OAB-047: Plasma cell disorder patients are left vulnerable after one dose of the BNT162b2 mRNA or the ChAdOx-nCOV-19 COVID-19 vaccines

Abstract Background Plasma cell leukemia (PCL) is a rare malignant plasma cell disorder that usually carries an aggressive course with a rapidly fatal outcome. Cytogenetic studies performed on plasma cell disorder are scarce and difficult because of the low proliferation rate of plasma cells. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical and structural chromosomal changes in PCL. Methods Interphase FISH (I-FISH) and two different specific probes for the regions containing 13q14.3 (D13S319) or 14q32 (IGHC/IGHV) were used to detect 13q14 deletion [del(13q14)] or IgH rearrangement in 22 PCL patients. For patients with IgH rearrangement, probes for IgH(JH) and 11q13 (CCND1) or 4p16 (FGFR3) were used to detect t(11;14)(q13;q32) or t(4;14)(p16;q32). Results Molecular cytogenetic aberrations were found in 19 of 22 (86.4%) PCL patients. Del(13q14) was detected in 13 cases (59.1%), and IgH rearrangement in 17 (77.3%) patients including 7 with t(11;14) and 3 with t(4;14). 14q32 rearrangement and 13q14 deletion were found concurrently in 11 cases (50%). Conclusions Chromosomal abnormalities are frequent in PCL. The most frequent aberrations among the cases was the 14q32 rearrangement and 13q14 deletion. I-FISH technique is useful to detect molecular cytogenetic aberrations and should be used in the routine evaluation of PCL.

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t(11;14) Plasma Cell Disorder Presents as a True Nonsecretory, Nonproducer Multiple Myeloma

Clinical Lymphoma & Myeloma ◽

10.3816/clm.2009.n.048 ◽

2009 ◽

Vol 9 (3) ◽

pp. 243-246 ◽

Cited By ~ 3

Author(s):

Wei Chen ◽

Mark McNamara ◽

Young Kim ◽

Qin Huang

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Plasma Cell Disorder ◽

Cell Disorder

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Fatty but starving marrow! Gelatinous transformation of bone marrow secondary to plasma cell disorder and all-trans-retinoic acid therapy: A report of two cases

South Asian Journal of Cancer ◽

10.4103/2278-330x.202563 ◽

2017 ◽

Vol 06 (01) ◽

pp. 040-041 ◽

Cited By ~ 2

Author(s):

Manu Goyal ◽

Anurag Gupta ◽

Swathi Yarlagadda ◽

Anil Handoo

Keyword(s):

Bone Marrow ◽

Retinoic Acid ◽

Plasma Cell ◽

Acid Therapy ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Plasma Cell Disorder ◽

Cell Disorder ◽

Gelatinous Transformation

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Monoclonal gammopathies of undetermined significance and smoldering myeloma

Acta Haematologica Polonica ◽

10.2478/ahp-2020-0035 ◽

2020 ◽

Vol 51 (4) ◽

pp. 193-202

Author(s):

Artur Jurczyszyn ◽

Ruth Hutch ◽

Anna Waszczuk-Gajda ◽

Anna Suska ◽

Katarzyna Krzanowska ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Standard Of Care ◽

Current Standard ◽

Malignant Plasma Cell ◽

Plasma Cell Disorder ◽

Smoldering Myeloma ◽

Cell Disorder ◽

Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) is a clonal plasma cell disorder implicated as a precursor of multiple myeloma (MM), while smoldering multiple myeloma (SMM) is a malignant plasma cell disorder without evidence of a myeloma-defining event(s) (MDE). This is a review article of both disorders outlining their current definition and management according to the current standard of care. We focus on the pathogenesis of MM and the role of MGUS and SMM in the development of active MM. MGUS is a benign disorder and, subsequently, is followed by observation. In contrast, for SMM, although the current standard of care is “watch and wait”, this paper will explore the circumstances in which treatment should be considered to prevent MDE.

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Using Machine Learning to Triage Bone Marrow Specimens to Improve Performance of Plasma Cell Disorder FISH Testing

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqy112.381 ◽

2018 ◽

Vol 150 (suppl_1) ◽

pp. S164-S165

Author(s):

Grace Linder ◽

Aliyah Sohani ◽

Jason Baron

Keyword(s):

Machine Learning ◽

Bone Marrow ◽

Plasma Cell ◽

Improve Performance ◽

Plasma Cell Disorder ◽

Cell Disorder

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T Cell Large Granular Lymphocytic Leukemia and Co-Existing Plasma Cell Disorders

Blood ◽

10.1182/blood-2018-99-114953 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5368-5368

Author(s):

