scholarly journals Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia

2009 ◽  
Vol 2009 ◽  
pp. 1-2 ◽  
Author(s):  
Tommasina Guglielmelli ◽  
Roberta Merlini ◽  
Emilia Giugliano ◽  
Giuseppe Saglio
Keyword(s):  
Plasma Cell ◽  
Salvage Therapy ◽  
Plasma Cells ◽  
Single Case ◽  
Case Reports ◽  
Cell Leukaemia ◽  
First Line Therapy ◽  
Plasma Cell Leukaemia ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least2×109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.

2 Translocations, t(11;14) and t(l;6), in a Patient with Plasma Cell Leukaemia and 2 Populations of Plasma Cells

2009 ◽  
Vol 24 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Gösta Gahrton ◽  
Lore Zech ◽  
Kenneth Nillsson ◽  
Berit Lönnqvist ◽  
Anders Carlström
Keyword(s):  
Plasma Cell ◽  
Plasma Cells ◽  
Cell Leukaemia ◽  
Plasma Cell Leukaemia

Expression of CD126 (IL-R alpha) on Plasma Cells in Monoclonal Gammopathies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5066-5066
Author(s):  
Syed T. Mahmood ◽  
Shaji Kumar ◽  
Teresa K. Kimlinger ◽  
Jessica L. Haug ◽  
Michael Timm ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Subset ◽  
Primary Amyloidosis ◽  
Normal Plasma ◽  
Plasma Cell Disorders ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Abstract Background: IL-6 is important for proliferation and inhibition of apoptosis in malignant plasma cells. Understanding the role of IL-6 receptor alpha chain (CD126) in the pathogenesis of plasma cell disorders may help in developing future treatment therapies for these diseases. A previous study has shown that CD126 (alpha subunit of IL-6 receptor) is expressed distinctly in myeloma, monoclonal gammopathy of unknown significance (MGUS), and plasmacytomas when compared to normal. We performed this study in order to confirm and describe the expression of CD126 in different plasma cell disorders. Design and Methods: Using flow cytometry we assessed CD126 expression on clonal plasma cells from patients with Primary Amyloidosis (n=7), monoclonal gammopathy of undetermined significance (MGUS) (n=13), smoldering Myeloma (SMM) (n=19) and active Myeloma (n=22), as well as normal plasma cells (n=9). Plasma cells were identified by their characteristic CD38/45 expression. The expression of CD126 was separately analyzed on the CD45 positive and negative plasma cells. CD 126 expression was considered significant when more than 20% of the cells had expression. Results: CD126 expression was seen distinctly in plasma cell disorder plasma cells and not in normal plasma cells when all plasma cells were studied together. The highest expression percentages were found in Amyloid (28%) followed closely by MGUS 29(%), then SMM (23%), and Myeloma (12%) cells. The CD45 neg subset was similarly positive in the plasma cell disorder group. In this group, MGUS showed the highest expression percentage followed distantly by Amyloid, Myeloma, and SMM. The CD45 pos subset was uniformly positive in expression of CD126. If was found that this subset expressed higher levels of CD126 in all the studied plasma cell disorders and normal plasma cells when compared to the CD45 neg subset. Conclusion: The findings of this study confirm the increased expression of CD126 in plasma cell disorders when compared to normal plasma cells. The higher expression of CD126 in the CD45 pos plasma cell subset has not been previously described. In addition, the CD45 pos subset expressed higher levels of CD126 in all study groups when compared to the CD45 pos subset. This data contributes to the understanding of IL-6 receptor physiology and confirms the important role of the CD45 pos subset in the proliferation of neoplastic plasma cells. The findings are in accordance with the increased proliferative rates seen in the CD45 fraction of malignant plasma cells.

Rapid and Excellent Response to Hyper CVAD, Particularly with Thalidomide, in Plasma Cell Leukaemia and Long Term Remissions Following Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4963-4963 ◽  
Author(s):  
Vidhya Murthy ◽  
Anne Mwirigi ◽  
Susan Ward ◽  
Saad M.B. Rassam
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Stem Cell ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cell Leukaemia ◽  
First Line ◽  
Plasma Cell Disorders ◽  
Plasma Cell Leukaemia

