Clinicopathological and laboratory parameters of plasma cell leukemia among Indian population.

Am J Blood Res 2022;12(6):190-195 www.AJBlood.us /ISSN:2160-1992/AJBR0145689 Original Article Clinicopathological and laboratory parameters of plasma cell leukemia among Indian population Harshita Dubey*, Harsh Goel*, Saransh Verma, Swati Gupta, Khushi Tanwar, Ekta Rahul, Gautam Kapoor, Jayashimman Vasantharaman, Amar Ranjan, Pranay Tanwar, Anita Chopra Laboratory Oncology Unit, Dr. B.R.A.-Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India. *Equal contributors. Received August 2, 2022; Accepted November 29, 2022; Epub December 15, 2022; Published December 30, 2022 Abstract: Background: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm distinguished by extensive clonal expansion of plasma cells in the bone marrow (BM) and peripheral blood (PB). PCL is divided into two subtypes: primary (pPCL) originates de novo without preceding multiple myeloma, while secondary (sPCL) comprises a leukemic modification that occurs as a late manifestation from previous multiple myeloma (MM). pPCL and sPCL are clinically and biologically two different entities. The molecular mechanisms of the development of PCL, either primary or secondary, remain poorly understood. We aim to present 5 years of data on clinical profiles and treatment outcomes of pPCL and sPCL patients treated at our cancer hospital in India and to find a predictive parameter of the development of PCL in cases of MM. Methods: In this study, we retrospectively reviewed and evaluated the clinicopathological features, laboratory parameters, immunophenotypic profile, and patient outcomes of 17 PCL cases diagnosed among 180 plasma cell dyscrasia patients during the study period to establish a correlation between pPCL & sPCL for diagnosis and management of PCL. Results: A total of 17 PCL patients were diagnosed among 180 plasma cell dyscrasia patients during the study period. Among PCL patients, 9 cases had pPCL (52.94% of all PCL patients), and 8 cases had sPCL (47.06% of all PCL patients). Peculiar differences were seen between the two PCL types. Both types of PCL had a younger age at the time of diagnosis, having elevated BM plasma cell infiltration percentage, frequent anemia, thrombocytopenia, elevated beta-2-microglobulin (B2M) levels, raised LDH levels, and positive M-protein in both serum and urine. In addition, SFLC assay and Immunofixation assay showed higher κ and lower λ in pPCL compared with sPCL (P<0.05). Higher Renal insufficiency was also observed in pPCL compared to sPCL (P=0.335). The survival and response to treatment of PCL patients remain considerably poor, sPCL exhibit shorter overall survival (OS) than pPCL with (median 1.75 months vs. 7 months respectively, P=0.1682). Plasma cell leukemia (PCL) needs to be diagnosed early and requires prompt initiation of treatment before patients get complications. Conclusion: Our study characterizes the clinical and laboratory features of pPCL and sPCL and may aid physicians in prognosticating the course of disease of their patients. However, future multicentre studies are the need of the hour to develop accurate diagnostic criteria and establish the efficacy of therapeutic regimens. Keywords: Plasma cell leukemia (PCL), leukemia, multiple myeloma Introduction Plasma cell leukemia (PCL) is a rare hematological malignancy distinguished by an extensive clonal expansion of plasma cells (PCs) in the bone marrow and peripheral blood, accounting for 2-4% of all multiple myeloma cases according to the 2017 WHO classification [1-3]. PCL is distinguished by the presence of ≥20% of circulating plasma cells and an absolute count of ≥2×109/L clonal plasma cells in peripheral blood [4, 5]. Circulating plasma cells per- sist in the peripheral blood despite the absence of the bone marrow microenvironment as a set of molecular abnormalities and signaling through chemokine receptors facilitates tumor development by inhibiting apoptosis of tumor cells and aiding in immune escape [6]. PCL is classified as primary (pPCL) when it develops de novo in patients without prior manifestations of multiple myeloma and accounts for 60-70% of PCL cases, while secondary PCL (sPCL) evolves in patients with pre-existing multiple myeloma and is responsible for 30-40% of Clinical and laboratory parameters of PCL PCL cases [7]. pPCL and sPCL are clinically and biologically two distinct clinical entities. However, the biological mechanisms and the responsible molecular events implicated in developing the two forms of PCL remain to be elucidated [7-11]. Since sPCL is a leukemic evolution of MM, there are no significant differences in the clinical profiles of MM and sPCL. On contrary, the clinical presentation of pPCL is more aggressive than that of observed in MM, with distinct cytogenetic aberrations, different molecular phenotype and bone marrow (BM) microenvironmental characteristics, elevated plasma cell proliferation, and clinical features such as impaired renal function, higher prevalence of lymphadenopathy, thrombocytopenias, leukocytosis, hypercalcemia, extramedullary plasmacytomas hepatosplenomegaly, pleural effusion, extramedullary plasmacytomas, more pronounced anemias, raised lactate dehydrogenase (LDH) and beta-2-microglobulin (B2M) levels [15]. It exhibits an aggressive clinical course with an unsatisfactory response to traditional therapy and has a dismal overall survival (OS) due to the destruction of red blood cells, influences extramedullary organs, and bone marrow failure [12-14]. The 5-year survival rate of PCL does not exceed 10%. In response to treatment, the prognosis of PCL has been reported to be very poor, with a median survival of (7-13 months) for pPCL, and (2-7 months) for sPCL [15]. Therefore early, accurate diagnosis is essential for the appropriate management of PCL, so that one can offer a combination of chemotherapy and autologous hematopoietic stem cell transplant (HSCT) followed by multidrug maintenance treatment employing novel agents which may prolong survival. Because of the rarity of the disease, PCL has not been thoroughly investigated in an Indian population. Therefore our present study aims to evaluate the clinicopathological features, laboratory parameters, immunophenotypic profile, and patient outcomes of all the cases of plasma cell leukemia. Material and methods Patients The study was commenced after obtaining relevant ethical clearances from our Institute Ethical Committee. Approximately 160-180 new plasma cell dyscrasia cases at our institution are diagnosed yearly. Out of these, 17 PCL cases were included based on the presence of 191 both >20% clonal plasma cells in PB and a circulating plasma cell count higher than 2×109/L. The rest of the patients with plasma cell dyscrasia (multiple myeloma, light chain disease, etc.) were excluded from the study. Methodology We retrospectively reviewed and analyzed all 17 cases of PCL from 2016 to 2021. We explored the case files from medical re (...truncated)