Diagnosis Of Chronic Lymphocytic Leukemia Research Articles

Laboratory analysis of 124 chronic lymphocytic leukemia cases: Single center study

Abstract BACKGROUND: Chronic lymphocytic leukemia (CLL) is a disease characterized by an uncontrolled proliferation of malfunctioning mature B-lymphocytes. It represents a variable range of clinical presentation and prognoses. Understanding the demographic and cellular characteristics of CLL patients can aid in better disease management and treatment outcomes. OBJECTIVES: To identifying hematological parameters and patterns and potential markers that could assist in better diagnosis and of CLL in the local population. PATIENTS, MATERIALS AND METHODS: A retrospective analysis of 124 cases of newly diagnosed CLL was conducted. Data were collected from reports over 2 years (April 2022-April2024), including demographics, Hb levels, WBC counts, platelet counts and expression of CD markers (5, 19, 20, 23, 200, FMC7, LAIR1 and others) using flow cytometry on peripheral blood specimens. Based on FC findings, patients were categorized into two groups for better assessment; definite diagnosis CLL and possible diagnosis CLL; then further subdivided into poor prognosis CLL and good prognosis CLL. RESULTS: Male patients represented 59.5% of cases and females were 40.5% with a median age of 61 years at diagnosis. The mean Hb level was 109 ± 2 g/L, the mean WBC count was 58.0 ± 25.0 × 109/L, and the mean platelet count was 190 ± 40 × 109/L. CD5 was positive in 97.6% of cases, with CD23 in 96%. CONCLUSION: This study provides an overview of the demographic and cellular marker characteristics of CLL patients in FC unit. The findings underscore the heterogeneity of CLL immunophenotype and the importance of detailed characterization in improving patient management protocols; however, further research is warranted to correlate these findings with other parameters of disease burden and prognosis to optimize the therapeutic approaches for CLL patients.

A 47-Year-old Asian female with tracheobronchial space-occupying lesions caused by chronic lymphocytic leukemia

Case presentationA 47-year-old Asian woman was admitted with worsening chest tightness and dyspnea for 10 days. Computed tomography (CT) showed changes in the trachea and segmental bronchi. Pulmonary function results suggestive of severe obstructive ventilatory dysfunction. Bronchoscopic findings showed the presence of multiple nodular lesions in the patient’s trachea and left and right main bronchi. Bronchoscopic biopsy, lymph node biopsy and bone marrow aspiration flow cytometry test results led to a definitive diagnosis of chronic lymphocytic leukemia (CLL), staged as Binet stage B and Rai stage 2.

Mantle cell lymphoma with skin involvement: Case report of a rare manifestation in a patient with initial diagnosis of chronic lymphocytic leukemia

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin's lymphoma, which mainly affects males. It has a variable clinical presentation, with a course ranging from indolent cases that do not require treatment for years to very aggressive cases. Skin involvement is a rare event. Although most patients have disease in stage III or IV at diagnosis, they generally present with good functional status. In immunohistochemistry, CD5 is commonly expressed, a feature it shares with chronic lymphocytic leukemia. Cyclin D1 and SOX11 expression are present in almost all cases. Treatment depends on multiple factors such as age, frailty, comorbidities, disease stage, symptoms and morphological characteristics. We present the case of a male patient initially diagnosed with chronic lymphocytic leukemia who was started on treatment with ibrutinib. A biopsy of the right earlobe was subsequently performed, which documented secondary skin involvement due to a classic histological variant of mantle cell lymphoma. The patient was treated with chemotherapy between March and July 2022, with positron emission tomography at the end of the proposed cycles with complete metabolic response, so maintenance treatment with rituximab was performed and subsequently consolidated with an autologous bone marrow transplant. To date, the patient is in remission of the disease.

