scholarly journals A Diagnostic Dilemma: Waldenström's Macroglobulinemia/Plasma Cell Leukemia

2012 ◽  
Vol 2012 ◽  
pp. 1-3
Author(s):  
Bhawna Sethi ◽  
K. S. Butola ◽  
Yogesh Kumar
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Elevated Serum ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
Waldenström’S Macroglobulinemia ◽  
Cardiorespiratory Failure ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Waldenström's macroglobulinemia is a B-cell neoplasm characterized by infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM monoclonal gammopathy. It is an uncommon disease with overall incidence of approximately 3 per million persons per year, accounting for approximately 1% to 2% of all hematologic cancers. It has only one-sixth the estimated prevalence of plasma cell myeloma. Disease symptoms can be due to infiltration of bone marrow and other tissue sites by malignant lymphoplasmacytic cells or due to the effects of elevated serum IgM levels. However, patients may present with constitutional symptoms only or may be asymptomatic. In our case, patient presented with chief complaints of fatigability and dyspnoea and was misdiagnosed as plasma cell leukemia on peripheral blood film and bone marrow morphology, but turned out to be a case of Waldenström's macroglobulinemia on cytoflorometry. The patient was referred for chemotherapy but expired on 10th day of admission. The suspected cause of death was cardiorespiratory failure.

Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenström's macroglobulinemia.

1993 ◽  
Vol 11 (5) ◽  
pp. 914-920 ◽  
Author(s):  
M A Gertz ◽  
R A Kyle ◽  
P Noel
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Subcutaneous Fat ◽  
Immunoglobulin M ◽  
Entire Group ◽  
Waldenström’S Macroglobulinemia ◽  
Cardiac Amyloid ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

PURPOSE To determine the natural history of amyloidosis associated with Waldenström's macroglobulinemia and immunoglobulin M (IgM) monoclonal gammopathy. PATIENTS AND METHODS From January 1968 to September 1990, 50 patients with a serum IgM monoclonal protein and biopsy-proven amyloidosis were evaluated at the Mayo Clinic. There were 32 men and 18 women (age range, 43 to 93 years). RESULTS Percentages of patients presenting with cardiac, renal, hepatic, and pulmonary amyloid were 44%, 32%, 14%, and 10%, respectively. Forty-two percent of the patients had an M protein value greater than 1.5 g/dL, and 12% had an M component greater than 3 g/dL. Subcutaneous fat, rectum, and bone marrow showed amyloid in 84%, 72%, and 50%, respectively, providing a simple technique for diagnosing amyloidosis. The bone marrow biopsy was consistent with Waldenström's macroglobulinemia in 10, a plasma-cell proliferative disorder in 10, and lymphoma or a lymphoproliferative disorder in 11; results were normal, nondiagnostic, or hypercellular in 17. Forty-three of 50 patients died. The median survival of the entire group was 24.6 months. Fifty-three percent of deaths were due to cardiac amyloid, 12% to respiratory failure, 7% to macroglobulinemia, 7% to liver failure, and 7% to kidney failure. CONCLUSION The presence of amyloid cardiomyopathy and an increased creatinine concentration at diagnosis had an adverse impact on survival. Of the 22 patients who presented with cardiomyopathy, the median survival was 11.1 months, with only two surviving longer than 5 years. The median survival of the 28 patients without cardiomyopathy at diagnosis was 27 months, with eight 5-year survivors (P = .013). All eight amyloid deposits studied stained for Ig light chain, indicating that this amyloidosis is of the primary (AL) type.