Abstract Abstract 4963 Plasma cell leukemia [PCL] is the most aggressive form of plasma cell neoplasms constituting 2% to 4% of all cases of plasma cell disorders. The presentation may be primary or secondary from an existing multiple myeloma. Approximately 60 to 70% of cases are primary. Immunophenotype of PCL cells differs from the most of other myelomas with more frequent expression of CD20 antigen (50% vs. 17%), and lack CD56 antigen present on the majority of multiple myeloma cells. PCL patients have a higher presenting tumor burden with higher frequencies of anaemia, organomegaly, renal impairment, increased levels of serum lactate dehydrogenase (LDH), β-2 microglobulin and plasma cell proliferative activity. Prognosis of PCL is exceptionally poor with median survival of 6.8 months for patients with primary PCL and 1.3 months for patients with secondary PCL. It responds poorly to conventional myeloma treatment and polychemotherapy approach has yielded some short lived success. Recently, bortezomib has been reported first line in combination with other agents with good initial response. In the UK, bortezomib is not approved as a first line treatment for plasma cell disorders. The Hyper CVAD regimen (fractionated high dose cyclophosphamide and dexamethasone with infusional vincristine and adriamycin) has been developed for acute lymphoblastic leukaemia by the M D Anderson group and has also been shown to be effective in other aggressive B-cell disorders such as mantle cell and Burkitt's lymphoma. There are few single patient anecdotal reports of its efficacy in plasma cell leukaemia. We report three cases of plasma cell leukaemia successfully induced with limited courses of Hyper CVAD chemotherapy and long term remissions achieved with stem cell transplantation. Two men aged 53 and 56 and one woman aged 40 presented with PCL. All were anaemic (median Hb 8.5 g/dl), had impaired renal function, raised beta-2 microglobulin, creatinine, circulating plasma cells and plasmablasts and almost total marrow replacement by plasma cells. Two had IgG kappa paraprotein and one had light chains only. All had weak CD56 expression and two, where tested, were CD38 positive. Cytogenetic analysis was positive in one patient with t(4,14). All received hydration, bisphosphonate and allopurinol preparation before induction with the Hyper CVAD regimen. Two, given Thalidomide as well, achieved morphological complete remission (CR) after one course of therapy with marked reduction of paraprotein and normalisation of renal function. They received one further course of Hyper CVAD before receiving a Melphalan conditioned autlogous stem cell (ASCT) followed by a reduced intensity conditioning (RIC) sibling allogeneiec transplant in one patient. She remains in CR and full donor chimerism 11 months post SCT. The other is being prepared for ASCT to be followed by a RIC voluntary unrelated transplant. The patient with light chain disease achieved partial response (20% plasma cells in the bone marrow) after one course of Hyper CVAD without Thalidomide but a complete response after the second. He was consolidated with a third cycle, followed by a course of mini BEAM and then a RIC sibling allogeneic SCT. He had an early relapse 12 months following his SCT but responded to a course of donor lymphocyte infusion (DLI) and remains in CR 8.5 years from his SCT. Discussion To our knowledge, this is the largest series using this approach in PCL reported in the literature. PCL is a rare but aggressive disease with poor response to conventional therapy and short survival. Hyper CVAD appears to be highly effective in inducing a good response after 1-2 cycles of therapy particularly when combined with thalidomide. It appears that PCL is sensitive to the graft-versus-myeloma effect with long lasting remissions after allogeneic SCT and DLI therapy. Disclosures Rassam: Johnson and Johnson: Research Funding.

scholarly journals Multiple Myeloma and Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Zeinab A. Issa ◽  
Mira S. Zantout ◽  
Sami T. Azar
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Malignant Plasma Cell ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Multiple myeloma is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers. It is characterized by accumulation of clonal plasma cells, predominantly in the bone marrow. The prevalence of type 2 diabetes is increasing; therefore, it is expected that there will be an increase in the diagnosis of multiple myeloma with concomitant diabetes mellitus. The treatment of multiple myeloma and diabetes mellitus is multifaceted. The coexistence of the two conditions in a patient forms a major challenge for physicians.

Biology of the Transition of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma

1998 ◽  
Vol 5 (3) ◽  
pp. 209-217 ◽  
Author(s):  
John A. Lust ◽  
Kathleen A. Donovan
Keyword(s):  
Multiple Myeloma ◽  
Adhesion Molecules ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Therapeutic Strategies ◽  
Plasma Cell Disorder ◽  
Novel Therapeutic Strategies ◽  
Cell Disorder ◽  
Undetermined Significance