Atezolizumab, venetoclax, and obinutuzumab combination in Richter transformation diffuse large B-cell lymphoma (MOLTO): a multicentre, single-arm, phase 2 trial

The diffuse large B-cell lymphoma (DLBCL) variant of Richter transformation (DLBCL-RT) is typically chemoresistant with poor prognosis. Aiming to explore a chemotherapy-free treatment combination that triggers anti-tumour immune responses, we conducted a phase 2 study of atezolizumab (a PD-L1 inhibitor) in combination with venetoclax and obinutuzumab in patients with DLBCL-RT. This was a prospective, open-label, multicentre, single-arm, investigator-initiated, phase 2 study in 15 hospitals in Italy and Switzerland. Eligible patients had a confirmed diagnosis of chronic lymphocytic leukaemia or small lymphocytic lymphoma as per the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with biopsy-proven transformation to DLBCL; had not previously received treatment for DLBCL-RT, although they could have received chronic lymphocytic leukaemia therapies; were aged 18 years or older; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. No previous treatment with any of the drugs in the triplet combination was allowed. Patients received 35 cycles of 21 days of intravenous obinutuzumab (100 mg on day 1, 900 mg on day 2, 1000 mg on day 8 and day 15 of cycle 1; 1000 mg on day 1 of cycles 2-8) and intravenous atezolizumab (1200 mg on day 2 of cycle 1 and 1200 mg on day 1 of cycles 2-18), and continuous oral venetoclax (ramp-up from 20 mg/day on day 15 of cycle 1 according to chronic lymphocytic leukaemia schedule, then 400 mg/day from day 1 of cycle 3 to day 21 of cycle 35). The primary endpoint was overall response rate at day 21 of cycle 6 in the intention-to-treat population. We considered an overall response rate of 67% or more to be clinically active, rejecting the null hypothesis of a response of 40% or less. The study is registered with ClinicalTrials.gov, NCT04082897, and has been completed. Between Oct 9, 2019, and Oct 19, 2022, 28 patients were enrolled (12 [43%] male patients and 16 [57%] female patients). Median follow-up was 16·8 months (IQR 7·8-32·0). At cycle 6, 19 of 28 patients showed a response, yielding an overall response rate of 67·9% (95% CI 47·6-84·1). Treatment-emergent adverse events that were grade 3 or worse were reported in 17 (61%; 95% CI 40·6-78·5) of 28 patients, with neutropenia being the most frequent (11 [39%; 21·5-59·4] of 28 patients). Serious treatment-emergent adverse events were reported in eight (29%; 14·2-48·7) patients, which were most commonly infections (five [18%; 6·1-36·9] of 28 patients). There were two (7%) deaths attributable to adverse events during the study: one from sepsis and one from fungal pneumonia, which were not considered as directly treatment-related by the investigators. Six (21·4%) patients had immune-related adverse events, none of which led to discontinuation. No tumour lysis syndrome was observed. The atezolizumab, venetoclax, and obinutuzumab triplet combination was shown to be active and safe, suggesting that this chemotherapy-free regimen could become a new first-line treatment approach in patients with DLBCL-RT. Roche.

Infections and their prognostic significance before diagnosis of chronic lymphocytic leukemia, non-Hodgkin lymphoma, or multiple myeloma

BackgroundImmunodeficiency is a shared feature of B cell malignancies. The risk of infections and their prognostic significance after diagnosis are well characterized, but, conversely, less is known about prediagnostic infections in these domains.MethodsIn matched case-control analyzes, using Danish nationwide registers, we assessed the rate of prediagnostic infections in chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), multiple myeloma (MM), follicular lymphoma (FL), marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL). Survival analyzes of data from clinical registers were then used to determine the effect of infections in the year preceding diagnosis on overall survival. To yield results for as many patients as possible, antimicrobial prescriptions were used as surrogates for infections.ResultsThe nationwide and clinical registers comprised 30,389 patients, accumulating 213,649 antimicrobial prescriptions, and 18,560 patients accumulating 107,268 prescriptions, respectively. The relative risk of infections was increased up to 15 years prior to diagnosis of malignancy and markedly increased in the year just prior to diagnosis. More than two antimicrobials within one year prior to diagnosis were associated with significantly shorter overall survival, independently of known prognostic factors.ConclusionPatients with B cell-derived malignancies exhibit marked immunodeficiency several years prior to diagnosis such that different disease subtypes demonstrate both overlapping and distinct trends in infection risk preceding diagnosis. Moreover, multiple infections within the year preceding diagnosis are independently associated with shorter overall survival for all the examined malignancies.

