Multiple myeloma patients with low proportion of circulating plasma cells had similar survival with primary plasma cell leukemia patients

2014 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Gang An ◽  
Xiaoqi Qin ◽  
Chirag Acharya ◽  
Yan Xu ◽  
Shuhui Deng ◽  
...  
Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4951-4951
Author(s):  
Pellegrino Musto ◽  
Maria Teresa Petrucci ◽  
Fortunato Morabito ◽  
Francesco Nobile ◽  
Fiorella D'Auria ◽  
...  

Abstract Abstract 4951 Background Primary Plasma Cell Leukemia (PPCL) is an aggressive, rare variant of multiple myeloma, with clinical, molecular and phenotypic peculiarities, which accounts approximately for 2% to 4% of all myeloma diagnoses. The prognosis of PPCL patients is usually poor, with less than half of patients responding to conventional chemotherapy and a median survival of 7 months. Even by using autologous or allogeneic transplant procedures, survival generally does not exceed three years. Bortezomib has recently provided some promising results in this setting, but, given all the above, new treatments for PPCL are greatly awaited. Lenalidomide is a new immunomodulating agent with great efficacy in multiple myeloma, especially when associated with dexamethasone or other drugs. There are, indeed, some sporadic case reports of PPCL patients treated with lenalidomide as salvage therapy, but no data are currently available on the use of this drug as first line therapy in this disease. Patients and Methods On March, 2009, we started an open label, prospective, multicenter, exploratory, single arm, two-stage study aiming to evaluate safety and antitumor activity of the lenalidomide/low dose dexamethasone combination (Rd), as first line therapy in patients with PPCL. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were TTP, PFS, OS, percentage of eligible PPCL patients able to collect peripheral blood stem cells and to undergo autologous or allogeneic stem cells transplantation after Rd, serious and severe adverse event rate. According to this study protocol, all eligible, newly diagnosed adult patients with PPCL receive Lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Oral dexamethasone is administered at a dose of 40 mg daily on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, patients who achieve at least PR and not eligible for autologous or allogeneic stem cell transplantation, continue with Rd until clinically appropriate (disease progression, unacceptable toxicity, patient's decision to leave the protocol). In these patients, a maintenance dose of lenalidomide alone equal to 10 mg/die days 1-21 every month is considered after at least 8 full dose Rd cycles. Patients responding after 4 Rd cycles and eligible for transplant procedures, proceed according to single Centre transplant policy. Patients not responding after 4 cycles or progressing under Rd treatment are considered off-study. Appropriate contraception methods and anti-thrombotic prophylaxis are planned. Results Four enrolled patients (1 male, 3 female, mean age 65 years, range 58-69) are currently evaluable for early response. All had unfavourable cytogenetics, including del13, t(4;14), t (14;16), or a complex karyotype. Circulating plasma cells ranged from 4.4 to 9.2 ×10e9/l. One patient had at baseline a moderate degree of renal failure (serum creatinine levels 2 mg/dl). After at least 2 Rd cycles (range 2-4), two PR and two VGPR were achieved (overall response rate 100%), with disappearance or near complete reduction of circulating plasma cells in all cases. The most relevant toxicities were grade 3 neutropenia and pneumonia, occurring in one patient and resolved by appropriate lenalidomide dose reduction, introduction of G-CSF and antibiotic therapy. One patient died in PR, due to causes unrelated to PPCL or treatment. As, according to the Simon, two-stage design adopted, more than two responses occurred within the first ten patients enrolled (stage 1), a total of 22 PPCL subjects will be accrued to complete the stage 2 of the trial. Conclusions These findings, though very preliminary, suggest that the combination of lenalidomide and dexamethasone may be a safe and promising initial therapy for PPCL patients, which can rapidly control the disease and could permit to perform following single patient-adapted therapeutic strategies. An update of this study, including molecular data, a larger number of patients and a longer follow-up, will be presented at the Meeting. Disclosures Musto: Janssen-Cilag: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide is approved in Italy for advanced multiple myeloma, not for plasma cell leukemia. This is a clinical trial registered at AIFA (Italian regulatory Agency for Drugs), EudraCT No. 2008-003246 28. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Morabito:Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria; Janssen-Cilag: Honoraria.


Author(s):  
Roma S Fourmanov ◽  
◽  
Annemiek Joosen ◽  
Lidwine Tick ◽  
Heleen S de Lil ◽  
...  

