Page 251 - Haematologica March 2020

Chronic Lymphocytic Leukemia
Clinical characteristics and outcomes of Richter transformation: experience of 204 patients from a single center
Ferrata Storti Foundation
Haematologica 2020 Volume 105(3):765-773
Yucai Wang,1 Marcella A. Tschautscher,1 Kari G. Rabe,2 Timothy G. Call,1 Jose F. Leis,3 Saad S. Kenderian,1 Neil E. Kay,1 Eli Muchtar,1
Daniel L. Van Dyke,4 Amber B. Koehler,1 Susan M. Schwager,1
Susan L. Slager,2 Sameer A. Parikh1 and Wei Ding1
1Division of Hematology, Mayo Clinic, Rochester, MN; 2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; 3Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ and 4Division of Laboratory Genetics and Genomics, Mayo Clinic, Rochester, MN, USA
ABSTRACT
The natural history, prognostication and optimal treatment of Richter transformation developed from chronic lymphocytic leukemia (CLL) are not well defined. We report the clinical characteristics and out- comes of a large series of biopsy-confirmed Richter transformation (diffuse large B-cell lymphoma or high grade B-cell lymphoma, n=204) cases diag- nosed from 1993 to 2018. After a median follow up of 67.0 months, the median overall survival (OS) was 12.0 months. Patients who received no prior treatment for CLL had significantly better OS (median 46.3 vs. 7.8 months; P<0.001). Patients with elevated lactate dehydrogenase (median 6.2 vs. 39.9 months; P<0.0001) or TP53 disruption (median 8.3 vs. 12.8 months; P=0.046) had worse OS than those without. Immunoglobulin heavy chain variable region gene mutation, cell of origin, Myc/Bcl-2 double expression and MYC/BCL2/BCL6 double-/triple-hit status were not associ- ated with OS. In multivariable Cox regression, elevated lactate dehydroge- nase [Hazard ratio (HR) 2.3, 95% Confidence Interval (CI): 1.3-4.1; P=0.01], prior CLL treatment (HR 2.0, 95%CI: 1.2-3.5; P=0.01), and older age (HR 1.03, 95%CI: 1.01-1.05; P=0.01) were associated with worse OS. Twenty- four (12%) patients underwent stem cell transplant (20 autologous and 4 allogeneic), and had a median post-transplant survival of 55.4 months. In conclusion, the overall outcome of Richter transformation is poor. Richter transformation developed in patients with untreated CLL has significantly better survival. Stem cell transplant may benefit select patients.
Introduction
Richter transformation (RT) refers to the transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma. It was first described by Dr. Maurice Richter in 1928 with a rapidly fatal case of “reticular cell sarcoma of lymph nodes” arising in the background of “lymphatic leukemia”.1 RT presents with diffuse large B-cell lymphoma (DLBCL) in over 90% of the cases, and classical Hodgkin lymphoma in 5% or less. The incidence of DLBCL type of RT is approximately 0.5-1% per year in newly diagnosed CLL patients,2 and the overall prevalence of RT is about 2-10% in CLL patients according to multiple published studies.3-5 The reported risk factors associated with RT include: advanced stage, large lymph nodes (> 3 cm), unmutated immunoglobulin heavy chain variable region gene (IGHV), del(17p), TP53 mutation, NOTCH1 mutation, and stereotyped B-cell receptor (BCR).2,6-11
Clinically, RT often presents aggressively with rapidly enlarging lymphadenopathy, prominent constitutional symptoms (fevers, night sweats, and unintentional weight loss), elevated LDH, and frequent extranodal tissue involvement.3 Treatment of RT has been challenging. The standard R-CHOP regimen used for treatment of de novo DLBCL has limited efficacy in DLBCL-type RT.12 Higher intensity chemotherapy does not improve outcomes.13-18 Stem cell transplant (SCT) has been studied in RT and
Correspondence:
WEI DING
ding.wei@mayo.edu
Received: April 8, 2019. Accepted: June 12, 2019. Pre-published: June 13 2019.
doi:10.3324/haematol.2019.224121
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/3/765
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