Chronic Lymphocytic Leukemia in Pregnancy: A Review of the Available Literature and the Pharmacological Challenges in Management.

Chronic lymphocytic leukemia (CLL) is a rare hematologic malignancy to occur in pregnancy, with an estimated incidence of 1 in 75,000 pregnancies. Pregnant women with CLL face increased susceptibility to infections, due to a weakened immune system. Higher risks of fetal malformations and death are associated with CLL treatment during pregnancy, emphasizing the need for careful consideration and management in these cases. This review aimed to summarize the current evidence regarding the diagnosis, prognosis, and treatment of CLL in pregnant cases. A comprehensive search strategy was employed across multiple databases, yielding 14 case reports for inclusion. The cases were divided based on CLL diagnosis onset, either before or during pregnancy. Our results showed that patients diagnosed during pregnancy (n = 5) were mostly asymptomatic at diagnosis, with management ranging from supportive care to leukapheresis and transfusions. Postpartum treatment varied, with some patients requiring no additional therapy and others receiving chemotherapy. Pregnancy outcomes were generally favorable, with most neonates born healthy at term. However, one case of Richter transformation resulted in maternal death despite treatment. Among patients with pre-existing CLL (n = 9), the majority experienced an indolent course during pregnancy, with only supportive care required. A few cases necessitated treatment due to progressive disease or complications, including chemotherapy, leukapheresis, and splenectomy. This review highlights the heterogeneous nature of CLL in pregnancy and the importance of individualized management based on disease severity, gestational age, and maternal-fetal risks. Close monitoring, supportive care, and a multidisciplinary approach are essential for optimizing outcomes in this rare and complex clinical scenario.

Central nervous system involvement of chronic lymphocytic leukaemia: A rare case report

Central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL) is unfamiliar. The diagnosis is delayed commonly, because of underdiagnosis or subclinical symptoms. We describe a 80-year-old woman with a previous diagnosis of CLL who presented to the emergency service with tonic clonic seizure. The new therapies, eg, ibrutinib and venetoclax, can be effective treatment strategies for CLL with CNS involvement. In our case, treatment with ibrutinib led to a resolution of the cerebralspinal fluid (CSF) neoplastic infiltration, but the patient died afterwards.

Unmutated IGHV at diagnosis in patients with early stage CLL independently predicts for shorter follow-up time to first treatment (TTFT)

The mutational status of the IGHV gene is routinely assessed in patients with chronic lymphocytic leukaemia (CLL), since it is both prognostic of clinical outcome and predictive of response to treatment. This study evaluates the IGHV mutational status, assessed in newly diagnosed CLL patients, as a stand-alone predictor of time to first treatment (TTFT). We analysed the data of 236 CLL patients, diagnosed at our centre between January 2004 and September 2020, with a minimum follow-up period of 3.0 years, Binet A-B and Rai 0-II stages. IGHV was unmutated in 38.1 % and mutated in 61.9 % of cases. The univariate analysis showed a statistically significant difference (p < 0.001) in TTFT based on unmutated (85.2 % at 14 years, 95 % CI = 63.3–94.5 %) or mutated (41.3 % at 14 years, 95 % CI = 29.5–51.8 %) and the need for treatment at 1, 3 and 5 years was of 20.0 % vs 4.1 % (p < 0.001), 42.7 % vs 11.4 % (p < 0.001) and 55.8 % vs 20.0 % (p < 0.001) in unmutated and mutated IGHV patients, respectively. Multivariate analysis confirmed that unmutated IGHV status negatively affects TTFT (p < 0.001), in addition to high-risk genomic aberration (p = 0.025), Rai stage I (p = 0.007) and II (p-value < 0.001). The difference in TTFT based on unmutated or mutated IGHV status remains statistically significant also when considering the subgroups by the genomic aberrations and Rai stages. Our findings suggest that, with the single analysis of the IGHV mutational status at CLL diagnosis, along with clinical and laboratory data, and without karyotype and TP53 data, clinicians will have prognostic and predictive indications for the first clinical treatment and appropriate follow-up of patients.

