Monoclonal Proteins in Elderly Patients with Osteoporosis

Abstract Background: Monoclonal proteins (M-proteins) and osteoporosis are both common in the elderly. For most patients with M-proteins and osteoporosis, the protein represents monoclonal gammopathy of undetermined significance (MGUS). In rare cases, the M-protein signifies multiple myeloma, and the osteoporosis is secondary to myeloma bone disease. Thus, it is important to identify M-proteins in patients presenting with osteoporosis, and to consider whether such patients could have myeloma. Objectives: To determine the prevalence of M-proteins in patients age 65 and older referred to the Osteoporosis Clinic at BC Womens’ Hospital in Vancouver, BC, to review the management of patients with M-proteins, and to determine if the characteristics of patients with M-proteins differ from those without M-proteins. Methods: A retrospective chart review of patients age 65 and older referred to the Osteoporosis Clinic at BC Women’s Hospital from April 2006 – March 2008 was performed. Patient demographics, CBC, creatinine, calcium, serum protein electrophoresis, bone marrow biopsy results if available, bone density, presence of osteolytic lesions, fractures, and clinical diagnoses were recorded. Results: 224 charts were reviewed from 205 female and 19 male patients. Osteoporosis was diagnosed in 202 patients. 16 patients (7.1%) had an M-protein. The concentration of the M-protein ranged from <1 g/L to 11 g/L. The characteristics of patients with and without M-proteins are presented in Table 1. Seven patients (3.1%) had background suppression of immunoglobulins with no detectable M-protein. Eight patients (50%) with M-protein had documented vertebral compression fractures compared to 70 patients (38%) with no M-protein. Five patients (31%) with and 41 patients (23%) without M-proteins had other fragility fractures. One patient with an M-protein had a mild anemia. All patients with M-proteins had normal calcium and creatinine. One patient with an M-protein was already known to have a B-cell lymphoma. Two patients were referred to a hematologist. One patient had a bone marrow biopsy and was diagnosed with multiple myeloma. No other patients were thought to have multiple myeloma, but no other bone marrow biopsies were performed. No extra investigations were done in the patients with hypogammaglobulinemia in the absence of an M-protein. Table 1. Characteristics of patients with and without M-proteins. Characteristic No M-Protein (n=201) M-Protein (n=16) Female (%) 184 (91) 14 (88) Age Mean ± SD 74 ± 7.7 77 ± 9.1 Osteoporosis (%) 182 (90) 15 (94) BD Mean ± SD −2.6 ± 1.2 −2.4 ± 1.5 Vertebral # (%) 70 (35) 8 (50) Fragility # (%) 41 (20) 5 (31) Conclusions: M-proteins are more common in elderly patients with osteoporosis than in the general population. Patients with osteoporosis and M-proteins may have an increased risk of fracture compared to such patients without M-proteins. In elderly patients with osteoporosis and M-proteins, it seems likely that the most common plasma cell dyscrasia is MGUS. However, the prevalence of multiple myeloma in these patients is unclear, and a standard approach to investigation is needed. While it is important not to miss a diagnosis of multiple myeloma, it is also prudent to avoid unnecessary invasive procedures (ie. bone marrow biopsies) in elderly and sometimes frail patients.

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The Certainty of a Post-Bone Marrow Diagnosis: A Study of the Yield of Bone Marrow Biopsies in a Community Hospital Setting

Blood ◽

10.1182/blood-2020-142032 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-35

Author(s):

