Distinct Clinico-Pathological Profile of Plasma Cell Leukemia Patients from North India

Abstract Introduction: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm where clonal plasma cells comprise ≥ 20% of peripheral blood (PB) leukocytes and/or absolute clonal PB plasma cell count is ≥ 2×109/L. Primary plasma cell leukemia (PPCL) originates de novo, whereas, secondary plasma cell leukemia (SPCL) evolves from pre-existing multiple myeloma (MM). Literature does reveal a few large case series on PCL, however, data on this rare neoplasm is very sparse from Indian sub-continent. We present clinico-pathological profile 14 cases of PCL from single tertiary care centre of north-India. Materials and methods: Archival files were screened for period of 8 years (Jan 2007 to Dec 2014) and clinico-pathological profile, including overall survival, of patients of PCL was systematically analysed, retrospectively. Results: Ten PPCL and four SPCL patients were traced in duration of 8 years, all belonging to north-Indian states of Punjab and Haryana. Eight PPCL and three SPCL patients had complete clinical data. Our patients had less frequent renal failure (12.5%), more frequent hepatomegaly (75%) and non-secretory type (33%) disease. Flow cytometric immunophenotyping revealed expression of CD138 (67%), CD56 (33%) and CD20 (0%), which was different from reported western data. With novel therapeutic agents, these patients fared a higher median survival of 15 months. Conclusion: Our patients of PCL from neighbouring states of north-India have a distinct clinico-pathological profile, with better survival as compared to existing literature. The significance of our findings must be tested in a larger patient cohort and must be supported with molecular and cytogenetic investigations to unmask any significant pathogenesis. Disclosures No relevant conflicts of interest to declare.

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Clinico-Pathological Spectrum of Primary Plasma Cell Leukemia Diagnosed at a Tertiary Care Centre in South India Over 5 Year Period

Indian Journal of Hematology and Blood Transfusion ◽

10.1007/s12288-011-0133-8 ◽

2012 ◽

Vol 28 (3) ◽

pp. 170-174 ◽

Cited By ~ 3

Author(s):

Rakhee Kar ◽

Sarah Grace Priyadarshini ◽

M. Niraimathi ◽

Debdatta Basu ◽

Bhawana Ashok Badhe

Keyword(s):

Plasma Cell ◽

South India ◽

Tertiary Care ◽

Plasma Cell Leukemia ◽

Care Centre ◽

Cell Leukemia ◽

Tertiary Care Centre ◽

Primary Plasma Cell Leukemia

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Plasma cell leukemia in North India: retrospective analysis of a distinct clinicohematological entity from a tertiary care center and review of literature

Blood Research ◽

10.5045/br.2016.51.1.23 ◽

2016 ◽

Vol 51 (1) ◽

pp. 23 ◽

Cited By ~ 1

Author(s):

Karthik Bommannan ◽

Man Updesh Singh Sachdeva ◽

Pankaj Malhotra ◽

Narender Kumar ◽

Prashant Sharma ◽

...

Keyword(s):

Retrospective Analysis ◽

Plasma Cell ◽

Care Center ◽

Tertiary Care ◽

Plasma Cell Leukemia ◽

North India ◽

Tertiary Care Center ◽

Review Of Literature ◽

Cell Leukemia

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Plasma Cells from Secondary Plasma Cell Leukemia Display Different Cytogenetics Pattern When Compared with Primary Plasma Cell Leukemia.

Blood ◽

10.1182/blood.v106.11.3267.3267 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3267-3267

Author(s):

Natalia C. Gonzalez-Paz ◽

Scott Van Wier ◽

Rafael Santana-Davila ◽

Gregory Ahmann ◽

Tammy Price-Troska ◽

...