B-Lymphocyte Stimulator (BLyS) Is Highly Expressed in Waldenstrom’s Macroglobulinemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2291-2291
Author(s):  
Stephen M. Ansell ◽  
Deanna M. Grote ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
Robert A. Kyle ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Waldenström’S Macroglobulinemia ◽  
B Lymphocyte Stimulator ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia ◽  
Normal Controls

Abstract Waldenstrom’s macroglobulinemia is a serious and frequently fatal illness, however many of the mechanisms leading to this disease are not yet known. It is clear, however, that there is dysregulation of the balance between cell proliferation and programmed cell death. BLyS (B-lymphocyte stimulator) is a newly identified TNF family member expressed by monocytes, macrophages, and dendritic cells. BLyS has been shown to be critical for maintenance of normal B cell development and homeostasis, and has been found to stimulate lymphocyte growth. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B-cells. Studies of the effects of BLyS on B cell physiology have shown that it also regulates immunoglobulin secretion. To determine the relevance of the BLyS receptor-ligand system in Waldenstrom’s macroglobulinemia, we examined malignant B cells from 5 patients with Waldenstrom’s macroglobulinemia for their ability to bind soluble BLyS and for the expression of the known BLyS receptors, TACI, BAFF-R, or BCMA. The malignant B cells were found to bind BLyS and express BAFF-R and TACI. BCMA expression was undetectable. We then determined the expression of BLyS in bone marrow specimens from 5 patients with Waldenstrom’s macroglobulinemia by immunohistochemistry and compared it to the expression in 5 normal bone marrow specimens. The lymphoplasmacytic cell infiltrate in the bone marrow of patients with Waldenstrom’s macroglobulinemia showed significantly increased BLyS expression. We further determined the serum BLyS levels by ELISA in stored serum specimens from patients with Waldenstrom’s macroglobulinemia (n=20), and compared them to serum BLyS levels in other patients with lymphoplasmacytic lymphoma without elevated immunoglobulin levels (n=10) and to serum levels in normal controls (n=50). Serum BLyS levels in Waldenstrom’s patients (mean: 49.6ng/ml) as well as those in patients with lymphoplasmacytic lymphoma (mean; 46.7ng/ml) were significantly higher than normal controls (mean 12.6ng/ml). In conclusion, we have demonstrated that malignant B cells from patients with Waldenstrom’s macroglobulinemia express the receptors for BLyS and can bind soluble BLyS. Furthermore, we have found that serum BLyS levels are significantly elevated in patients with Waldenstrom’s macroglobulinemia when compared to controls. Strategies to inhibit BLyS may potentially have significant therapeutic efficacy in Waldenstrom’s macroglobulinemia.

Abnormal Expression of the Plasma Cell Differentiation Factor X-Box Protein 1 (Xbp-1) in Waldenstrom’s Macroglobulinemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1003-1003 ◽  
Author(s):  
Lian Xu ◽  
Xavier Leleu ◽  
Zachary R. Hunter ◽  
Daniel D. Santos ◽  
Allen W. Ho ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Plasma Cell ◽  
Waldenström’S Macroglobulinemia ◽  
Plasma Cell Differentiation ◽  
Abnormal Expression ◽  
Healthy Donors ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract INTRODUCTION: Xbp-1 is a ubiquitously expressed basic leucine zipper protein which serves as key transcription factor for plasma cell differentiation and immunoglobulin production. XBP-1 mRNA undergoes splicing at an IRE-1a specific cleavage site to produce a spliced form (Xbp-1s) which due to a frame shift results in a more stable and potent transcription factor than the unspliced form (Xbp-1us). Previous observations demonstrated that Xbp-1 was highly expressed in multiple myeloma (MM), though its expression in other B-cell disorders including Waldenstrom’s macroglobulinemia (WM) remains to be clarified. METHODOLOGY: In this study, we investigated the different forms of Xbp-1 in CD19+ selected bone marrow (BM) cells from 61 patients with the consensus panel definition of WM using semi-quantitative PCR analysis. CD19+ selected BM cells from 6 healthy donors, and CD138+ selected BM cells from 4 MM patients were used as controls. All RT-PCR results were normalized to b-actin levels. Sequencing of Xbp-1 in CD19+ selected LPC was also performed for 20 WM patients. RESULTS: In 9/61 (15%) WM patients, Xbp-1 transcripts were undetectable. Among WM patients expressing Xbp-1, as well as all MM patients evaluated, higher levels of XBP-1us were observed in comparison to normal healthy donors (p=0.001). Decreased XBP-1s transcript levels were also observed among WM and MM patients versus healthy donors, but did not reach statistical significance. Sequence analysis of Xbp1 in CD19+ selected BM LPC demonstrated variants 10/20 WM patients in exon 1 that are currently under investigation. CONCLUSIONS: Abnormal expression of Xbp-1 is common in patients with WM, and includes loss of expression, and aberrations in splice patterns. The genetic basis for these findings is under investigation.