Manasi M. Godbole ◽

Peter A. Kouides

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Bone Marrow Biopsy ◽

Fever Of Unknown Origin ◽

Conflicts Of Interest ◽

Diagnostic Yield ◽

Hospital Setting ◽

Unknown Origin ◽

Nutritional Deficiencies ◽

Bone Marrow Biopsies

Introduction: Most studies on the diagnostic yield of bone marrow biopsy including the one by Hot et al. have focused on the yield of bone marrow biopsies in diagnosing the source of fever of unknown origin. However, there have not been any studies performed to our knowledge looking at overall practice patterns and yield of bone marrow biopsies for diagnoses other than fever of unknown origin. We aim to determine the most common indications for performing bone marrow biopsies in a community-based teaching hospital as well as the yield of the biopsies in patients with specified and unspecified pre-test indications to estimate the rate of uncertain post-test diagnoses. Methods: We performed a retrospective data collection study at Rochester General Hospital, NY. A comprehensive search was conducted in our electronic medical data to identify all patients who underwent bone marrow biopsies over a 5 year period from January 2011 - December 2016 for indications other than fever of unknown origin. Patient data including demographics, pre-bone marrow biopsy diagnosis and post-bone marrow diagnosis was obtained. All patients above the age of 18 who underwent bone marrow biopsy for indications other than fever of unknown origin or follow up treatment of a hematological malignancy were included. Results: A total of 223 biopsies were performed. The median age was 59 years (age range- 23-95). One hundred and sixteen patients were male and 107 were female. The most common indications for performing bone marrow biopsy were evaluation of the following possible conditions: multiple myeloma (n=54), myelodysplastic syndrome [MDS] (n=47), lymphoma (n=28) and leukemia (n=18) as well as non-specific indications such as pancytopenia (n=40), anemia (n=22) and thrombocytopenia (n=11). The proportion of cases confirmed by bone marrow biopsy was 45/54 (83%) with the pre-marrow diagnosis of multiple myeloma, 34/47 cases (72%) with the pre-marrow diagnosis of MDS, 15/18 (83%) with the pre-marrow diagnosis of leukemia and 13/28 (46%) in those with the pre-marrow diagnosis of rule out lymphoma. Thirteen cases (18%) with possible MDS had post-bone marrow diagnoses of leukemia, anemia of chronic disease, myelofibrosis or medication-related changes. Five out of twenty two cases (23%) for anemia and 3/11 cases (27%) for thrombocytopenia without otherwise specified pre-bone marrow etiology had uncertain diagnosis after bone marrow biopsy. Conclusion: In about a fifth of patients necessitating a bone marrow, the diagnosis is discordant and can be surprising. It is also worth reporting that in these discordant results, non-hematological causes such as medications, anemia due to chronic diseases or conditions such as cirrhosis or splenomegaly from other etiologies were among the final diagnoses. Interestingly, 20% of the patients with unspecified pre-bone marrow diagnoses such as anemia or thrombocytopenia in our study had an unclear post-bone marrow diagnosis despite undergoing bone marrow biopsy. Our findings are a reminder that the bone marrow exam does not always lead to a definitive diagnosis and the need by exclusion to include in the differential non-hematological etiologies such as nutritional deficiencies, chronic kidney disease or autoimmune disorders. Disclosures No relevant conflicts of interest to declare.

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Bone Effect of Botezomib in Patients with Relapse and Smoldering Myeloma; A Computer Assisted Image Analysis Study of Bone Marrow Core Biopsies,

Blood ◽

10.1182/blood.v118.21.3996.3996 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3996-3996

Author(s):

Mohamed E Salama ◽

Graham E. Wagner ◽

Tamara Berno ◽

Jessica Kohan ◽

Fenghuang Zhan ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Image Analysis ◽

Bone Marrow Biopsy ◽

Computer Assisted ◽

Weekly Dose ◽

Bone Marrow Biopsies ◽

Bortezomib Treatment ◽

Smoldering Myeloma ◽

Bone Effect

Abstract Abstract 3996 Background: Bone loss and related complications including bone pains, fractures and hypercalcemia are major causes of morbidity and mortality in multiple myeloma (MM) patients. Bone growth/loss (Bone mineral densitometry) can be monitored by dual x-ray absorptiometry (DXA) in patients with smoldering myeloma (SMM). We previously reported a novel quantitative method to asses trabecular volume (TV) using whole scanned slides and image analysis (WSI) obtained from bone marrow biopsy (Teman et al. 2010). This method provides a low cost reproducible mean to assess TV in archival paraffin embedded biopsy materials. Velcade has been shown to produce an anabolic bone effect in relapsed/refractory MM patients and in this study, we examine the effect of low-dose bortezomib (Velcade) in SMM patients using the WSI methodology. Methods: Bone marrow biopsy slides obtained before, during and after bortezomib treatment were used to evaluate TV. H&E stained core biopsy slides were scanned using Scan Scope XT system (Aperio Technologies, Vista, CA) into digital whole slide images that is viewable on Aperio Image Scope. We developed classifier algorithms using Genie (Aperio) pattern recognition image analysis software (PRIA) that were adept at identifying bone, hematopoietic tissue, and clear glass. The calculated bone area (TV) was represented as a ratio of the total hematopoietic area for each biopsy event. Slides were excluded if the analysis available area was less than 6mm2 or could not be classified correctly to the satisfaction of the pathologist Mixed-effects models were used to compare bone TV/hematopoietic ratios (HR) over time and between the different groups, as well as assess any correlation with that ratio and light chain, B-2-microglobulin, and plasma cell levels. Results were considered statistically significant if p<0.05. Results: Slides from 253 consecutive biopsies composed the study materials. 45 were excluded due to significant artifacts or small analysis areas (<6mm2). 208 bone marrow biopsies from 43 patients were included in the analysis. The group included 26 maintenance, 12 relapsed, and 5 smoldering patients; The relapsed and maintenance patients received Bortezomib alone or in combination for a minimum of three cycles; smoldering patients received bortezomib as part of a phase 2 study at the weekly dose of 0.7mg/kg. All maintenance and relapsed, patients had previously received bone marrow transplant with a median 68 years of age 29 were male. Median baseline TV/HR was 32.9%for maintenance 29.8% for relapse and 33.1% smoldering groups. A median increment of TV/RH (17%) was observed after Bortezomib treatment in all groups of patients (p<0.0001). Conclusion: Analysis of bone associated changes after Bortezomib exposure in patients with multiple myeloma by Scan Scope XT demonstrate a post treatment overall gain in bone formation. Monitoring bone indices in patients with multiple myeloma with PRIA may provide a valid tool to assess treatment associated bone effect. Disclosures: No relevant conflicts of interest to declare.