Keyword(s):

Plasma Cell ◽

De Novo ◽

Plasma Cell Leukemia ◽

Cell Leukemia ◽

Ras Gene ◽

Disease Evolution ◽

Cytogenetic Abnormalities ◽

Ras Mutations ◽

Specific Pcr ◽

Secondary Plasma

Abstract Background: Plasma cell leukemia (PCL) is a rare plasma cell (PC) dyscrasia which may be designated as primary (PPCL) or de novo PCL when recognized at the time of diagnosis and secondary (SPCL) when there is leukemic transformation of a previously recognized multiple myeloma (MM). PCL has been reported to exhibit distinct clinical and immunophenotypic features that distinguish it from MM, but little is known about the specific genetics of this disease. To better understand the genetic features of the clonal PC from PPCL and SCPL we assessed in these patients the molecular and cytogenetic abnormalities most commonly found in MM. Patients and Methods: In our study we analyzed 3 groups of patients; 18 with PPCL, 23 with SPCL and a control group of 345 newly diagnosed MM previously published. Diagnostic criteria for PCL followed the presence of >2 x103/L PC in PB (Kyle et al. Arch Intern Med1974; 133–813–8). Cytogenetic abnormalities were assessed by the c-Ig FISH method; mutational analysis was performed using Conformational-sensitive gel electrophoresis (CSGE). Methylation was analyzed by methyl specific PCR (MSP) after bisulfite genomic DNA modification. Results: Translocation of immunoglobulin heavy chain with Cyclin D1 (t (11; 14)) was present in 76.9% (10 of 13) of PPCL, 71% (5 of 7) of SPCL, in contrast to 15.8% (53 of 336) of MM cases. Translocations’ involving the FGFR3-MMSET genes (4p16.3 locus) and c-MAF (16q32) genes were not observed among 10 patients studied with PPCL, but were present in 12.7 % each in SPCL. The t (4;14)(p16;q32) was present in 12.7% cases of MM and the t(14;16)(q32;q23) was present in 4.6 % of MM cases. Deletion of 17p13.1 (p53 locus) was found in 10% (37 of 345) of MM cases, 53.8% (7 of 13) for PPCL and 42.8% (3 of 7) for SPCL. Deletion of 13q was present in 54.2% (176 of 325) of MM, 76.9 % (10 of 13) of PPCL and 57.1% of SPCL. Ras mutations were found in 15% (2/13) of PPCL, located in codon 1 and 2 of the K-ras gene. In addition, 23% for SPCL presented mutations in the N-ras gene. Two mutations were located in codon 2 of N-ras and 1 patients in showed a mutation in codon 1 of K-ras gene. Ras mutations were present in 27% of MM cases. Mutations for p53 gene were present in 30.7% (4/13) of PPCL, 17% (3/17) for SPCL and 5% for MM. Methylation specific PCR for p16 gene was found in 23% (3/13) of PPCL, 29% of SPCL and 33.9% (149/439) of MM. Hypermethylation of p14 was not detected in PPCL but a 23 % was found in SPCL. Conclusions: In this study we demonstrate that PCs from PPCL more frequently carry the t (11; 14). Comparing SPCL and MM, PC’s from de novo PPCL do not show t (4; 14) or (16; 14). Deletion of 13q was more prevalent among patients with PPCL. Ras mutations appear to be as frequent in MM as in PPCL and SPCL. Mutations in p53 appeared to be more prevalent in PPCL than in SPCL and MM. Hypermethylation of p16 does not differ while hypermethylation of p14 is more frequent in SPCL than PPCL. These characteristics may lead to a different onset or disease evolution of PPCL compared to MM and secondary plasma cell leukemia and this may be important for diagnostic and treatment.

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Plasma Cell Leukemia: Case Series From a Tertiary Center with Review of Literature

Indian Journal of Hematology and Blood Transfusion ◽

10.1007/s12288-011-0097-8 ◽

2011 ◽

Vol 28 (1) ◽

pp. 10-14 ◽

Cited By ~ 8

Author(s):

Shano Naseem ◽

Sukhpreet Kaur ◽

Ritu Gupta ◽

Rajesh Kashyap ◽

Soniya Nityanand

Keyword(s):

Plasma Cell ◽

Case Series ◽

Plasma Cell Leukemia ◽

Review Of Literature ◽

Cell Leukemia ◽

Tertiary Center

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Primary Plasma Cell Leukemia: Results of a Retrospective Italian Multicentric Survey.