Histone Deacetylase Inhibitors Demonstrate Significant Preclinical Activity as Single Agents, and in Combination with Bortezomib in Waldenstrom's Macroglobulinemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4785-4785
Author(s):  
Jenny Sun ◽  
Lian Xu ◽  
Hsiuyi Tseng ◽  
Bryan Ciccarelli ◽  
Mariateresa Fulciniti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Histone Deacetylase Inhibitors ◽  
Conflicts Of Interest ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Waldenström’S Macroglobulinemia ◽  
Over Expression ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Abstract 4785 Waldenstrom's Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by bone marrow infiltration of CD19+ cells and production of a monoclonal IgM protein. Despite advances in treatment, WM remains incurable. As part of these efforts we sought to define the role of HDAC-inhibitors in WM. Gene expression profiling of bone marrow CD19+ cells from 30 WM patients and 10 healthy donors showed over-expression of HDAC4, HDAC9, and Sirt5 in WM patients. Evaluation of the HDAC inhibitors suberoylanilide hydroxamic acid (SAHA or Vorinostat), Trichostatin A (TSA), LBH-589 (Panobinostat), and sirtinol demonstrated dose dependent killing of BCWM.1 cells with IC50 of 3.5 uM, 70 nM, 0.8 uM, and 30 uM, respectively, whilst the combination of these agents with bortezomib resulted in at least additive tumor cell killing. TSA is more potent than bortezomib in inducing apoptosis in primary WM tumor cells in patients with prior treatment. TSA and bortezomib showed synergistic effect in 25% of the patients samples tested. We also observed that TSA and bortezomib-induced apoptosis of BCWM.1 cells depended on the activation of a similar set of caspases. Conversely, changes in cell cycle regulators were distinctly different between TSA and bortezomib treated BCWM.1 cells. The results of these studies demonstrate over-expression of distinct members of HDAC in WM cells, and provide a framework for the examination of HDAC-inhibitors as monotherapy, as well as combination therapy with bortezomib in the treatment of WM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Waldenstrom’s Macroglobulinemia and Peripheral Neuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes with a Bleeding Diathesis and Rash

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
S. Haider ◽  
T. Latif ◽  
A. Hochhausler ◽  
F. Lucas ◽  
N. Abdel Karim
Keyword(s):  
Bone Marrow ◽  
Peripheral Neuropathy ◽  
Monoclonal Gammopathy ◽  
Poems Syndrome ◽  
Waldenström’S Macroglobulinemia ◽  
Excessive Bleeding ◽  
Skin Changes ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

We report a case of a 29-year-old male who presented with paraesthesia and skin lesions with excessive bleeding after skin biopsy leading to hematology consultation. He was found to have prolonged partial thromboplastin time (PTT) and monoclonal gammopathy on serum protein electrophoresis (SPEP). He experienced excessive bleeding leading to hospitalization after bone marrow biopsy and required blood transfusion. He was diagnosed with Waldenstrom's Macroglobulinemia (WM), based on the presence of IgM-κtype monoclonal (M) protein and infiltration of lymphoplasmacytic cells identified in bone marrow aspirates. He was noticed to have features of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome). This is a very rare case of WM with POEMS syndrome which responded to chemotherapy using bortezomib, steroids, and rituximab.

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