Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma

Abstract

We hereby report the clinical and biologic features of 33 of 4680 (0.7%) patients with chronic lymphocytic leukemia (CLL), managed at 10 Italian centers, who developed Hodgkin lymphoma (HL), a rare variant of Richter syndrome. The median age at CLL and at HL diagnosis were 61 years (range 41-80) and 70 years (range 46-82), respectively, with a median interval from CLL to the diagnosis of HL of 90 months (range 0-258). In 3 cases, CLL and HL were diagnosed simultaneously. Hl was characterized by advanced stage in 79% of cases, International Prognostic Score (IPS) ≥4 in 50%, extranodal involvement in 39%, B symptoms in 70%. Prior treatment for CLL had been received by 82% of patients and included fludarabine in 67%. Coexistence of CLL and HL was detected in the same bioptic tissue in 87% of cases. The most common administered treatment was the ABVD regimen given to 22 patients (66.6%). The complete response (CR) rate after ABVD was 68%, and was influenced by the IPS (P = .03) and interval from the last CLL treatment (P = .057). Survival from HL was also influenced by the IPS (P = .006) and time from the last CLL treatment (P = .047). The achievement of CR with ABVD was the only significant and independent factor predicting survival (P = .037). Taken together, our results show that the IPS and the interval from the prior CLL treatment influence the likelihood of achieving CR after ABVD, which is the most important factor predicting survival of patients with CLL developing HL.

Hodgkin lymphoma transformation of chronic lymphocytic leukemia—A real life data from the Polish Lymphoma Research Group

“…Whether this is a true phenomenon is unclear since it might result from the fact that in real life histopathology, verification of disease progression (lymphadenopathy with concomitant B symptoms) is rather made in patients with low than increasing lymphocyte counts. Our results are similar to the results of Mauro et al and Parikh et al (median absolute lymphocyte count of 1.7 × 10 9 ) but contrast the results of Tadmor et al, where a significant proportion of patients still had lymphocytosis at HvRS diagnosis . The biological and clinical significance of lymphopenia in advanced CLL/SLL is unknown although lymphopenia is a well‐known adverse prognostic factor in classical HL .…”

“…All analyzed patients were diagnosed with advanced stage Hodgkin lymphoma and the majority of them presented with B symptoms, and 50% had an IPS greater than or equal to 4—similar with other studies . The most prevalent subtype was nodular sclerosis (NS), unlike in other studies where mixed cellularity (MC) predominated .…”

“…Interestingly, active CLL/SLL was not predictive of response to ABVD in our group. Although we were not able to identify any factors predicting response, which might result from the small number of patients, other reports suggest that high IPS and a shorter time from the last CLL/SLL treatment were negatively associated with a likelihood of obtaining CR …”

“…Because of the low incidence of HvRS, the clinical data on this entity are still scarce. The largest description of patients with HvRS was reported in 2017 from 10 Italian centers, covered more than 21 years, and included only 33 patients . The biggest group reported so far by Bockorny of 86 patients was a pooled analysis of world literature from 1975 to 2011, which by definition is biased by way of selecting cases for publication .…”

Wnt signalling pathways in chronic lymphocytic leukaemia and B‐cell lymphomas

“…CLL patients can develop so‐called Richter syndrome (RS), which is when the disease transforms into a high‐grade lymphoma (Rossi and Gaidano, ), most commonly to DLBCL (2–7% of CLL patients in clinical trials) and HL (0.4–0.7% of CLL patients) (Mauro et al ., ). An analysis of IGHV‐D‐J genes revealed that 80% of the DLBCL‐RS are clonally related to the preceding CLL phase, while this is true for only 40–50% of HL‐RS.…”