Blood ◽

10.1182/blood.v114.22.2885.2885 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2885-2885

Author(s):

Livio Pagano ◽

Caterina Giovanna Valentini ◽

Valerio De Stefano ◽

Adriano Venditti ◽

Giuseppe Visani ◽

...

Keyword(s):

Plasma Cell ◽

Response Rate ◽

Conflicts Of Interest ◽

Alkylating Agents ◽

Plasma Cell Leukemia ◽

High Dose ◽

Cell Leukemia ◽

Front Line ◽

Line Therapy ◽

Primary Plasma Cell Leukemia

Abstract Abstract 2885 Poster Board II-861 Background: Epidemiological and clinical information on Primary Plasma Cell Leukemia (pPCL) are rarely reported. Aims: To evaluate in patients (pts) with pPCL the clinical features, the prognostic factors, and the efficacy of treatments. Patients and Methods: A multicenter retrospective cohort study was carried out between January 2000 and December 2008 in 26 Italian hematology divisions. A total of 128 cases of PCL were collected, and 73 of them (57%) were classified as primary (M/F 43/30). Results: The median age was 63 years (range 32-86). At diagnosis the median values of peripheral blood plasma cells and bone marrow plasma cell infiltration were 2.7 × 10 9/L (range 0.4-49.9) and 80% (range 37-100), respectively. The median values of hemoglobin, white blood cell count, and platelet counts were 9.1 g/dl (range 4.8-12.9), 13.7 × 10 9/L (range 1.3-56.7), 116 × 10 9/L (range 8-428), respectively. Extramedullary disease was present in ten cases (14%) and included testis, muscular, neuromeningeal, and cutaneous localization. At diagnosis, 64 pts (88%) had at least one CRAB sign, namely 35 pts (48%) had low hemoglobin level, 20 pts (27%) calcium ≥11 mg/dl, 32 pts (44%) creatinine ≥2 mg/dl, and 47 pts (64%) had osteolysis. In 41 pts (56%) cytogenetic study was performed, revealing an unfavourable karyotype in 17 (23%), in 13 of them del(13q-). Seventy-two pts received front-line therapy (1 died early, receiving only support treatments and steroids), that included antracycline-containing regimens in 36 pts (50%), and single alkylating agents in 17 pts (24%, 9 cyclofosfamide and 8 melphalan). In 11 of them Bortezomib (BTZ, n= 7) or Thalidomide (THAL, n= 4) were also employed. Finally, 19 pts (26%) received BTZ (4) or THAL (5) or both (10) as unique treatment. Twenty-one pts (29%) underwent autologous stem cell transplantation (SCT) as part of front-line therapy, followed by allogeneic-SCT in four cases; two additional pts underwent only allogeneic-SCT. A complete or partial remission after front-line therapy was achieved in 20 pts (27%) and 19 pts (26%) respectively (overall response rate 53%). The median overall survival (OS) was 13.1 months (range 0.5-75.8); 30.6 months (range 4.7-75.8) in responder pts and 4.2 months in non-responder ones (range 0.5-75.6, univariable hazard ratio, HR, 0.28, 95% CI 0.11-0.39). In the responder pts the median progression free survival (PFS) was 17.2 months (range 1.4-72.1). Of note, in SCT pts the median OS and PFS were 38.1 months (range 4.8-75.8) and 25.8 months (range 1.4-72.1) respectively, with a significant advantage with respect to non-transplanted pts in OS (median 9.1 months, range 0.5-75.6, HR 0.28, 95% CI 0.16-0.52) and in PFS (median 7.3 months, range 1.7-17.7, HR 0.29, 95% CI 0.04-0.44). The low number of allo-SCTs did not allow a reliable separate statistical analysis. A multivariable Cox proportional hazard regression analysis showed that OS was influenced by lack of initial response (HR 2.62, 95% CI 1.04-6.57), albumin <3 g/dl (HR 3.33, 95% CI 1.64-6.76), and SCT (HR 0.34, 95% CI 0.12-0.98). Pts with hypercalcemia at diagnosis had a shorter PFS (HR 4.0, 95% CI 1.04-15.24); the PFS was favourably influenced by SCT (HR 0.05, 95% CI 0.009-0.28). Overall, the use of BTZ and/or THAL did not influence the OS and PFS. Conclusions: pPCL is a highly aggressive lymphoprolipherative malignancy, characterized by a poor prognosis and a low response rate to conventional therapy. The use of high-dose chemotherapy followed by autologous or allogeneic-SCT is a very effective therapy leading to 66% increase in the OS and to 95% increase in PFS in respect to non-transplanted pts. Apparently, the use of novel drugs such as BTZ and THAL did not produce a further amelioration in the patient outcome. However, those latter findings should be taken with caution, given the relatively low number of treated pts. Disclosures: No relevant conflicts of interest to declare.