Unveiling a low-hanging fruit: Single-center study on secondary immunodeficiency in newly diagnosed chronic lymphocytic leukemia and multiple myeloma.

e23215 Background: Infectious complications are the leading cause of morbidity and mortality in patients with chronic lymphocytic leukemia(CLL) and multiple myeloma(MM). Despite recognized risks, evaluation of immune function occurs inconsistently. Our retrospective study evaluated practice patterns for assessing secondary immunodeficiency (SID) in newly diagnosed CLL and MM patients. Our aim is to identify areas for improvement to guide future prospective studies. Methods: We analyzed various immune parameters in newly diagnosed CLL and MM patients at Rochester Regional Health, Rochester, NY, focusing on the first six months of their clinical course, with descriptive data analysis. Results: Conclusions: Current infection prevention guidelines for newly diagnosed CLL and MM patients lack robust evidence. Despite our study’s inherent limitations (small, retrospective, single-center), based on our clinical experience, we propose the following recommendations: Complete SID assessment in all new diagnoses of CLL and MM, and this should include not only Ig levels but also vaccine response. If found to have abnormal SID evaluation, consider prophylactic antibiotics and Ig replacement, and consider reevaluation when appropriate to better define the duration of immunoparesis. Consider short-term Ig replacement (irrespective of IgG levels) and antibacterial prophylaxis for all newly diagnosed MM patients due to high infection risk during the initial six months. A thorough immune evaluation is non-invasive and low-cost, yet it can reveal clinically significant immune dysfunction, potentially influencing management in CLL and MM. Consequently, we hope our study will prompt the development of prospective, randomized studies to systematically evaluate these recommendations. [Table: see text]

#2991 Two cases of chronic lymphocytic leukemia associated immunotactoid glomerulopathy: variable clinical presentation, close hematological collaboration

Abstract Background and Aims Immunotactoid glomerulopathy (ITG) is a very rare disease, observable in less than 0.1% of native kidney biopsy samples. It is most often associated with hematological diseases. We confirmed ITG in two cases among our 850 kidney biopsy patients in the past 9 years. In both patients, chronic lymphocytic leukemia (CLL) was the underlying cause. Method Case 1, a 56-year-old man was admitted due to severely increased proteinuria (2 g/day) with preserved renal function, while case 2, a 57-year-old-man was referred with rapidly decreasing eGFR (20 ml/min/1.73m2) with nephrotic syndrome (serum albumin level was 24 g/l). In case 1, no previous history of hematological disease was known, in case 2, CLL - that did not require treatment - was diagnosed half a year before admission. He still had no kidney involvement even 3 months after the CLL diagnosis. We performed kidney biopsy. Light microscopy revealed mesangial proliferative-atypical membranous pattern in case 1, and membranoproliferative pattern in case 2. Immunofluorescence microscopy showed IgG1-lambda deposition, electron microscopy confirmed the organised deposits, microtubular structures with a diameter of 44 nanometers in both cases. Neither monoclonal gammopathy nor systemic immune disease was confirmed. In case 2, low titer ANA positivity, low C3 and high anti-C1q antibody titer was detected, lupus nephritis was ruled out. Previously, lymphocyte count was slightly increased in case 1, CLL was confirmed after kidney biopsy. The immunoglobulin heavy chain variable region gene somatic hypermutation status was borderline in case 1, while in the other case it was unmutated. Fluorescein in situ hybridisation revealed trisomy 12 in both cases. In case 1, chemotherapy was not used due to Rai stage 0, and with appropriate antihypertensive treatment, we could preserve kidney function, and proteinuria was persistently low (below 1 g/day). In case 2, due to Rai stage 1, and progressive renal and lymph node involvement, immunochemotherapy was started (obinutuzumab-venetoclax). Three months later eGFR stabilized at 27 ml/min/1.73 m2, proteinuria decreased below 1 g/day, the C3 level normalized. Conclusion ITG can develop in the early stages of CLL, but it can also indicate CLL progression. The light microscopy histological pattern and, in parallel, the clinical appearance can be of varying severity. Immunochemotherapy resulting reduction of CLL tumor burden and cessation of complement damage, both play a role of improving renal status. Our cases also draw attention to the need for close collaboration with hematologists.

