Circulating Plasma Cells By Routine Complete Blood Count Identify Patients With Similar Outcome As Plasma Cell Leukemia
Authors: Shah Rupin A , Mohite Satyajit , Baladandayuthapani Veerabhadran , Thomas Sheeba K. , Weber Donna M. , Wang Michael , Alexanian Raymond , Qazilbash Muzaffar H , Popat Uday R , Champlin Richard E , Shah Nina , Bashir Qaiser , Parmar Simrit , Nieto Yago , Ahmed Sairah , Orlowski Robert Z. , Shah Jatin J. 
Published: October 2019

Abstract

Introduction
Plasma cell leukemia (PCL) is a plasma cell dyscrasia that predicts for a shortened survival. World Health Organization (WHO) criteria require the presence of ≥20% circulating plasma cells (CPC) in the peripheral blood, and an absolute plasma cell count ≥2,000/µl (microliter). These criteria for PCL were established by Noel and Kyle in 1974, but subsequent studies to further validate this cut off are lacking. Since the presence of any plasma cells in the peripheral blood is now known to be a poor-risk feature, we sought to compare the overall survival of patients (pts) with any CPC observed on routine complete blood count (CBC) and differential with those that meet the WHO criteria of PCL.

Methods
We evaluated pts that received hyper-CVAD (cyclophosphamide /vincristine/doxorubicin/dex); CBAD (cyclophosphamide/bortezomib/doxorubicin/ dex), and DT-PACE (dexamethasone/thalidomide/ cisplatin /etoposide / doxorubicin/ cyclophosphamide) chemotherapy at The University of Texas M. D. Anderson Cancer Center for multiple myeloma from 2003-2012. We included pts with circulating blasts, plasma cells, or plasmacytoid cells regardless of the percentage (%) and absolute count. Pts were excluded if blasts or plasma cells were seen transiently in the setting of leukopheresis, growth factor support, or during severe sepsis. Overall survival (OS) was defined from the first detection of CPC until death due to any cause. We treated the % of plasma cells in the CBC as a continuous variable in the range from 1% to 20%. Pts with plasma cells below the cut off were defined as the “low” group and their survival was compared to the pts with plasma cells above the cut off that was defined as the “high” group. We conducted a log rank test for difference in survival curves between the two groups for each cut off, and the results were verified with a Cox model and both results were identical.

Results
85 pts were identified with presence of any CPC or PCL diagnosed based on WHO criteria; 19 had primary PCL (pPCL) and 66 pts had secondary PCL (sPCL). At the time of diagnosis, 83 (2 with unknown values) pts had a median CPC of 4% and median absolute plasma cells of 178/µL. 73 pts had cytogenetic abnormalities by florescence in situ hybridization studies, including deletion/monosomy 13 in 32 pts, IgH gene rearrangement in 24 pts and TP53 deletions in 12 pts. 17/19 pts with pPCL received bortezomib based therapy and 14/19 underwent stem cell transplant.
26 pts met the WHO criteria of PCL at some point during their disease, including 11 who met criteria when plasma cells were first detected, and 15 who had CPC < 20% initially, but subsequently met WHO criteria. Of the remaining 57 pts that did not meet the WHO criteria for presence of both absolute plasma cell count and % plasma cells, 13 met one of the criteria during the course of their disease. 44 pts had CPC but did not meet either of the WHO criteria.
Survival data were available for 79/85 pts. Pts with pPCL (either by CPC or met at least one of the WHO criteria) had a median OS of 18.5 months. pPCL pts who only had CPC and did not meet either of the WHO criteria (n=5) had a median OS of 19 months; pPCL patients who met either or both of the WHO criteria (n=13) had a median OS of 18 months. Pts with sPCL (either by CPC or met at least one of the WHO criteria) had a median OS of 5 months (n=61). sPCL pts who only had CPC and did not meet either of the WHO criteria (n=39) had a median OS of 5 months; sPCL patients who met either or both of the WHO criteria (n=22) had a median OS of 4 months.
Based on evaluating plasma cell % as a dichotomous factor with cut-off ranging from 1% to 20%, there was no significant difference in overall survival based on specific levels of plasma cell percent, and verified with a Cox model, however with many cut-offs, the sample size was small potentially limiting analysis.

Conclusion
In our analysis of OS of pts having plasma cells in their peripheral blood, we did not find any statistically significant difference based on their degree of % plasma cells or absolute plasma cells at the time of diagnosis. This supports the hypothesis that, irrespective of quantity, the presence of any plasma cells in the CBC is a poor prognostic indicator, with a similar natural history and a uniformly poor OS. While these findings will need to be validated in a larger, independent dataset, we would propose that these initial data support redefining the diagnostic criteria of PCL to include any pt with CPC observed in a routine CBC.

Disclosures:
No relevant conflicts of interest to declare.