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Biclonal Multiple Myeloma- A Case Series

10.21203/rs.3.rs-739216/v1 ◽

2021 ◽

Author(s):

Somnath Roy ◽

Satvik Khaddar ◽

Amit Agrawal ◽

Geeta Rathnakumar ◽

Lingaraj Nayak ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Tertiary Care ◽

Case Series ◽

Standard Chemotherapy ◽

Tertiary Care Centre ◽

Single Clone ◽

Immunofixation Electrophoresis ◽

Plasma Cell Dyscrasias ◽

Biclonal Gammopathy

Abstract Multiple myeloma is a prototype of plasma cell dyscrasias characterized by monoclonal abnormal proliferation of immunoglobulin secreting plasma cell in the bone marrow ; resulting in production of monoclonal (M) protein (IgG,IgA,IgM,IgD) and or light chain concentrations (kappa or lamda) identified by protein electrophoresis and or immunofixation of serum or urine. The term biclonal multiple myeloma are defined by coexistence of two different M components, which could be either from a single clone or two separate clones producing two distinct bands in electrophoresis and or immunofixation of serum or urine. Biclonal gammopathy is a rare entity with upto 1% of newly diagnosed case of multiple myeloma have two M component in serum immunofixation electrophoresis. Here we share our experience of four cases of biclonal myeloma successfully diagnosed and treated with standard chemotherapy with satisfactory clinical outcome from a single tertiary care centre.

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Genome-Wide Analysis of Primary Plasma-Cell Leukemia Identifies Recurrent Imbalances Associated with Transcriptional Profile Alterations

Blood ◽

10.1182/blood.v118.21.2878.2878 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2878-2878

Author(s):

Laura Mosca ◽

Pellegrino Musto ◽

Katia Todoerti ◽

Marta Lionetti ◽

Luca Agnelli ◽

...

Keyword(s):