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Role of Immunohistochemistry and Quantitative PCR in Detection of B-Cell Lymphoma Infiltration in Bone Marrow

Advanced Science Letters ◽

10.1166/asl.2018.12695 ◽

2018 ◽

Vol 24 (8) ◽

pp. 6232-6237

Author(s):

Agnes Stephanie Harahap ◽

Endang S. R Hardjolukito ◽

Elly Yanah Arwanih ◽

Naivedh Bhat ◽

Maria Francisca Ham

Keyword(s):

Bone Marrow ◽

B Cell ◽

Quantitative Pcr ◽

Bone Marrow Biopsy ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Diagnostic Techniques ◽

P Value ◽

Fresh Tissue ◽

Bone Marrow Biopsies

Bone marrow infiltration of malignant lymphoma is essential for staging and prognosis, and could be detected by trephine biopsy. Using routine Hematoxylin and Eosin (HE) staining alone cannot accurately identify infiltration of lymphoma in bone marrow, therefore alternative techniques may be needed. Fifty-three bone marrow biopsies of B-cell lymphoma cases with age ranged from 29 to 74 year-old were included. Lengths of the bone marrow samples were measured and sent for routine HE and immunohistochemistry (IHC) staining. Results were categorized into 3 groups; positive, negative and equivocal. Twenty-three (43%) cases were eligible for quantitative PCR (qPCR) and monoclonal status was determined, based on the expression of kappa and lambda light chains. Bone marrow biopsies of varying lengths (range; 3 to 20 mm) were analyzed. There were no significant differences between patient age and RNA result (p value 0.095) or bone marrow biopsy length and RNA result (p value 0.835). In 18 of 23 cases (78%), the IHC results in concordance with HE result. There were 5 cases showed definitive qPCR results. One case showed equivocal morphology by HE staining but had negative IHC result. Another case showed positive lymphoma infiltration by HE staining but equivocal IHC result. Both cases showed monoclonal qPCR status. There was also another case with both negative HE and IHC staining showed consistent polyclonal qPCR result, as expected. These findings provide evidence that HE and IHC staining alone were not accurate enough to confirm the infiltration of lymphoma in bone marrow. Combinations of multiple diagnostic techniques are necessary to detect minimal infiltration of B-cell lymphoma in bone marrow biopsy. To acquire reliable qPCR results, the use of fresh tissue as resource of sample is recommended.

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Increased expression of cyclin-D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

American Journal of Hematology ◽

10.1002/ajh.23223 ◽

2012 ◽

Vol 87 (7) ◽

pp. 734-736 ◽

Cited By ~ 5

Author(s):

Anna Tasidou ◽

Maria Roussou ◽

Evangelos Terpos ◽

Efstathios Kastritis ◽

Maria Gkotzamanidou ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Cyclin D1 ◽

Novel Agents ◽

Bone Marrow Biopsies

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Raised ?2-Microglobulin as a Surrogate Marker in Non-Secretory Multiple Myeloma

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v16i1.31146 ◽

2017 ◽

Vol 16 (1) ◽

pp. 142-145

Author(s):