Evaluation of Immunophenotypic Markers in Diagnosis and Prognosis of Atypical Chronic Lymphocytic Leukemia

Abstract: BACKGROUND: Atypical chronic lymphocytic leukemia diagnosis (aCLL) constitutes of monoclonal B lymphocytes of more than 5000 with unique morphological and immunophenotypic features different from classical or typical CLL. By immunophenotyping, aCLL is differentiated from typical CLL in the negative expression of either one or two immunophenotypic markers, mostly CD23 and/or CD5, provided that the patient does not have the diagnostic criteria of any other lymphoid neoplasm. aCLL patients are usually presented clinically in an aggressive manner and have worse outcomes compared to classic CLL. MATERIALS AND METHODS: This cross-sectional study includes 36 patients diagnosed as aCLL compared to 36 patients diagnosed as typical CLL. Diagnosis depends on blood film morphology and immunophenotyping by 8-color flow cytometry, the markers that are used for diagnosis depend on Matutes scoring system of CLL with the addition of CD200 and CD43, in addition to prognostic markers CD38 and CD305. The clinical staging system was applied, and the patients were divided into low-, intermediate-, and high-risk groups. Follow-up program for 6–12 months with evaluation of their hematological and clinical response and assessment of their remission state as was instituted in the hematological center. RESULTS: CD5 and CD23 are negative in 16.6% and 33.3% of aCLL patients, respectively, whereas CD200 and CD43 are positively expressed in 100% and 83.33% of aCLL patients, respectively, co-expression percentage of both markers in 83.33%. aCLL cases were commonly presented with high-risk group and usually have markers that are linked to poor prognosis, including negative expression of CD305 in 83.3% and positive CD38 expression in 75% of cases and only 5.56% of patients achieved remission state. CONCLUSIONS: aCLL is characterized by immunophenotypic differences in comparison to typical CLL. A definitive diagnosis needs additional markers, mainly CD200 and CD43; the prognosis of aCLL is worse than classical CLL.

MiR-155 and miR-223 as markers of biological and clinical features of chronic lymphocytic leukemia

Introduction. Chronic lymphocytic leukemia (CLL) is a disease characterized by large individual differences both in the clinical course and in molecular patterns of expression of genes and regulatory RNAs, which can influence pathological changes. The involvement of regulatory microRNAs miR-155 and miR-223 in the pathogenesis of CLL is fairly well known, but there is insufficient information about possible fluctuations in the expression of miR-155 and miR-223 depending on the time course of pathology development and on parameters of medical treatment. Purpose – to investigate the expression of miR-155 and miR-223 in patients having CLL with different biological and clinical features and different characteristics of treatment in terms of peripheral-blood substrates (plasma, lymphocytes, and extracellular vesicles) and bone marrow. Material and Methods. This work involved samples of peripheral blood and bone marrow from 38 patients with a diagnosis of CLL from the City Hematology Center at the government-funded healthcare institution (Novosibirsk Oblast) City Clinical Hospital No. 2 from the years 2016 to 2017. Assessment of miR-155 and miR-223 expressions was carried out by reverse-transcription real-time PCR according to the TaqMan principle. Significance of differences between groups was evaluated either by the nonparametric Mann–Whitney test or by the nonparametric Kruskal–Wallis test with subsequent pairwise comparisons via the Mann–Whitney test. Results. High variation of the analyzed parameters was found. The expression levels of miR-155 and miR-223 in microvesicles of patients with unfavorable chromosomal anomalies were lower than those in patients with the chromosomal aberrations (or the normal karyotype) associated with a moderate effect on CLL prognosis. The expression level of miR-223 in peripheral blood lymphocytes of untreated patients with CLL was higher than that observed in treated patients. Conclusion. differences in the expression levels of miR-155 and miR-223 were identified depending on chromosomal aberrations and polychemotherapy. Our preliminary results will provide the basis for future larger studies on levels of microRNAs in CLL patients having specific features of the development, clinical course, and treatment of the disease.

