Atypical “accelerated” chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica

Yavorkovsky, Leonid L.

doi:10.1002/cnr2.1601

Cited by 4 publications

(2 citation statements)

References 8 publications

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“…In such circumstances, practitioners often question whether a DLBCL was missed as a result of sampling bias (i.e., either a core-needle biopsy or an excisional biopsy of one node in a nodal conglomerate was obtained). These “grey zone” cases have been described since 1988 and have more recently been referred to as histologically accelerated CLL (HAC) [ 28 , 29 , 30 ]. HAC is not recognized by the WHO classification and lacks formal diagnostic criteria.…”

Section: Diagnostic Evaluationmentioning

confidence: 99%

Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era

Briski

Taylor

2023

Cancers

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Richter Transformation (RT) refers to the development of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). While many variants of RT are recognized, diffuse large B-cell lymphoma (RT-DLBCL) is the most common (80%), followed by Hodgkin’s lymphoma (RT-HL, 19%). Diagnosis is based upon histologic evaluation of clinically suspicious lymph nodes. Positron emission tomography (PET) may be used to select the node of interest for biopsy. Although clonality testing is not a prerequisite of RT diagnosis, it has significant implications for survival. Clonally related DLBCL carries the worst prognosis with a median overall survival (OS) of less than one year in the era of combination chemotherapies with or without anti-CD20 antibodies. Prognosis has improved with the use of stem cell transplant and newer agents such as targeted therapy and newer forms of immunotherapy. Consideration of a clinical trial is encouraged. This review describes our current understanding of RT and focuses on treatment of RT-DLBCL, including clinical trials in progress and new therapies in development. We also report an illustrative example of a patient with clonally related DLBCL who survived two years after diagnosis without the use of combination chemotherapy.

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Section: Diagnostic Evaluationmentioning

confidence: 99%

Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era

Briski

Taylor

2023

Cancers

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“…Data are very limited regarding the role of targeted therapies for A-CLL. Successful treatment of A-CLL has been reported with ibrutinib [11, 12] and acalabrutinib [13]. One case report of leukemia cutis in A-CLL was successfully treated with venetoclax and rituximab [14].…”

Section: Accelerated Chronic Lymphocytic Leukemiamentioning

confidence: 99%

Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents

Levy Yurkovski,

Tadmor

2023

Acta Haematol

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Background: Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to “accelerated CLL” (A-CLL) or to “Richter transformation” (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations. Summary: A-CLL is a rare and underdiagnosed entity that probably stands in the “gray zone” between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials. Key Messages: The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of “unmet need” and require further studies to identify the best diagnostic approach and a more effective treatment.

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Atypical “accelerated” chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica

Yavorkovsky

2022

Cancer Reports

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Background The “accelerated” chronic lymphocytic leukemia (aCLL) is a relatively rare form of CLL progression. The expanded proliferation centers in aCLL have been associated with adverse prognostic features and propensity to more aggressive behavior with shorter survival. Case An atypical case of aCLL with distinct features is described. A 66‐year‐old female presented with a marrow replacing process associated with multiple osseous metastases and trivial lymphadenopathy. Bone biopsy revealed an unspecified low‐grade B cell lymphoproliferative disorder that demonstrated a suboptimal response to standard chemotherapy. Subsequent lymph node biopsy demonstrated findings consisted with aCLL. The distinguishing features of the case were, in addition to bone involvement, the lagging peripheral lymphocytosis and a striking pattern of the chromatin clumping with a prominent “shattered” appearance reminiscent of Pelger‐Huet‐like dysplastic anomaly. A targeted next‐generation sequencing (NGS) assay detected pathogenic mutations in TP53 and SF3B1 . In contrast to chemotherapy, the case demonstrated an excellent response to imbruvica. Conclusion The noted peculiarities could potentially distinguish this case as a novel, rare variant of aCLL.

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Atypical “accelerated” chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica

Cited by 4 publications

References 8 publications

Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era

Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era

Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents

Atypical “accelerated” chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica

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