A matter of debate in chronic lymphocytic leukemia

Caligaris-Cappio, Federico

doi:10.1097/cco.0b013e328348c683

Cited by 17 publications

(9 citation statements)

References 45 publications

(35 reference statements)

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“…Immune thrombocytopenia (ITP) is the second most common and involves antibody-mediated platelet destruction. 12 Pure red cell aplasia (PRCA) and autoimmune granulocytopenia (AIG) are relatively rare and occur in <1% patients. 13 PRCA develops due to an immune-mediated destruction of red cell precursors and manifests as reticulocytopenia and anemia.…”

Section: Epidemiologymentioning

confidence: 99%

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Tsang

2017

Curr Hematol Malig Rep

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Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune complications such as autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia and autoimmune granulocytopenia. It is critical to diagnose cytopenias from these secondary complications of CLL accurately, since prognosis and therapy are substantially different from patients who have cytopenias due to extensive bone marrow infiltration by CLL. The pathogenesis of autoimmune cytopenias in CLL is complex; and involves antigen presentation by CLL cells to polyclonal B-cells resulting in production of autoantibody and alteration of the T-cell milieu tilting the balance in favor of an autoimmune response. Traditional therapy of autoimmune complications in CLL consists of immunosuppression with corticosteroids and/or anti-CD20 monoclonal antibodies. In patients who have a suboptimal response, treating the underlying CLL is generally effective in ameliorating secondary cytopenias. Although novel oral therapies such as ibrutinib, idelalisib and venetoclax have been shown to be extremely effective in the management of CLL; prospective data from larger numbers of patients with longer follow-up are needed prior to recommending their routine use in the management of autoimmune cytopenias in CLL.

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Section: Epidemiologymentioning

confidence: 99%

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Tsang

2017

Curr Hematol Malig Rep

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“… 35 Cytopenias in CLL can result from either bone marrow failure or autoimmune disease. 36 , 37 Two studies showed that CLL patients with +12 have a higher incidence of autoimmune cytopenias than infiltrative cytopenias. 36 , 37 …”

Section: Introductionmentioning

confidence: 99%

Morphological, immunophenotypic, and genetic features of chronic lymphocytic leukemia with trisomy 12: a comprehensive review

2018

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Chronic lymphocytic leukemia is an extremely heterogeneous disease and prognostic factors such as chromosomal abnormalities are important predictors of time to first treatment and survival. Trisomy 12 is the second most frequent aberration detected by fluorescence in situ hybridization at the time of diagnosis (10–25%), and it confers an intermediate prognostic risk, with a median time to first treatment of 33 months and a median overall survival of 114 months. Here, we review the unique morphological, immunophenotypic, and genetic characteristics of patients with chronic lymphocytic leukemia and trisomy 12. These patients carry a significantly higher expression of CD19, CD22, CD20, CD79b, CD24, CD27, CD38, CD49d, sIgM, sIgk, and sIgλ and lower expression of CD43 compared with patients with normal karyotype. Circulating cells show increased expression of the integrins CD11b, CD18, CD29, and ITGB7, and of the adhesion molecule CD323. Patients with chronic lymphocytic leukemia and trisomy 12 frequently have unmutated IGHV, ZAP-70 positivity, and closely homologous stereotyped B-cell receptors. They rarely show TP53 mutations but frequently have NOTCH1 mutations, which can be identified in up to 40% of those with a rapidly progressive clinical course.

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“…During the course of disease, cytopenias have been observed in up to 24% of patients with CLL, resulting from bone marrow failure or autoimmune disease. 33,34 While the diagnosis of autoimmune hemolytic anemia is based on specific laboratory findings, identifying an autoimmune thrombocytopenia can be problematic. 35,36 In our series, bone marrow infiltration was not associated with +12 on MVA, suggesting an autoimmune etiology for the elevated rate of thrombocytopenia that we observed.…”

Section: Discussionmentioning

confidence: 99%

Second Cancers and Richter Transformation Are the Leading Causes of Death in Patients With Trisomy 12 Chronic Lymphocytic Leukemia

Strati

Abruzzo

Wierda

et al. 2015

Clinical Lymphoma Myeloma and Leukemia

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Trisomy 12 (+12) is detected by fluorescence in situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis. In order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12. When compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter Transformation (RT) and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time-to-first-treatment was 38 months and on multivariate analysis (MVA) it was shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA it was shorter in patients who achieved a response other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but on MVA it was shorter in patients with an absolute lymphocyte count >30×109/L or who developed SMN. Eighteen deaths have been observed so far, and RT and SMN were the leading causes of death (3 and 6, respectively). In conclusion, patients with +12 CLL show characteristic clinical and biological features, and may benefit from increased surveillance for second cancers.

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A matter of debate in chronic lymphocytic leukemia

Abstract: Simple-refractory and complex autoimmunity are independent indicators of therapy for CLL. Further, epidemiological and biological studies will help clarifying the prognostic and possibly also the pathogenetic significance of simple autoimmunity.

Cited by 17 publications

References 45 publications

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

A Concise Review of Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

Morphological, immunophenotypic, and genetic features of chronic lymphocytic leukemia with trisomy 12: a comprehensive review

Second Cancers and Richter Transformation Are the Leading Causes of Death in Patients With Trisomy 12 Chronic Lymphocytic Leukemia

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