Bimal K Agrawal ◽

Anshul Sehgal ◽

Vikas Deswal ◽

Prem Singh ◽

Usha Agrawal

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Rare Case ◽

Plasma Cells ◽

Medical Science ◽

Protein A ◽

Surrogate Marker ◽

M Protein ◽

Review Of Literature ◽

Lytic Lesions

Multiple myeloma is a neoplasm of plasma cells in the bone marrow. It is characterised by lytic lesions in the bones, marrow plasmacytosis and presence of M protein in serum and/or urine. Serum ?2 microglobulin is also raised and can be used for classification and prognostication of the disease. In the absence of M protein, the disease is known as non-secretory myeloma. It is proposed that raised ?2 microglobulin can be used for diagnosis and therapeutic guidance in the absence of M protein. A rare case of nonsecretory myeloma with neurocognitive impairment along with review of literature is being presented. The patient had multiple lytic lesions in bones with marked increase in plasma cells in bone marrow. M protein was not detectable in serum or urine but serum ?2 microglobulin was much elevated.Bangladesh Journal of Medical Science Vol.16(1) 2017 p.142-145

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Lack of Utility of CD20 Immunohistochemistry in Staging Bone Marrow Biopsies for Diffuse Large B-cell Lymphoma

Applied Immunohistochemistry & Molecular Morphology ◽

10.1097/pai.0b013e318184cd3f ◽

2009 ◽

Vol 17 (2) ◽

pp. 93-95 ◽

Cited By ~ 3

Author(s):

Daniel Baiyee ◽

Roger Warnke ◽

Yasodha Natkunam

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Bone Marrow Biopsies ◽

Large B Cell Lymphoma ◽

Large B Cell

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Clinical Relevance of Bone Marrow Biopsy in Staging and Follow-Up of Breast Cancer

Tumori Journal ◽

10.1177/030089168306900210 ◽

1983 ◽

Vol 69 (2) ◽

pp. 143-150 ◽

Cited By ~ 2

Author(s):

Giorgio Cruciani ◽

Gian Maria Fiorentini ◽

Giovanni Rosti ◽

Amelia Tienghi ◽

Daniele Bardella ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Bone Metastases ◽

Bone Marrow Biopsy ◽

Clinical Relevance ◽

Bone Biopsy ◽

Bone Marrow Biopsies ◽

Female Patients

Bone marrow biopsies by Jamshidi needle were performed in 106 breast cancer female patients. Sixty-four of them were in follow-up after mastectomy, and neoplastic involvement of marrow was found in 21 patients (32.8%). Among the 42 women undergoing staging before mastectomy, the incidence of marrow involvement was 11.9% (5 women, all with radiographic positivity). Of the 37 women, either in follow-up or in the staging phase, with bone metastases detected by roentgenographic and isotopic examination, the bone biopsy was positive in 23 (62.1%), and 7 histologically had micrometastases. Three women, without any radiographic or isotopic sign of metastases, had positive biopsies. A good correlation was found between the hydroxyproline:creatinine ratio and neoplastic involvement of bone marrow.

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The CXCR4–CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms20194740 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4740 ◽

Cited By ~ 5

Author(s):

Katrin Pansy ◽

Julia Feichtinger ◽

Barbara Ehall ◽

Barbara Uhl ◽

Miriam Sedej ◽

...

Keyword(s):

Bone Marrow ◽

Cell Lines ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

Cxcr4 Expression ◽

Lymphoma Cell ◽

Bone Marrow Biopsies ◽

Cxcr4 Antagonists ◽

Apoptotic Effects

In tumor cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls, which was associated with poor clinical outcome. In corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Additionally, we investigated the effects of three CXCR4 antagonists in vitro. Therefore, we used AMD3100 (Plerixafor), AMD070 (Mavorixafor), and WKI, the niacin derivative of AMD070, which we synthesized. WK1 demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of pro-apoptotic genes of the BCL2-family in CXCR4-positive lymphoma cell lines. Finally, WK1 treatment resulted in the reduced expression of JNK-, ERK1/2- and NF-κB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas.

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Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features

Case Reports in Hematology ◽

10.1155/2018/9052314 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Abdullah M. Khan ◽

Jameel Muzaffar ◽

Hermant Murthy ◽

John R. Wingard ◽

Jan S. Moreb

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Bone Marrow Biopsy ◽

Lymphoblastic Leukemia ◽

Second Primary ◽

Cell Transplant ◽

Second Primary Malignancy ◽

Primary Malignancy ◽

Prognostic Features

Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20–84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved.

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