BCL-2 and c-MYC Rearrangements in Leukemic Phase of Diffuse Large B Cell Lymphoma Predicts Central Nervous System Involvement

Introduction

Diffuse large B-cell lymphomas (DLBCL) are the most common lymphoid neoplasms but rarely with leukemic phase. Few studies had described the clinical characteristics of DLBCL with leukemic phase and found that these patients had high incidence of centre nervous system (CNS) involvement but with no knowledge of the reason.

Methods

We reviewed the clinical characteristics of 40 DLBCL patients in leukemic phase during 2001 and 2012. The DNA probes were LSI BCL2 and MYC Dual Color, Break Apart Rearrangement Probe were usedto detect the abnormalities of 18q21 and 8q24 by FISH.We also used LSI IGH/BCL2 Dual Color, Dual Fusion Translocation Probe and LSI IGH/MYC/CEP 8 Tri-Color Dual Fusion Probesto detect the partner fusion genes of BCL2 or MYC.

Results

The median age of these 40 patients was 46 years(range, 15-75) with 19 men patients. The median WBC was 12.32×10⁹/l(range, 1.2-66.57)with a median 35.74% (range, 1–90) of circulating lymphomatous cells identified by flow cytometry.14 of these 40 patients (35%)had CNS involvement.There were gender differences between CNS involvement or not. Ten of the fourteen patients (71.4%) with CNS involvement were male, while in non CNS involvement group only 9 of 26 (34.6%) cases were male (p=0.046).57.1% patients with CNS involvement had IPI scores 4-5, which was higher than those without CNS involvement (11.5%, p=0.001).All of these 14 patients had elevated LDH was and was significantly higher than those without (61.5%, p=0.007).

There were 14 patients (33.5%) had the BCL2 or MYC aberrationrespectively and nine of them simultaneously had both of c-MYC and BCL2 rearrangement, which we defined as double-hit DLBCL patients here. No IGH/BCL2 fusion gene was detected and only one patient with IGH/MYC fusion with c-MYC rearrangement. Eight of the nine double-hit patients had CNS involvement, while only six of the other 31 patients with either BCL2 or MYC or none rearrangements had CNS involvement (88.9% vs. 19.4%; p＜0.001). By logistic regression analysis, we found that double-hit with BCL2 and c-MYC rearrangement was the only one independent factor correlated with CNS involvement with relative risk 15.3 (95% confidence interval, 1.4-171.1).

Conclusion

DLBCL patients in leukemic phase had higher incidence of CNS involvement and double-hit with BCL2 and c-MYC gene rearrangements might contribute to CNS involvement in this population.