scholarly journals Colonic Involvement in a Patient with Chronic Lymphocytic Leukaemia

2008 ◽  
Vol 2008 ◽  
pp. 1-4 ◽  
Author(s):  
P. E. T. Arkkila ◽  
H. Nuutinen ◽  
F. Ebeling ◽  
E. Elonen ◽  
P. Kärkkäinen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Lymphocytic Leukemia ◽  
Diagnostic Evaluation ◽  
Bone Marrow Infiltration ◽  
Macroscopic Finding ◽  
Colonic Involvement

Various gastrointestinal infiltrations have been described in patients with chronic lymphocytic leukaemia (CLL). Here, we report a 69-year-old man with CLL and anaemia in whom the macroscopic finding of colonoscopy was normal, but the histological specimens revealed lymphocytic leukemia in ileum and in colon. If a CLL patient has any symptoms suggesting a possible GI manifestation of the haematologic disease or anaemia not explained by bone marrow infiltration or hemolysis, the diagnostic evaluation should include endoscopies with adequate biopsies.

Prognostic Value of ZAP-70 Expression Detected by Immunohistochemistry on Bone Marrow Biopsies in Early Phase Chronic Lymphocytic Leukaemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4800-4800
Author(s):  
Achille Ambrosetti ◽  
Roberta Zanotti ◽  
Marco Chilosi ◽  
Flavia Zanetti ◽  
Maurizio Lestani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Methodological Approach ◽  
Bone Marrow Infiltration ◽  
Leukemic Cells ◽  
Immunohistochemical Method ◽  
Bone Marrow Biopsies ◽  
Cytoplasmic Expression ◽  
Binet Stage

Abstract New biological prognostic factors have been developed over the last years with the aim of predicting at presentation the heterogeneous clinical course of B chronic lymphocytic leukaemia (B-CLL) and of planning a risk-adapted treatment strategy. Among them ZAP-70 expression on leukemic cells as evaluated by molecular analysis or flow cytometry, initially proposed as surrogate of IgVH mutational status, appears a strong prognostic marker in B-CLL. However the optimal methodological approach to immunophenotipical demonstration of ZAP-70 expression as still matter of debate. We evaluated the cytoplasmic expression of ZAP-70 protein in leukemic cells by immunohistochemical method on bone marrow trephine biopsies taken at diagnosis of 84 patients with B-CLL. We used a mouse anti-human monoclonal antibody to ZAP-70 (clone 2F3.2, 1/200, Upstate, Lake Placid NY) with a polymeric labelling two-step method (Dako cytomation EnVision+, HRP). The results were correlated with age, sex, Binet stage, pattern of bone marrow infiltration, survival and clinical outcome. They were 54 males (64%), aged 34 to 80 years (median 62.5). At presentation 69 (82%) were Binet stage A, 9 (11%) stage B and 6 (7%) stage C. Among the 60 survivors, the median follow-up period from diagnosis was 78.5 months (range 22 – 236 months) Thirty-nine cases (46%) of B-CLL patients had cytoplasmic expression of ZAP-70. This group of patients presented higher percentage of advanced Binet stage (B–C) (p= 0.001). The ZAP-70 positivity was significantly related to inferior OS (55% vs 90% at 7 years)(HR 4.67 CI 1.95–11.14) and PFS (15% vs 57% at 7 years) (HR 5.52 CI 2.57–11.86), confirmed in multivariate analysis. ZAP-70 expression was correlated to poorer outcome also when we evaluated only the 69 stage A patients and the 56 cases with non-diffuse bone marrow infiltration, whereas in patients with diffuse pattern ZAP-70 expression had no prognostic significance. In conclusion, immunohistological detection of ZAP-70 on bone marrow samples at diagnosis appears a useful methodological approach to identify patients with different prognosis in B-CLL.

Chronic lymphocytic leukaemia

2020 ◽  
pp. 5302-5310
Author(s):  
Clive S. Zent ◽  
Aaron Polliack
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Lymphocytic Leukaemia ◽  
Bone Marrow Failure ◽  
Curative Therapy ◽  
Symptomatic Disease ◽  
Autoimmune Cytopenias

Chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma is the most prevalent lymphoid neoplasm in Europe and North America. The ‘cell of origin’ is a mature B lymphocyte with a rearranged immunoglobulin gene. CLL cells express modest amounts of surface immunoglobulin, and are characterized by defective apoptosis. The cause of CLL is unknown. Most patients show no specific clinical features of disease and are diagnosed during evaluation of an incidental finding of peripheral blood lymphocytosis, lymphadenopathy, or splenomegaly. A small percentage of patients (<10%) present with symptomatic disease resulting from (1) tissue accumulation of lymphocytes such as disfiguring lymphadenopathy, splenomegaly with abdominal discomfort, profound fatigue, drenching night sweats, weight loss, and fever; or (2) manifestations of marrow failure with cytopenias including anaemia and thrombocytopenia. All CLL patients have an increased risk of infection, autoimmune cytopenias, and second haematological (e.g. diffuse large B-cell lymphoma) and nonhaematological malignancies. Diagnosis is usually made by analysis of the immunophenotype of the monoclonal circulating cells in the peripheral blood. In patients with the small lymphocytic variant of CLL without a detectable circulating monoclonal B-cell population, the diagnosis is made using tissue from the bone marrow, lymph nodes, or spleen. Treatment—there is no standard curative therapy and patients should not be treated until they have progressive and symptomatic disease or develop anaemia or thrombocytopenia due to bone marrow failure. If a decision is made to treat, then the best initial treatment should be given, based on evaluation of the patient’s disease characteristics with specific attention to the integrity of TP53 (coding for p53) and patient fitness.

The Prognostic Significance of Autoimmune Cytopenias in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2361-2361
Author(s):  
Carol Moreno ◽  
Kate E Hodgson ◽  
Pau Abrisqueta ◽  
Gerardo Ferrer ◽  
Montse Elena ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Stage ◽  
Lymphocytic Leukemia ◽  
Bone Marrow Infiltration ◽  
Clinical Staging ◽  
Immune Disease ◽  
Advanced Clinical Stage ◽  
Positive Direct ◽  
Autoimmune Cytopenia

Abstract Abstract 2361 Poster Board II-338 Clinical staging systems are the backbone for assessing prognosis in patients with chronic lymphocytic leukemia (CLL). Clinical stages, however, are assigned without taking into consideration the mechanisms of the disease. In this regard, the prognosis of patients with advanced (Binet C, Rai III, IV) stage due to immune cytopenia is controversial. To address the prognosis of patients with CLL in advanced clinical stage due to immune mechanisms, we studied two groups of patients with and without autoimmune cytopenia. The first group consisted of 62 patients (39 men, median age 65 yrs; range 33-89) with advanced stage due to autoimmune cytopenia (stage C “immune”). Autoimmune hemolytic anemia (AIHA) was defined as a hemoglobin level <10g/dL and either a positive direct antiglobulin test (n=37) or indirect signs of hemolysis including a high reticulocyte count, low haptoglobin levels, increased LDH and bilirrubin levels (n=7). Immune thrombocytopenia (ITP) was defined as a platelet count < 100.000/mm3 with normal megakaryocytes in bone marrow or no reticulocytopenia, no enlarged spleen and no chemotherapy within the last month from study entry (n=18). The control group included 96 patients (59 men, median age 68 yrs; range 28-90) with stage C disease with no signs of immune-mediated cytopenia. Demographics, clinical characteristics and duration of follow-up were similar in both groups. When considered from the time of diagnosis, patients with stage C “immune” disease had a significantly better survival than those in stage C due to bone marrow infiltration (median survivals: 89 months vs. 45 months; p=0.04). In contrast, the prognosis of 12 patients who developed immune cytopenia during the course of the disease was not different from that of 42 patients who had progressed to stage C with no evidence of autoimmunity, neither when considered from the time of diagnosis (median survivals: 110 months vs. 101 months; p=0.71) nor from the point at which cytopenia (either autoimmune or infiltrative in origin), was detected (median survivals: 51 months vs. 63 months; p=0.102). When the analysis was restricted to the 62 patients with autoimmune cytopenia, no significant differences in survival were observed according to the time at which the autoimmune disorder was detected, i.e. at diagnosis or during the course of the disease (median survivals: 89 months vs.103 months; p=0.38). Of note, 11 out of the 18 patients with stage C “immune” disease at diagnosis responded to corticosteroids and, as a result, switched to stage A, whereas only 8 out of 53 patients with stage C due to bone marrow infiltration had a similar response to chemotherapy. In summary, this study shows that the outcome of patients with CLL who present with advanced clinical stage differs according to the origin of the cytopenia (i.e., immune vs. infiltrative) and emphasizes the importance of determining the origin of the cytopenia when evaluating patients with CLL and “advanced” clinical stage. These results also make a case for including a stage C “immune” group in the prognostic categorization of patients with CLL. Disclosures: No relevant conflicts of interest to declare.