The Looming Cancer: A Qualitative Study on the Experience of Living with Chronic Lymphocytic Leukemia (CLL) before the Initiation of Treatment

Purpose. This study aimed to study the challenges and ways of coping with living with chronic lymphocytic leukemia (CLL) before the initiation of treatment. Methods. Semistructured interviews were carried out with 8 people living with CLL (4 males and 4 females) who had never received any treatment. Interpretative phenomenological analysis was utilized for the analysis of the data. Results. The following three themes were developed: (1) “Still waters run deep” highlights the contrast between living with minimal symptoms while experiencing high anxiety for the future, (2) “Surviving uncertainty” portrays participants’ supportive networks, communication challenges, and internal coping mechanisms to face the threatening overtones of CLL, and (3) “Turning over a new leaf” delineates participants’ realization of life’s finiteness and the way this acts as a nudge for psychological growth. Conclusion. Despite the limited physical discomfort, the CLL diagnosis and the watch-and-wait phase bring about psychological distress, which drives meaning-making efforts and an array of coping mechanisms, potentially leading to posttraumatic growth processes for people living with CLL.

Outcomes with ibrutinib in patients with chronic lymphocytic leukaemia: Results from the German multicentre REALITY study.

To assess treatment adherence, effectiveness and safety outcomes of patients with chronic lymphocytic leukaemia (CLL) receiving ibrutinib in a real-world setting. Patients enrolled in REALITY were ≥18 years with a confirmed diagnosis of CLL and were receiving ibrutinib as a first-line (1L), 2L or ≥3L therapy. Treatment retention, adherence, progression-free survival (PFS), overall survival (OS) and time to next therapy were assessed at 1 and 2 years overall, by typology and by cytogenetic subgroups. PFS and OS were analysed using Kaplan-Meier methods. Exactly 302 patients were enrolled across 57 sites in Germany, from January 2017 to July 2021. One-year retention rates were 69.9% overall (primary endpoint), 77.9% for 1L patients, and 77.6%/78.8% for high-risk patients with del17p/TP53. At 2 years, PFS/OS rates were 77.8%/90.7% overall (1L, 82.7%/90.4%), and were consistent across cytogenetic subgroups. PFS rates were higher for 1L versus ≥3L patients. Patients with the low-acceptance/low-control typology at baseline were less likely to retain treatment at 1 year versus the high-acceptance/high-control typology. No new safety signals were observed. The REALITY study provides further evidence of the effectiveness and safety of ibrutinib in patients with CLL in a real-world setting, particularly in earlier treatment lines.

How receptor tyrosine kinase-like orphan receptor 1 meets its partners in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in western societies, recognized by clinical and molecular heterogeneity. Despite the success of targeted therapies, acquired resistance remains a challenge for relapsed and refractory CLL, as a consequence of mutations in the target or the upregulation of other survival pathways leading to the progression of the disease. Research on proteins that can trigger such pathways may define novel therapies for a successful outcome in CLL such as the receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 is a signaling receptor for Wnt5a, with an important role during embryogenesis. The aberrant expression on CLL cells and several types of tumors, is involved in cell proliferation, survival, migration as well as drug resistance. Antibody-based immunotherapies and small-molecule compounds emerged to target ROR1 in preclinical and clinical studies. Efforts have been made to identify new prognostic markers having predictive value to refine and increase the detection and management of CLL. ROR1 can be considered as an attractive target for CLL diagnosis, prognosis, and treatment. It can be clinically effective alone and/or in combination with current approved agents. In this review, we summarize the scientific achievements in targeting ROR1 for CLL diagnosis, prognosis, and treatment.

Evaluation of the Findings of Peripheral Blood Smear, Bone Marrow Aspiration and Biopsy, Iron Storage, and Immunophenotype in Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults with various signs, symptoms, and types of progression. In this study, we have investigated the frequency and correlation of laboratory findings including peripheral blood smear, bone marrow aspiration and biopsy, and cellular immunophenotyping in CLL patients. In this cross-sectional and retrospective study, the laboratory information of all 161 patients with definite diagnoses of CLL was extracted, and the frequency and correlation between different laboratory data were analyzed by descriptive statistics methods and Jamovi software version 2022. Demographic factors such as age and gender, and laboratory factors such as anemia, thrombocytopenia, white blood cell count, percentage of lymphocytes, and patterns of bone marrow involvement were evaluated for 161 patients. There was a significant relationship between the bone marrow iron storage and the percentage of FMC7 marker expression with the percentage of atypical lymphocytes in the peripheral blood. Chronic lymphocytic leukemia, a prevalent form of leukemia associated with substantial mortality and morbidity, can be detected through a range of diagnostic techniques. Analyzing the results of these diagnostic tests and examining the prevalence of these indicators in patients afflicted with the condition can prove highly beneficial for prompt disease diagnosis, and prognosis determination among affected individuals.

