Abstract
Background:
Primary plasma cell leukemia (PPCL) is a rare and highly aggressive form of plasma cell dyscrasia, characterized by the presence of circulating plasma cells (20% or ≥ 2 × 10⁹/L absolute) and dismal outcomes. Comprehensive data on clinicopathologic features and survival determinants in PPCL remain limited due to its low incidence. Existing literature is largely restricted to single-center case series or retrospective analyses with small patient cohorts. As a result, key determinants of survival and optimal management strategies for PPCL remain poorly defined. To address these knowledge gaps, we conducted an analysis of a pooled real-world database comprising patients with PPCL. This study aims to elucidate the clinical, laboratory, and pathological factors most strongly associated with overall survival, providing a foundation for improved prognostication and patient care.
Methods:
To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled and analyzed a pooled real-world database of cases that satisfy the diagnostic criteria for PPCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).
Results:
A total of 247 patients with confirmed PPCL were identified. The median age was 57 with slight male preponderance (M:F=1.3). The cohort median OS was 13 months, and the median time from symptoms to diagnosis was 1.25 months. Constitutional symptoms, hepatosplenomegaly (HSM), and lymphadenopathy were present in 57%, 43%, and 15%, respectively. PPCL comprised non-secretory (15%), IgG (44%), IgA (17%), IgM (3%), and light chains (21%). The majority of the monoclonal immunoglobulins were associated k-light chains (54%). Age>60, fever, bone and lymph nodes involvement, k-associated disease, platelets<100K, complex cytogenetics, and abnormalities of chromosomes 13 and 17 were associated with worse OS. Hypercalcemia and elevated LDH also correlated with worse OS. While %BM plasma cells <60, IgM and light chain disease had numerically better OS, they did not reach statistical significance. Sex, HSM, hemoglobin, b-2 microglobulin, and m-protein levels,% or absolute plasma cell values did not significantly impact OS. Platelet-WBC-Ratio (PWR) <5 was associated with worse OS (9 vs. 19 months, p=0.03). Compared to no treatment, chemotherapy, allo-SCT, and auto-SCT had increasingly better survival (0.5 vs. 10 vs. 17 vs. 24 months, p<0.0001). Furthermore, maintenance therapy was associated with better OS (14 vs. 43, p=0.03). Patients who achieved complete responses had significantly improved OS compared to those with partial or no response (33 vs. 14 vs. 2 months, p<0.0001).
Conclusions:
This pooled real-world analysis identifies key clinicopathologic determinants of survival in primary plasma cell leukemia. Furthermore, treatment modalities involving allogeneic and autologous stem cell transplantation, as well as maintenance therapy, significantly impact prognosis and the achievement of a complete response, conferring the greatest survival benefit. These findings underscore the need for early, aggressive intervention and highlight critical prognostic factors that can inform clinical decision-making and individualized patient care in PPCL.