Background: Multiple myeloma is a relatively common type of plasma cell dyscrasia, in which monoclonal plasma cells proliferate. This frequently leads to anemia, renal failure, hypercalcemia and bone lesions. Primary plasma cell leukemia is a much rarer type of plasma cell dyscrasia, with measurable plasma cells in the blood circulation and usually more acute presenting signs. Case: A 57-year-old woman presented to the emergency department with dyspnea. Because of hypoxemia due to a hemoglobin concentration of 3.1 g/dL (1,9 mmol/L), asystole occurred, and cardiopulmonary resuscitation had to be started. The severe anemia turned out to be due to a primary plasma cell leukemia. Palliative treatment was started with combination chemotherapy with VTD (bortezomib, thalidomide and dexamethasone) with a very good partial response, after which she proceeded to an autologous stem cell transplantation with high dose melphalan conditioning. Conclusion: Primary plasma cell leukemia is a plasma cell dyscrasia with both resemblances and differences from the better-known multiple myeloma. It is less common, but presenting signs often are more acute and more severe. Currently there is no curative treatment. Keywords: Plasma cell leukemia; Hematological emergency; Multiple myeloma; VTD.


2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Carlos Fernández de Larrea ◽  
Robert Kyle ◽  
Laura Rosiñol ◽  
Bruno Paiva ◽  
Monika Engelhardt ◽  
...  

AbstractPrimary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.


2017 ◽  
Vol 17 (1) ◽  
pp. e49
Author(s):  
Elizabeta de los Angeles Rojas Ricardo ◽  
Irena Misiewicz-Krzeminska ◽  
Luis Corchete ◽  
Encarnación Fermiñán ◽  
Teresa Prieto ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (6) ◽  
pp. 907-912 ◽  
Author(s):  
Wilson I. Gonsalves ◽  
S. Vincent Rajkumar ◽  
Ronald S. Go ◽  
Angela Dispenzieri ◽  
Vinay Gupta ◽  
...  

Key Points Survival of patients with primary plasma cell leukemia has improved in recent years, but is still inferior to those patients with multiple myeloma. This survival benefit appears to be mainly in patients older than 65 years of age.


2021 ◽  
pp. 21-22
Author(s):  
Gaurav Sharma ◽  
Smita Sharma

Introduction: Primary Plasma Cell Leukemia (pPCL) is Plasma cell dyscrasia subtype which is rare and aggressive. It carries very poor prognosis. It has unique clinical and laboratory prole. Its rst clinical presentation is leukemia. Peripheral blood examination shows circulating mature looking yet clonal, plasma cells. On molecular and cytogenetic examinations, many aberrations are seen which are unique and make it a distinct entity different from traditional Multiple Myeloma (MM). Case presentation: 37 yr old Indian female presented with difculty in breathing for last 3 months and was initially evaluated for cardiac function & COVID-19 screening. Peripheral blood examination revealed circulating plasma cells. Bone marrow apirate conrmed the initial diagnosis of pPCL. She received BIODRONATE + Inj. BORTEZOMIB + Inj. CYCLOPHOSPHAMIDE + Tab Dexa and was advised for PETscan and skeletal survey. But due to nancial constraints, family decided to go for complete systemic workup in next phase of chemotherapy cycle. She was discharged with advise to be in close follow up and to complete her treatment cycles. Discussion: pPCL needs to be diagnosed promptly to formulate optimal intensive therapy. This atypical presentation with shortness of breath of rare entity of pPCLin such young age emphasizes the need for quick and thorough initial workup. Conclusion: Because of rarity of this disease, there is paucity of literature from India and especially the impact of the standard therapies in resource poor countries. Our case report highlights these challenges for conclusive management of this rare entity


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4898
Author(s):  
Katia Todoerti ◽  
Elisa Taiana ◽  
Noemi Puccio ◽  
Vanessa Favasuli ◽  
Marta Lionetti ◽  
...  

Mechanisms underlying the pathophysiology of primary Plasma Cell Leukemia (pPCL) and intramedullary multiple myeloma (MM) need to be further elucidated, being potentially relevant for improving therapeutic approaches. In such a context, the MM and pPCL subgroups characterized by t(11;14) deserve a focused investigation, as the presence of the translocation is mainly associated with sensitivity to venetoclax. Herein, we investigated a proprietary cohort of MM and pPCL patients, focusing on the transcriptional signature of samples carrying t(11;14), whose incidence increases in pPCL in association with an unfavorable outcome. In addition, we evaluated the expression levels of the BCL2-gene family members and of a panel of B-cell genes recently reported to be associated with sensitivity to venetoclax in MM. Moreover, transcriptional analysis of lncRNAs in the two clinical settings led to the identification of several differentially expressed transcripts, among which the SNGH6 deregulated lncRNA might be relevant in the pathogenesis and prognosis of pPCL with t(11;14). Overall, our data suggest that MMs and pPCLs with t(11;14) might be responsive to venetoclax based on different molecular programs, prompting further studies to elucidate better novel potential predictive biomarkers.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3938-3938 ◽  
Author(s):  
Luca Agnelli ◽  
Pellegrino Musto ◽  
Katia Todoerti ◽  
Marta Lionetti ◽  
Laura Mosca ◽  
...  