Prediction of severe infections in chronic lymphocytic leukemia: a simple risk score to stratify patients at diagnosis

Chronic Lymphocytic Leukemia (CLL) is well-known for increasing susceptibility to infections. Factors such as immune dysregulation, IGHV status, hypogammaglobulinemia, and patient comorbidity and treatment, contribute to higher infection rates and mortality. However, the impact of hypogammaglobulinemia on infection rates is controversial. We aimed to identify clinical and biological parameters linked to the risk of severe infectious events. Additionally, we set up a straightforward risk infection score to stratify CLL patients at diagnosis, thereby enabling the development of suitable infection prevention strategies. We retrospectively evaluated 210 unselected CLL patients diagnosed between 1988 and 2018. This evaluation encompassed demographics, Binet stage, immunoglobulin (Ig) levels, treatment history, comorbidities, and IGHV mutational status at diagnosis. The frequency and severity of infectious events were recorded. Analysis revealed that age, IGHV mutational status, Binet stage, and hypogammaglobulinemia were statistically associated with the Time to First Infection (TTFI) in univariate and multivariate analyses. Using hazard ratios from the multivariate analysis, we finally devised a risk scoring system that integrated age, IGHV mutational status, immunoglobulin levels, and Binet stage to stratify patients at diagnosis based on their specific infection risk. In our cohort, disease progression and infections were the leading cause of death. These findings pointed out the clinical need for a screening process strategic for defining infectious risk at the time of CLL diagnosis, with a significant enhancement in the clinical management of these patients.

Expression of ZAP 70 in Chronic Lymphocytic Leukemia (CLL) and its Correlation with Clinical Stages

Objective: To ascertain the levels of ZAP-70 expression within the context of Chronic Lymphocytic Leukemia (CLL) patients and to subsequently analyze the potential correlations between ZAP-70 expression and the clinical staging of the disease. Study Design &amp; Setting: Cross-sectional, descriptive study. Department of Hematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from July 2021 to December 2021. Methodology: We included 73 CLL patients of various ages and both genders. and patients having lymphoproliferative disorders other than CLL were excluded. Sysmex XN-3000 was used to do complete blood counts. Diagnosis of CLL was confirmed immunophenotypically by flow cytometry. Samples were processed by standard methods for ZAP70 analysis. Descriptive statistics were expressed in terms of mean ± standard deviation (SD). A Chi-square test was conducted, with a significance level of p-value =0.05 being considered significant. Results: Among 73 patients, 24 were females (32.9%) and 49 were males (67.1%). Females had a mean age of 69.00±9.47 years, whereas males had a mean age of 65.73±11.12 years. ZAP-70 expression was positive in 8 (11%) and negative in 65 (89.0%) cases. The expression of ZAP-70 in CLL and its correlation with Binet Stages was significant (p=0.002). ZAP- 70 expression in males and females showed no significant difference (p 0.059). ZAP-70 analysis showed no significant difference in patients with age more than 60 years from = 60 years of age (p= 0.275) Conclusion: ZAP-70 gene expression should be used in routine laboratory settings and can be correlated with the clinical stages of CLL