Background Approximately 25% of patients with monoclonal gammopathy of undetermined significance (MGUS) eventually develop multiple myeloma (MM) or a related plasma cell disorder that is universally fatal. In this report, we examine the changes that occur in the clonal plasma cell that are likely to be important in the progression of MGUS to active myeloma. Methods Studies that investigate the mechanisms involved in the multistep pathogenesis of monoclonal gammopathies are reviewed. Cytokines such as IL- 6 and IL-1β, adhesion molecules, viruses, and oncogenes including ras, bcl-2, Rb, and p53 are discussed. Results IL-1β is produced by plasma cells from virtually all MM patients but is undetectable in most MGUS patients. IL-1β has potent osteoclast activating factor activity, can increase the expression of adhesion molecules, and can induce paracrine IL-6 production. The increased production of adhesion molecules could explain why myeloma cells are found predominantly in the bone marrow. Subsequently, these “fixed” monoclonal plasma cells could now stimulate osteoclasts through the production of IL-1β and paracrine generation of IL-6 resulting in osteolytic disease. With continued progression of the myeloma, the monoclonal plasma cells may later acquire the ability to produce IL-6 in an autocrine fashion that will be manifested clinically by an elevated labeling index. Conclusions A better understanding of the progression of MGUS to myeloma may lead to novel therapeutic strategies to prevent the development of MM.

Plasma cell leukaemia with t(11;14) not responsive to venetoclax

2021 ◽  
Vol 14 (1) ◽  
pp. e238641
Author(s):  
Mohammed Isaac Abu Zaanona ◽  
Priyank Patel
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
In Situ Hybridisation ◽  
Haematopoietic Stem Cell ◽  
Successful Outcome ◽  
Cell Leukaemia ◽  
Plasma Cell Leukaemia ◽  
History Of ◽  
Early Phase Clinical Trials

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.

scholarly journals Primary Plasma Cell Leukaemia: Case report and review of the literature

2018 ◽  
Vol 18 (3) ◽  
pp. 397
Author(s):  
Sarika Singh ◽  
Ashutosh Rath ◽  
Surekha Yadav
Keyword(s):  
Case Report ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Renal Involvement ◽  
Specific Treatment ◽  
Peripheral Blood Smear ◽  
Cell Leukaemia ◽  
Plasma Cell Dyscrasia ◽  
Diagnostic Features ◽  
Plasma Cell Leukaemia

Plasma cell leukaemia (PCL) is one of the most aggressive and rarest forms of plasma cell dyscrasia. However, the diagnostic criteria for this condition have not yet been revised and there is no specific treatment to significantly improve the course of the disease. We report a 69-year-old male who presented to the Lok Nayak Hospital, New Delhi, India, in 2017 with dyspnoea and chest pain. A peripheral blood smear showed an absolute plasma cell count of 2.16 × 109/L. A bone marrow examination showed 61% atypical plasma cells exhibiting kappa light chain restriction. Biochemical investigations were consistent with a diagnosis of primary PCL with renal involvement. Bortezomib-based chemotherapy was initiated, which resulted in an improvement in the patient’s haematological and biochemical parameters. This case report includes a comprehensive review of the clinical and diagnostic features, pathobiology and treatment of PCL.Keywords: Plasma Cell Leukemia; Multiple Myeloma; Plasma Cells; Case Report; India.

scholarly journals Bortezomib Overcomes Poor Prognosis Conferred By High Sictp in Untreated Plasma Cell Disorders