Abstract Abstract 3938 Primary plasma cell leukemia (PPCL) is a rare and very aggressive form of plasma cells dyscrasia, characterized by poorer outcome than multiple myeloma (MM). To provide insights into the biology of PPCL, we investigated 23 newly-diagnosed patients included in an open-label, multicenter, prospective, single arm, two-stage study aiming to explore efficacy and safety of lenalidomide and dexamethasone combination (LD) as first line therapy in previously untreated PPCL (median follow-up: 23 months; range 9–32). The primary endpoint of the study was the response rate, according to the criteria defined by International Myeloma Working Group, after 4-cycle therapy with LD over a 4-month schedule; among secondary endpoints were overall survival (OS) and eligibility to undergo autologous or allogeneic stem cells transplantation (SCT) after LD treatment. Herein, we took advantage of the FISH characterization and the microarray analysis of transcriptome, miRNome and copy number configurations of the PPCLs to investigate whether a correlation could exist between transcriptional features or allelic imbalances and clinical outcome. FISH was used to detect the main IGH translocations. The gene expression profiles of highly purified plasma cells from PPCLs cases were generated on GeneChip® Gene1.0 ST arrays. Expression values were normalized using robust multi-array average (RMA) procedure. MicroRNA profile were generated on Agilent Human miRNA Microarray V2. Expression values were extracted with Agilent Feature Extraction Software v10.1; quantile normalization was applied on raw data using R aroma.light package. GeneChip® Human Mapping 250K NspI arrays was used for genotyping. Copy number was estimated using circular binary segmentation and normalized on FISH data using R DNA.copy and FBN packages, respectively. To assess correlation between expression values and OS, R globaltest package was used to generate the linear regression model in which the distribution of the response variable is modeled as a function of the expression levels of each gene/miRNA. Our analysis indicated that all but three of the PPCLs had one among t(4;14) (13%), t(11;14) (39%) or MAF-associated translocation (35%). However, neither any of them nor any of the numerical alteration involving 1p, 6p, 8p, 13q, 14q, 16q, 17p (loss) and 1q (gain) as assessed by SNP-arrays were correlated with OS. As well, no correlation between response to treatment with LD and the prevalence of these cytogenetic alterations was evidenced. Of the 1145 most variable gene across the PPCL dataset and OS, 27 reached a highly significant correlation (P<.01) with OS. This 27-gene model was able to dissect the PPCL into two groups, one of which containing 6 cases with poorer outcome. In multivariate analysis, this model retained independency from all the cytogenetic alterations, as well as from age, sex, LDH levels, renal function and hematologic parameters. The 27-gene model was not independent of patients being subjected to autologous SCT, indicating that this therapeutic approach points definitively towards a more favorable outcome. Similarly, we assessed the relationship between each of the 114 most variable miRNAs across the dataset and OS. Two miRNAs reached a significant correlation (P<.01) with OS (miR-92a and miR-330–3p), allowing the division of samples into two groups with different outcome. In multivariate analysis, both retained independency from all the cytogenetic alterations [except del(8p) as regards miR-330–3p] and from other parameters, but not from autologous SCT. Finally, three genes (CYB5D2, EDEM3 and YIPF6) and four miRNAs (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with response to the first-line treatment with LD. Overall, this study represents the first integrated approach on a prospective study investigating genes and miRNAs expression and genotyping configuration in PPCL, indicating specific genes and miRNAs with relevance in the clinical outcome of the disease. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Driss Chaoui ◽  
Bruno Gallet ◽  
Philippe Genet ◽  
Babette Mbungani ◽  
Ahmad Al Jijakli ◽  
...  

High-output cardiac failure in multiple myeloma (MM) is related to arteriovenous shunting in bone infiltrate disease. We describe such a complication in a patient with primary plasma cell leukemia (pPCL) without bone disease. We review the mechanisms that could be involved. As previously described, traditional cardiac failure therapy is not effective. pPCL therapy should not be delayed.


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