Intraocular sarcoid-like reaction in patients with chronic lymphocytic leukemia

ObjectifVérifier la fréquence de survenue et les caractéristiques cliniques de la réaction sarcoïdosique (SLR, pour sarcoid-like reaction) intraoculaire paranéoplasique dans la leucémie lymphoïde chronique (LLC). MéthodesExamen rétrospectif des dossiers de patients présentant une LLC entre le 1er janvier 1980 et le 31 décembre 2020. On a procédé à la recherche d'examens oculaires à l'aide de 22 mots clés évoquant une SLR, et les dossiers ont été vérifiés manuellement. RésultatsSur les 4209 patients uniques qui présentaient une LLC, 1021 (24 %) avaient subi au moins 1 examen oculaire selon les notes consignées à leur dossier, et au moins 1 mot clé figurait dans la description des résultats de l'examen oculaire de 324 (8 %) patients. Après vérification manuelle des dossiers, une SLR a été évoquée chez 12 patients (< 1 %) : 7 patients présentaient une SLR probable à caractéristiques typiques et 1 patient, une SLR possible sans caractéristique classique; chez les 4 autres, la SLR était soupçonnée, mais moins probable. Tous les patients qui ont eu une SLR probable ou possible (n = 8) étaient de race blanche, et la moitié (n = 4) étaient de sexe masculin. La SLR intraoculaire a été diagnostiquée en moyenne 49,7 mois après le diagnostic de LLC (n = 7) ou 1 mois avant le diagnostic de LLC (n = 1). Il s'agissait d'une atteinte bilatérale chez 5 patients. On comptait en tout 13 yeux touchés, et l'acuité visuelle moyenne au moment de l'examen initial était de 20/50 sur l’échelle de Snellen. À l'examen initial, les caractéristiques suivantes ont été fréquemment observées : cellules vitreuses (n = 13), cellules de la chambre antérieure (n = 10), précipités kératiques (n = 9), synéchies postérieures (n = 6), lésions choriorétiniennes (n = 5) et flou du vitré (n = 5). Le traitement a reposé sur les corticostéroïdes topiques seuls (n = 5), avec l'administration sous-ténonienne de corticostéroïdes (n = 1) ou d'immunosuppresseurs d’épargne cortisonique (n = 1), ou sur les corticostéroïdes oraux seuls (n = 1). Après un suivi moyen de 19,8 mois, l'acuité visuelle finale moyenne était de 20/30. ConclusionLa SLR intraoculaire touche moins de 1 % des patients atteints de LLC et doit figurer sur la liste des diagnostics différentiels des troubles oculaires en présence de LLC. L'administration de corticostéroïdes permet une prise en charge efficace de la plupart des patients.

IMMUNOPHENOTYPE OF LEUKEMIC CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS WITH NOTCH1 AND SF3B1 GENE MUTATIONS.

The typical chronic lymphocytic leukemia (CLL) immunophenotype is vital for diagnosis, but the expression of some antigens varies and has prognostic value. There are data that reduced CD20 expression is associated with NOTCH1 and SF3B1 gene mutations. To determine a high-risk group of CLL patients for prediction of unfavorable NOTCH1 and SF3B1 gene mutations based on immunophenotyping of leukemic cells. Flow cytometric and molecular-genetic analysis (mutations of NOTCH1, SF3B1, and TP53 genes using the polymerase chain reaction followed by direct sequencing) was performed in a group of 86 previously untreated CLL patients. The immunophenotype of leukemic cells of all examined patients met the criteria of CLL diagnosis. NOTCH1 gene mutations were found in 21 patients (24.4%), and SF3B1 gene mutations - in 7 patients (8.1%). There were no TP53 gene mutations among the examined patients. A decreased number of CD20+CD5+ cells and a downward trend in the relative index of mean fluorescence intensity (iMFI) of CD20+ cells were found in patients with NOTCH1 and SF3B1 gene mutations. Based on the iMFI level (higher and/or lower than 3.0) and the number of CD20+CD5+ cells among all B-cells (higher and/or lower than 50%), we distinguished CLL cases with low and relatively high levels of CD20 antigen expression. Using ROC analysis and the parameter of low CD20 antigen expression, we could predict the presence of NOTCH1 and SF3B1 gene mutations in 73.3 ± 0.06% of patients (p = 0.001). The risk of NOTCH1 and SF3B1 gene mutations in cases with low CD20 antigen expression was 6.96 (95% CI = 2.53-19.18; p = 0.0001). The revealed regularities were statistically significant for patients in whom the diagnosis was established in all Binet - Rai stages except A0-AI. Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.