Plasma Cell ◽

Mutational Analysis ◽

Conflicts Of Interest ◽

Gene Dosage ◽

Snp Array ◽

Plasma Cell Leukemia ◽

Cell Leukemia ◽

Open Label ◽

Genome Wide ◽

Primary Plasma Cell Leukemia

Abstract Abstract 2878 Primary plasma-cell leukemia (pPCL) is an aggressive, rare variant of plasma cell (PC) dyscrasia characterized by extra-medullary proliferation of PCs, high genomic instability and very poor prognosis. The present study was aimed at investigating global genomics in 17 pPCL recruited in an open-label, exploratory, single-arm, two-stage study from the GIMEMA myeloma network designed to evaluate the safety and antitumor activity of lenalidomide in combination with low dose dexamethasone as first-line therapy in pPCL. All the samples were characterized for the main chromosomal aberrations by Fluorescence In-Situ Hybridization (FISH). Specifically, 13q and 17p deletions have been identified in 13 (76.5%) and 6 (35.3%) cases, respectively; the presence of t(11;14) translocation was found in 7 patients (41.2%), t(4;14) in 2 (11.8%) and t(14;16) in 7 (41.2%). To better define the chromosomal alterations of this set of patients, we further investigated them by means of Human Mapping 250K Nsp SNP-array (Affymetrix). SNP-array data were fully concordant with FISH results as regards 13q and 17p deletions in the analyzed patients. Among the copy number alterations identified by mapping analysis the most frequently gained chromosomal region was represented by 1q (9 cases, 52.9%); 1p, 8p, 14q, and 16q arms were affected by loss of DNA material in more than 40% of cases. Moreover, four patients showed gain at 7q (23.5%), one case displayed a near tetraploid karyotype and another one had a hyperdiploid-like pattern. Most of the minimally altered regions identified on the different chromosomes encompassed genes that have been reported to be deregulated in PC dyscrasia, such as CDKN2C (mapped to 1p32.3), FAM46C (1p12), CKS1B (1q21.2), PARK2 (6q26), PPP2R2A (8p21.2), RB1 and MIR-15A/16-1 (13q14.2), TRAF3 (14q32.32), CYLD (16q12.1), WWOX (16q23.3-q24.1), and TP53 (17p13.1). The mutational analysis of the most frequently mutated exons (5–9) of TP53 gene revealed the presence of coding mutations in 4 patients (23.5%), three of which carried a monoallelic deletion including the gene locus. This supports the knowledge that the prevalence of TP53 mutations increases in more advanced disease and is strongly associated with hemizygosity. Genome-wide profiling data were then integrated with the transcriptional profiles generated on Gene 1.0 ST array (Affymetrix). Our analysis (Wilcoxon rank-sum test at a P <0.001) identified 134 transcripts whose expression levels strongly correlated with the occurrence of allelic imbalances, all of them in the previously described altered regions; specifically, 42 mapped to gained regions on 1q (40/134=29.9%) and 7q (1.5%), and 92 mapped to deleted regions on 1p (10.4%), 6q (6.7%), 8p (10.4%), 13q (9.7%), 14q (18.7%), 16q (6.0%) and 17p (6.7%). Enriched categories in functional annotation analysis are protein metabolism, transport, catabolic processes as the proteasome ubiquitination pathway (PSMC6, PSMA3, PSMB4 and PSMD4), and telomere organization and maintenance (PINX1, PARP1 and WRN). Overall, our data highlighted a wide gene-dosage effect, suggesting that genomic structural abnormalities in pPCL closely reflect in expression imbalances. Disclosures: No relevant conflicts of interest to declare.

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Plasma Cell Leukemia Presenting as a Chest Wall Mass: A Case Report

Case Reports in Oncology ◽

10.1159/000447353 ◽

2016 ◽

Vol 9 (2) ◽

pp. 338-343 ◽

Cited By ~ 1

Author(s):

Ahmed Ali ◽

Yonette Paul ◽

Stanley Madu Nwabudike ◽

Onyekachi Ogbonna ◽

Mica Grantham ◽

...

Keyword(s):

Chest Wall ◽

Plasma Cell ◽

Plasma Cells ◽

De Novo ◽

Standard Of Care ◽

Interesting Case ◽

Plasma Cell Leukemia ◽

Cell Leukemia ◽

Current Standard ◽

Aggressive Clinical Course

Plasma cell leukemia (PCL) is an uncommon neoplasm of plasma cells, with an aggressive clinical course and poor outcome, even with current standard of care. It can occur either de novo (primary PCL) or as a progression of multiple myeloma (MM). This disease has unique diagnostic criteria but certain genetic markers and clinical features may overlap with MM. Due to the low prevalence of PCL, guidelines on its management are extrapolated from the management of MM and based on small retrospective studies and cases reports/series. We present an interesting case of PCL in a middle-aged African-American male, who was diagnosed incidentally after chest wall imaging for an unrelated complaint. The diagnostic approach, management and outcomes of PCL are discussed.

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