CLL with enlarged Abdominal Lymph Nodes (EAL) Is An Entity with Decreased Response to Fludarabine Containing Regimens.
Authors: Stadnik Elena , Salogub Galina N. , Alekseeva Yulia , Lazorko Natalija , Nikitin Eugene , Zaritskey Andrey 
Published: October 2019

Abstract
Abstract 4406
We have found only one study aimed to find prognostic significance of abdominal lymph nodes in CLL (E. Montserrat et al, 2007).
It was shown that Rai O CLL patients with enlarged abdominal lymph nodes had inferior survival. It merely means that CT scan could early reveal patients with enlarged lymph nodes. This cohort of patients is included in stage 0 only due to the fact of unavailability of CT scan at the times Rai and Binet staging were described (1975, 1977).
The aim of the study was to evaluate prognostic significance of abdominal lymph nodes enlargement for the response to FC and FCR

Patients and methods
71 untreated CLL patients were included according to the intent to treatment by fludarabine containing regimens (FC and FCR). Staging was performed according to Binet system. Stage B and C patients were included. Lymph nodes were revealed by CT and ultrasound before therapy (Lymph nodes more than 10mm in diameter were considered as abnormal and more than 100 mm in diameter were considered as bulky). CD38 was performed by CytoFlow (cut off 30%). Mutation analysis was done with PCR and sequencing (E.Nikitin, Hematological centre, Moscow), (cut off 98%).
CR was defined according to NCI criteria.
The patients were treated and followed-up by the single team of physicians, there were no losses of follow-us.
SPSS - 17 statistical program was used for analysis.

Results
Overall response (OR) was 86% (61 pts), the rate of CR was 55% (39 pts), the rate of PR 31% (22 pts). In the whole group, FC: OR 81%, CR 46%, PR 35%. FCR: OR 91%, CR 67%, PR 24%), median of PFS was 26 mons (21 mons for FC and 35 for FCR, p=0.006). CD38 positivity, unmutated type and stage C had adverse prognostic significance in the whole group (p= 0,04; p=0,05; p=0,02), in FCR subgroups, mutation status and CD38 had marginal significance in FCR(p=0.9, p=0.75).
Abdominal lymph nodes were enlarged in 41 pts (58%), 16 pts had bulky EAL(23%). PFS was lower in the group of patients with EAL in comparison to patients without EAL(18 and 48 mons, p 0.001). Difference in PFS has been also revealed in FC and FCR subgroups: 16 and 25 mons, p=0,003 for FC; 22 and 56 mons, p=0,01 for FCR (Fig.1)
All fludarabine containing regimens resistant patients appeared to have EAL (10 pts). The duration of CR and PR were longer in patients without EAL(resp.p = 0.03 and 0.06, Fig. 2).
The differences of PFS were also studied inside the groups defined by standard prognostic markers.
CD38-, EAL+ patients had median PFS of 23mons, CD38-, EAL- patients-median not achieved (p= 0.01)
CD 38+EAL+patients had median PFS of 12 mons, CD38+EAL- patients – 30 mons (p=0,04)
Thus, CD38+ patients without EAL had even better PFS than CD38- patients with EAL.
VH-mut+ EAL+ patients had median PFS of 18 mons, VH-mut+ EAL- patients – 58 mons (p=0,06)
VH-mut- EAL+ patients had median PFS of 11 mons, VH-mut- EAL- patients – 18 mons (p=0,06)
Thus, unmutated patients wit EAL had similar PFS with mutated patients without EAL.
Stage B EAL+ patients had median PFS of 20 mons, Stage B EAL- patients – 58 mons (p=0,004)
Stage C EAL+ patients had median PFS of 15 mons, Stage C EAL- patients – 21 mons (p=0,05)
Thus, patients with stage B without EAL had PFS four times better, than patients with stage C, EAL+.
Median PFS is similar in patients stage B EAL+ and stage C EAL-.
The response equal to PR and more than PR after three cycles of chemotherapy was more frequent in patients without EAL (65% vs 18%, p < 0,001)

Conclusion
Enlarged abdominal lymph nodes(EAL) is an adverse prognostic marker for response both to FC and FCR. Differences in PFS according to EAL were also revealed inside standard prognostics subgroups (mutation status and CD38,stage).
Even more, PFS of patients with standard adverse prognostic factors without EAL were similar to patients without standard adverse prognostic with EAL.
CLL with EAL is a separate entity of CLL.

Disclosures:
No relevant conflicts of interest to declare.