Richter Syndrome

Condoluci, Adalgisa; Rossi, Davide

doi:10.1007/s11912-020-01001-x

Cited by 23 publications

(15 citation statements)

References 70 publications

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“…Mostly in the literature, and our cohort, these were diffuse large B‐cell lymphoma (DLBCL), with smaller numbers with Hodgkin's lymphoma (HL). Rarely, T‐cell variants have been described, and we included in the RS group T‐cell malignancies of any histology [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

Second primary malignancies in chronic lymphocytic leukaemia: Skin, solid organ, haematological and Richter's syndrome

Shen

Coyle

Kerridge

et al. 2021

eJHaem

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Chronic lymphocytic leukaemia (CLL) is invariably accompanied by some degree of immune failure, and CLL patients have a high rate of second primary malignancy (SPM) compared to the general population. We comprehensively documented the incidence of all forms of SPM including skin cancer (SC), solid organ malignancy (SOM), second haematological malignancy (SHM) and separately Richter's syndrome (RS) across all therapy eras. Among the 517 CLL/small lymphocytic lymphoma (SLL) patients, the overall incidence of SPMs with competing risks was SC 31.07%, SOM 25.99%, SHM 5.19% and RS 7.55%. Of the 216 treated patients, 106 (49.1%) had at least one form of SPM, and 63 of 106 (29.2% of treated patients) developed an SPM 1.5 years (median) after treatment for their CLL. Melanoma accounted for 30.3% of SC. Squamous cell carcinoma (SCC), including eight metastatic SCCs, was 1.8 times more than basal cell carcinoma (BCC), a reversal of the typical BCC:SCC ratio. The most common SOMs were prostate (6.4%) and breast (4.5%). SHM included seven acute myeloid leukaemia (AML) and five myelodysplasia (MDS) of which eight (four AML, four MDS) were therapy‐related. Any SPM occurred in 32.1% of 53 Monoclonal B‐lymphocytosis (MBL) patients. Age‐adjusted standardised rates of SPM (per 100,000) for CLL, MBL and the general Australian population were 2648, 1855 and 486.9, respectively. SPMs are a major health burden with 44.9% of CLL patients with having at least one SPM, and apart from SC, associated with significantly reduced overall survival. Dramatic improvements in CLL treatment and survival have occurred with immunochemotherapy and targeted therapies, but mitigating SPM burden will be important to sustain further progress.

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Section: Methodsmentioning

confidence: 99%

Second primary malignancies in chronic lymphocytic leukaemia: Skin, solid organ, haematological and Richter's syndrome

Shen

Coyle

Kerridge

et al. 2021

eJHaem

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“… 34 Most RS patients are elderly, have a poor performance status and suffer from several comorbidities which limit the use of intensive chemoimmunotherapy. 40 Since the majority of patients are primary refractory to first-line treatment and only a few are able to undergo allogenic stem cell transplantation procedures, the reported estimated survival after a diagnosis of RS is usually less than one year, even with the introduction of targeted-therapy 41 , 42 and immune checkpoint inhibitors. 43 For these reasons, the standard of care of patients with RS remains a primary unmet need.…”

Section: Discussionmentioning

confidence: 99%

The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation

et al. 2021

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Complex karyotype (CK) at chronic lymphocytic leukemia (CLL) diagnosis is a negative biomarker of adverse outcome. Since the impact of CK and its subtypes, namely type-2 CK (CK with major structural abnormalities) or high-CK (CK with C5 chromosome abnormalities), on the risk of developing Richter syndrome (RS) is unknown, we carried out a multicenter reallife retrospective study to test its prognostic impact. Among 540 CLL patients, 107 harbored a CK at CLL diagnosis, 78 were classified as CK2 and 52 as high-CK. Twenty-eight patients developed RS during a median follow-up of 6.7 years. At the time of CLL diagnosis, CK2 and high-CK were more common and predicted the highest risk of RS transformation, together with advanced Binet stage, unmutated (U)-IGHV, 11q-, TP53 abnormalities. We integrated these variables into a hierarchical model: high-CK and/or CK2 patients showed a 10-year time to RS (TTRS) of 31%; U-IGHV/11q-/TP53 abnormalities/Binet stage B-C patients had a 10-year TTRS of 12%; while mutated (M)-IGHV without CK and TP53 disruption a 10-year TTRS of 3% (p<0.0001). We herein demonstrated that CK landscape at CLL diagnosis allows to refine the risk of RS transformation and we recapitulated clinico-biological variables into a prognostic model.

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“…When combined with chemoimmunotherapy (R-EPOCH) in 27 patients with RT, venetoclax showed a 48% CR, a 11% PR, and a median PFS and OS of 16.3 months both [89] (Table 3). Therefore, considering the better outcome of novel agents combined with chemo-immunotherapy, a recent review suggested a synergistic effect of these approaches [90].…”

Section: Novel Cll Therapies For Rtmentioning

confidence: 99%

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents

Tadmor

Levy

2021

Cancers

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Richter transformation (RT) is a poorly understood complication of chronic lymphocytic leukemia (CLL) with a dismal prognosis. It is associated with a switch in histopathology and biology, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or less frequently to Hodgkin’s variant of Richter transformation (HVRT). It occurs in 2–10% of CLL patients, with an incidence rate of 0.5–1% per year, and may develop in treatment-naïve patients, although it is more common following therapy. In recent years, there has been a deeper understanding of the molecular pathogenesis of RT that involves the inactivation of the TP53 tumor suppressor gene in 50–60% of cases and the activation of aberrations of NOTCH1 and MYC pathways in about 30% of cases. Compared to the preceding CLL, 80% of cases with DLBCL-RT and 30% of HVRT harbor the same IGHV-D-J rearrangements, indicating a clonal evolution of the disease, while the remaining cases represent de novo lymphomas that are clonally unrelated. Despite advances in understanding the molecular variations and the pathogenesis of the disease, there is still no significant improvement in patient outcomes. However, if no clinical trials were designed for patients with RT in the past, now there many studies for these patients that incorporate new drugs and novel combinations that are being explored. In this review, we summarize the new information accumulated on RT with special emphasis on results involving the novel therapy tested for this entity, which represents an unmet clinical need.

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Richter Syndrome

Cited by 23 publications

References 70 publications

Second primary malignancies in chronic lymphocytic leukaemia: Skin, solid organ, haematological and Richter's syndrome

Second primary malignancies in chronic lymphocytic leukaemia: Skin, solid organ, haematological and Richter's syndrome

The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents

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