M Hasib Sidiqi ◽

Mohammed A Aljama ◽

David S. Viswanatha ◽

David Dingli

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Mayo Clinic ◽

Monoclonal Gammopathy ◽

Specific Therapy ◽

Plasma Cell Disorders ◽

Plasma Cell Disorder ◽

Cell Disorder ◽

Lgl Leukemia

Abstract T cell large granular lymphocytic (T-LGL) leukemia has been reported to occur in patients with plasma cell disorders (PCD). We conducted a retrospective review of patients diagnosed with T-LGL leukemia and a PCD at the Mayo Clinic. 22 patients were identified with T-LGL leukemia and a plasma cell disorder. The T-LGL leukemia preceded the PCD in 18% (n=4), was synchronous in 50% (n=11) and diagnosed post plasma cell disorder in 32% (n=7) of patients. The PCD diagnosis varied and included monoclonal gammopathy of undetermined significance (MGUS, n=13), multiple myeloma (MM, n=5), smoldering multiple myeloma (SMM. N=2), lymphoplasmacytic lymphoma (LPL, n=1) and monoclonal gammopathy of renal significance (MGRS, n=1). 5 patients developed T-LGL leukemia after treatment for a PCD (4 with MM and 1 with LPL). 4 patients with MGUS progressed to a more aggressive disease, 3 to MM and 1 to LPL. Neutropenia (76%) and anemia (70%) were the most common clinical presentation. None of the patients had rheumatoid arthritis. Treatment for the TLGL was variable with a number of different agents used listed in Table 1. 45% (n=10) of patients had an indolent course and did not receive specific therapy for TLGL. 6 patients responded to a single line of therapy, all of whom received either cyclophosphamide or methotrexate based regimens. The remainder had a relapsing course with multiple lines of therapy including 2 patients that received splenectomy. Nine patients were identified as having symptomatic multiple myeloma and TLGL, Table 2. Four patients had progressed from a preexisting plasma cell disorder, 3 with MGUS and 1 with SMM. The diagnosis of TLGL preceded myeloma in 1 patient was concurrent in 4 and post myeloma diagnosis in 4 patients. Time to diagnosis of TLGL post myeloma ranged from 10 to 63 months. At time of LGL diagnosis neutropenia was present in 7/9 patients and anemia in 6/8 (data unavailable for 1 patient). Cytogenetics data was available in 7 patients. Hyperdiploidy was the most common abnormality (3/7) followed by deletion 13q (2/7), t(14;16) in 1 patient and 1q amplification in 1 patient. The majority of patients were treated with novel agents with 7 receiving bortezomib based therapy. 3 patients underwent autologous stem cell transplantation. Therapy directed at the TLGL was given to 4/9 patients. This consisted of a combination of cyclophosphamide and prednisone in 3/4 patients all of whom responded to therapy with resolution of cytopenias. One patient had TLGL with multiple relapses and required multiple lines of therapy including eventual splenectomy. 3 patients with TLGL diagnosed after the diagnosis of myeloma did not receive specific therapy directed at the TLGL. The clinical course of the TLGL in these 3 patients was indolent and did not appear to be affected by therapy for multiple myeloma. At last follow up 5 patients have died. After a median follow up of 76 months post TLGL diagnosis the median overall survival (OS) post TLGL diagnosis was not reached for the entire cohort. In the cohort of patients with multiple myeloma, median OS from time of myeloma diagnosis was 71 months. Median OS from time of TLGL diagnosis was not reached. T-LGL leukemia can present in patients with a variety of plasma cell disorders and occur at any stage of the disease process. It is an important differential to consider in patients with unexplained cytopenias that are incongruent with the activity of the plasma cell disorder. Disclosures Dingli: Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding.

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

Blood ◽

10.1182/blood.v108.11.5066.5066 ◽

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.

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A Pre-Existing Plasma Cell Disorder Occurs in Most Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v112.11.1693.1693 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1693-1693 ◽

Cited By ~ 2

Author(s):

Brendan M Weiss ◽

Pramvir Verma ◽

Jude Abadie ◽

Robin Howard ◽

Michael Kuehl

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Light Chain ◽

Medical Center ◽

Walter Reed Army Medical ◽

Cell Transplant ◽

Serum Samples ◽

Published Evidence ◽

Plasma Cell Disorder ◽

Cell Disorder

Abstract Background. A pre-existing plasma cell disorder (PPCD), such as monoclonal gammopathy of undetermined significance (MGUS), is thought to be present in at least one-third of patients presenting with symptomatic multiple myeloma (MM). However, no study has comprehensively evaluated the proportion of patients with MM that had a PPCD by laboratory testing on pre-diagnostic sera. Methods. The Walter Reed Army Medical Center autologous stem cell transplant database was cross-referenced with the Department of Defense Serum Repository (DoDSR) database, which catalogs serum samples collected every 2 years on over 4 million active-duty service members. All samples 32 years prior to the diagnosis of MM were retrieved. Serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and serum free light chain analysis (sFLC) (The Binding Site, San Diego, CA) were performed on all samples. A PPCD was defined as a positive SPEP, IFE or abnormal sFLC ratio. Results. Serum samples prior to the diagnosis of MM were available for 30/90 patients, and the median number of samples per patient was 3.5 (range, 1–14). The median age at diagnosis of MM was 48.1 yrs (29–67), with 96% male, 53% Caucasian, and 47% African-American. The Ig isotype of MM was IgG 76%, IgD 10%, light-chain 7%, and non-secretory 7%. A PPCD was detected in 27/30 patients (90%, 95% CI 74–97%). The initial PPCD was detected by sFLC alone in 6/27 (22.2%), IFE alone 2/27 (7.4%), SPEP+IFE 5/27 (18.5%), SPEP+IFE+sFLC 13/27 (48.1%) and IFE+sFLC 1/27 (3.7%). There were 4 patients whose only positive sera was 2.5–3.5 years prior to diagnosis, with all preceding sera negative. Conclusions. First, a pre-existing plasma cell disorder is present in most MM patients at least 2.5 years prior to diagnosis. Second, consistent with published evidence for a small fraction of patients with high risk MGUS, 4/30 patients were documented to progress rapidly through an MGUS phase to MM. Third, 4/4 patients with light chain only or non-secretory MM had a PPCD that was detected only by sFLC, thereby indicating that all these tumors are preceded by a light chain only or non-secretory PPCD.

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