Abstract P132

Richter transformation of CLL to Hodgkin lymphoma

Background: Richter transformation of chronic lymphocytic leukemia (CLL) to Hodgkin lymphoma (HL) is a very rare phenomenon which accounts for less than 1% of all cases of transformation of CLL to high-grade lymphomas. Particularly challenging is the question, whether we are dealing with the clonal evolution of one disease or two distinct lymphomas. The answer lies in assessment of clonality by determining the specific IgHV rearrangement of the CLL cells and then comparing it with the DNA from the isolated HRS cells in the aim of finding the identical rearrangement. The goal of the study was to assess clonality of CLL transformed to HL in our cohort of patients.

Methods: The DNA isolated from the CLL cells was obtained either from the lymph node biopsies, trephine biopsies or peripheral blood. The Hodgkin and Reed-Sternberg cells (HRS) from HL biopsies were isolated by technique of laser microdissection. The screening of clonal Ig rearrangement was performed by a PCR method according to the certified protocol Biomed-2. The protocol enables detection of IgH, IgK and IgL clonality and the methodology has a detection threshold the presence of at least 10-15% of clonal cells in a polyclonal background. In the case of detection of a clonal rearrangement, we sequenced the given rearrangement in order to determine the exact sequence composition.

Results: We identified 29 patients with Richter transformation of CLL to HL between 2008 and 2024 and data of IgH clonality rearrangement on 20 patients will be presented. At initial diagnosis of CLL patients 0 had TP53 mutation or del 17p and 4 had unmutated IgHV. Out of 29 patients 6 had mixed cellularity histology and 4 had nodular sclerosis histology. EBV positivity was proved in 1 patient. Currently, out of 13 patients with completed analysis we detected identical IgH rearrangement in two patients and thus proved clonal relation between CLL and HL. Clonality analysis is ongoing in seven patients. Quality and quantity of available DNA either from CLL or HRS cells vary significantly based on the source of histology, preservation medium, time duration since the date of diagnosis and obtaining sufficient DNA material from scarce HRS cells. Conclusion: Understanding the biology of Richter transformation to Hodgkin lymphoma is crucial to personalize the treatment and improve patient's survival.

Authors

Mária Maco, Heidi Mocikova, Markéta Kalinová, Zuzana Prouzová, Patrik Flodr, Anna Panovská, Tomáš Arpáš, Martin Šimkovič, Tomáš Kozák