Wilcoxon and Mann-Whitney tests, and continuous variables using t-tests. Risk factors for development of skin cancer were assessed using multivarable Cox-proportional hazard models. Results: Of the total cohort of 377 individuals with CLL, 251 (67%) were male. Median age at diagnosis of CLL was 65 years (range 36 - 93 years of age). Median follow-up from the time of CLL diagnosis was 6.5 years (range 0.27 - 30.98). Of these, 80 individuals (21.2%) developed at least one skin cancer after their diagnosis of CLL, with an age-adjusted incidence of 16.96/1000 patient years (95% CI 12.5 - 23). Among the 297 who did not develop skin cancer post-CLL diagnosis, 13 individuals who had documented skin cancer pre-CLL diagnosis only, are included in the non-skin cancer group (Figure 1). Females had a lower incidence of skin cancer compared with males (63 males versus 17 females, p=0.009). There was no difference between the groups based on Rai stage at diagnosis, smoking history, or IGHV /p53 status. Individuals treated with ibrutinib had a lower incidence of skin cancer (3 versus 49, p=0.002). Development of skin cancer was associated with development of other invasive tumours including CLL transformation (p=0.001) (Table 1). Conclusion: Limitations of this study include its small size, and single institution setting. Our data likely reflect a conservative estimate as skin cancers may be diagnosed outside of the institution, and not all CLL is treated at tertiary care centres. Consistent with other studies we found that males with CLL are at increased risk of developing skin cancer, as compared to females. Individuals with CLL and skin cancer were more likely to develop another malignancy or Richter's transformation. The finding of lower incidence of skin cancer with ibrutinib treatment is novel; further investigation in larger populations is needed to determine if it may offer a protective effect. Disclosures Asai: Sanofi Canada: Honoraria, Research Funding; AllerGen NCE: Research Funding; Pfizer: Honoraria, Research Funding; Janssen: Honoraria; Leo Pharma: Honoraria; Eli Lilly: Honoraria; Novartis: Honoraria; Abbvie: Honoraria, Research Funding; Canadian Institutes of Health Research: Research Funding. Hay:Roche: Research Funding; Janssen: Research Funding.

Complex Karyotype Subtypes at Chronic Lymphocytic Leukemia Diagnosis Refine the Risk of Developing a Richter Syndrome. the Richter Syndrome Scoring System

Complex Karyotype Subtypes at Chronic Lymphocytic Leukemia Diagnosis Refine the Risk of Developing a Richter Syndrome. the Richter Syndrome Scoring System