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5492-5492
Author(s):  
Akira Honda ◽  
Yu Oyama ◽  
Kazuhiro Toyama ◽  
Mineo Kurokawa
Keyword(s):  
Pharmaceutical Company ◽  
Plasma Cell ◽  
Research Funding ◽  
Poor Prognosis ◽  
Proteasome Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Introduction To date, various biochemical markers of bone remodeling have been investigated in multiple myeloma (MM) patients. Serum C-terminal telopeptide of type I collagen (sICTP) is a well-known biochemical marker of bone remodeling. Although several reports showed the relationship between a high level of sICTP and poor prognosis in MM patients, little is known about the efficacy of bortezomib in high sICTP patients. In this single center retrospective study, we assessed the association between sICTP and the prognosis of plasma cell disorder patients, particularly in patients firstly treated with bortezomib-containing regimen. Methods We retrospectively reviewed untreated MM and other plasma cell disorder patients who were diagnosed at The University of Tokyo Hospital between January 2001 and December 2016. The clinical data of patients whose sICTP was measured before the start of first-line therapy were collected. Serum ICTP was measured at diagnosis in 59 patients: 56 patients with MM, 2 patients with plasmacytoma, and 1 patient with light chain amyloidosis. These patients were divided into high sICTP and low sICTP groups according to the median of sICTP level. Additionally, patients firstly treated with bortezomib-containing regimen were divided into two groups according to the median of sICTP level. Overall survival (OS) and bone fracture-free survival (FFS) were calculated from initiation of the first-line therapy using the Kaplan-Meier method and log-rank tests. Results In 59 patients, the median age was 65 years (range, 45-85 years) and median follow-up was 387 days (range, 22-2019 days). Thirty-three patients (55.9%) were male and 26 (44.1%) were female. IgG was the most frequent subtype of M-protein (58%), followed by IgA (19%), Bence Jones proteins (19%), and IgE (3%). International scoring system classified 16 (27.1%), 24 (40.7%), and 19 (32.2%) as stage I, II, and III, respectively. Levels of sICTP were high in 31 (52.5%) patients and low in 28 (47.4%) patients. The level of sICTP differed significantly (P<0.01) between the groups ISS stage I, II, and III, and increased parallel with the progression of the disease. Twenty-eight (47.4%) patients were administered bortezomib-containing regimen as first-line therapy, which was consisted of BD (bortezomib + dexamethasone), VCD (bortezomib + cyclophosphamide + dexamethasone), and VMP (bortezomib + melphalan + prednisolone). The remaining 31 (52.5%) patients were administered without proteasome inhibitors as first-line therapy. Nineteen patients (32.2%) achieved at least very good partial response after first-line therapy and 9 (15%) patients fractured after start of first-line therapy. Median OS for the entire cohort was 1874 days. In the Kaplan-Meier survival analysis, high sICTP (above upper limit: 6.0 mg/l) significantly associated with worse 2-year OS (63% versus 96%, P=0.02) and worse 2-year FFS (51% versus 86%, P=0.04). Serum ICTP may be a useful marker to predict survival and future bone fracture in our cohort, and these results are consistent with previous reports. Interestingly, in the patients firstly treated with bortezomib-containing regimen, the level of sICTP had no effect on 2-year FFS (90% with high sICTP versus 100% with low sICTP, P=0.53) and 2-year OS (95% with high sICTP versus 100% with low sICTP, P=1). Conclusion In general, high sICTP is considered to be a poor prognostic factor in MM patients, and similar results were also demonstrated in our cohort. Importantly, our data suggest that bortezomib may overcome poor prognosis conferred by high sICTP in plasma cell disorder patients. Further studies based on more cases are warranted to elucidate the efficacy of bortezomib in high sICTP patients. In addition, further studies on other proteasome inhibitors, such as carfilzomib or ixazomib are also needed. Disclosures Honda: Hitachi, Ltd.: Speakers Bureau. Toyama:Bristol-Myers Squibb: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Celgene K.K.: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau. Kurokawa:Shire Japan K.K.: Speakers Bureau; Novartis Pharma K.K.: Research Funding; Daiichi Sankyo Conpany: Speakers Bureau; Pfizer Japan Inc.: Research Funding; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Celgene K.K.: Consultancy, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co.,Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Yakult Honsha Company: Speakers Bureau; Bioverativ Japan ltd.: Consultancy; Chugai Pharmaceutical Company: Consultancy, Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; MSD K.K.: Consultancy, Research Funding, Speakers Bureau; Shionogi & Co., Ltd: Consultancy, Honoraria; Teijin Limited: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Janssen Pharmaceutical K.K.: Speakers Bureau.

scholarly journals Absence of a common founder mutation in patients with co-occurring myelodysplastic syndrome and plasma cell disorder

Blood ◽  
2020 ◽  
Author(s):  
Monika Klimkowska ◽  
Yasuhito Nannya ◽  
Charlotte E Gran ◽  
Robert Mansson ◽  
Iyadh Douagi ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Founder Mutation ◽  
Case Reports ◽  
Risk Groups ◽  
Epidemiological Studies ◽  
University Hospital ◽  
Whole Exome ◽  
Common Founder ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Epidemiological studies have demonstrated an increased incidence of MDS in patients with plasma cell disorder (PCD) i.e. multiple myeloma (MM) or MGUS and several case reports / series of co-occurring MDS and PCD have been published. The underlying pathogenesis for this condition, and if the two diseases share a common genetic lesion remains unknown. Here, we describe a cohort of 27 consecutive patients with co-occurring MDS and MM (n=6), MGUS (n=20) or plasmocytoma (n=1), diagnosed at the Karolinska University Hospital. In 5 patients, the diagnosis of MGUS preceded the diagnosis of MDS , in one patient the MDS diagnosis preceded PCD, and in 21 patients MDS and PCD were diagnosed at the same time. There was a preponderance for lower-risk MDS subgroups with only 3 patients belonging to the IPSS-R high / very high risk groups. Median overall survival for the whole cohort was 44 months. The most common mutations were TET2, SRSF2 and SF3B1. To identify potential common founder clones, we performed whole exome sequencing on isolated bone marrow myeloid-, plasma- and T-cells from 9 patients. In none of the patients, we could detect a common founder mutation and the two diseases have likely emerged from separate clones.

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