Characterization of MYD88 mutated Lymphoplasmacytic Lymphoma in Comparison to MYD88 mutated Chronic Lymphocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 132-132
Author(s):  
Constance Regina Baer ◽  
Frank Dicker ◽  
Wolfgang Kern ◽  
Torsten Haferlach ◽  
Claudia Haferlach
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Lymphocytic Leukemia ◽  
Bone Marrow Infiltration ◽  
Multiparameter Flow Cytometry ◽  
Employment Equity ◽  
Cytogenetic Aberration ◽  
Highly Sensitive ◽  
Equity Ownership

Abstract Introduction: MYD88 (Myeloid Differentiation Primary Response 88) mutations are the most common genetic aberration in Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (LPL). Since the initial description of MYD88 mutations in LPL, the detection has gained great importance in diagnosing the disease. However, in some patients with other B cell malignancies, including chronic lymphocytic leukemia (CLL), MYD88 mutations are detectable. Aim: We describe the molecular and cytogenetic profile of MYD88 mutated LPL in comparison to CLL, in order to identify aberration patterns potentially useful for diagnostic purposes. Patients and Methods: We analyzed bone marrow samples of 78 LPL patients for MYD88 by highly sensitive allele specific PCR (ASP) for the L265P mutation and by next-generation sequencing (NGS) for MYD88 and CXCR4 (Chemokine (C-X-C Motif) Receptor 4) mutations. For CLL, 784 blood or bone marrow samples were sequenced for MYD88 (by NGS), IGHV, TP53, NOTCH1 and SF3B1 by Sanger or NGS as well as the MYD88 mutated CLL cases for CXCR4. For all samples, cytogenetic and multiparameter flow cytometry data was available. Results: In LPL, 68/78 patients (87%) harbored a MYD88 mutation. In 13 cases with low bone marrow infiltration (median: 3%; range: 1-6%), the MYD88 mutation was detected by ASP only and not by NGS. However, one case was identified by NGS only because of a non-L265P mutation, which cannot be detected by ASP (1/68; 1%). In contrast, in CLL only 17/784 (2%) carried a MYD88 mutation. Interestingly, 5/17 (29%) were non-L265P mutations. Of the MYD88 mutated LPL, 17/68 (25%) carried a genetic lesion in the C-terminal domain of CXCR4. In contrast to MYD88, the mutation spectrum of CXCR4 was much broader including non-sense mutations at amino acid S338 (10/18) but also frame shifts resulting in loss of regulatory serine residues. One patient had two independent CXCR4 mutations (S338* and S341Pfs*25). The mean bone marrow infiltration by flow cytometry was 14% and 9% in the CXCR4 mutated and unmuted subsets, respectively (p=0.17). Besides molecular genetic aberrations, 25% (17/68) of MYD88 mutated LPL cases carried cytogenetic aberration. The most frequent cytogenetic aberration in the MYD88 positive LPL was the deletion of 6q (10/68; 15%). Other recurrent cytogenetic abnormalities were gains of 4q (n=3), 8q (n=2), and 12q (n=4), as well as loss of 11q (n=4), 13q (n=2) and 17p (n=3). In the MYD88 unmutated group, we did neither identify any CXCR4 mutation nor any del(6q), suggesting different genetic driver events in this LPL subcohort. Importantly, in the MYD88 positive CLL cohort, cytogenetic analysis did not reveal any patient with del(6q). Instead, del(13q)(q14) was the most prevalent cytogenetic aberration (12/17; 71%). Neither 11q deletions nor 17p deletions were detected. All MYD88 positive CLL had a mutated IGHV status (MYD88 unmutated CLL: 453/767; 59%; P<0.001). The TP53, NOTCH1 and SF3B1 mutational landscape did not reveal any differences between the MYD88 mutated and unmutated cohort. Finally, CXCR4 mutations were present in none of 15 analyzed MYD88 mutated CLL cases. Conclusion: Besides multiparameter flow cytometry, MYD88 mutations are the most powerful tool in the diagnosis of LPL. MYD88 mutated LPL are characterized by a high frequency of CXCR4 mutations and del(6q), while MYD88 unmutated LPLs are associated with a different pattern of genetic abnormalities. MYD88 mutated CLL is a distinct CLL subset associated with mutated IGHV status, a high frequency of 13q deletions and low frequencies of 11q and 17p deletions. MYD88 mutated CLL differs from MYD88 mutated LPL with respect to the pattern of MYD88 mutations, cytogenetic aberrations and the absence of CXCR4 mutations. Highly sensitive ASP allows the L265P mutation detection even in LPL cases with very low bone marrow infiltration; whereas highly sensitive NGS assay are best applicable for detection of more heterogenic MYD88 mutations in CLL or CXCR mutations in LPL. Thus, an integrated molecular and cytogenetic approach allows the characterization of disease specific genetic patterns and should be analyzed for its clinical impact. Disclosures Baer: MLL Munich Leukemia Laboratory: Employment. Dicker:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

CD13 Expression in B-Cell Chronic Lymphocytic Leukemia is Associated with the Pattern of Bone Marrow Infiltration

1992 ◽  
Vol 6 (3) ◽  
pp. 209-218 ◽  
Author(s):  
Antonio Pinto ◽  
Vittorina Zagonel ◽  
Antonino Carbone ◽  
Diego Serraino ◽  
Giuseppe Marotta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Bone Marrow Infiltration ◽  
Cell Chronic Lymphocytic Leukemia
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