scholarly journals Radioimmunodetection of amyloid deposits in patients with AL amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2241-2244 ◽  
Author(s):  
Jonathan S. Wall ◽  
Stephen J. Kennel ◽  
Alan C. Stuckey ◽  
Misty J. Long ◽  
David W. Townsend ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Al Amyloidosis ◽  
Disease Extent ◽  
Passive Immunotherapy ◽  
Negative Results ◽  
Biopsy Specimens ◽  
Amyloid Deposits ◽  
Pet Ct ◽  
Pet Ct Scan ◽  
Murine Igg1

Abstract Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that 124I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody. This trial was registered at www.clinicaltrials.gov as NCT00807872.

scholarly journals Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

2020 ◽  
Vol 144 (8) ◽  
pp. 967-973 ◽  
Author(s):  
Sara Javidiparsijani ◽  
Maria M. Picken
Keyword(s):  
Bone Marrow ◽  
Spatial Distribution ◽  
Plasma Cells ◽  
Treatment Options ◽  
Clinical Information ◽  
Al Amyloidosis ◽  
Significant Heterogeneity ◽  
Amyloid A ◽  
Amyloid Deposits ◽  
Amyloid Light Chain

Context.— Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options. Objective.— To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance. Design.— We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information. Results.— In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as amyloid light chain (AL) amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, amyloid transthyretin (ATTR), and amyloid A (AA). The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ. Conclusions.— This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.

Assessment of the role of 18F-FDG PET CT in detection of bone marrow infiltration in comparison to the Bone Marrow Aspirate in Lymphoma patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Madonna Adel Mikhail Ghaly ◽  
Aida Mohamed El Shibiny ◽  
Susan Adil Ali Abdul Rahim
Keyword(s):  
Bone Marrow ◽  
Ct Scan ◽  
Fdg Pet ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Bone Marrow Infiltration ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Pet Ct Scan

Abstract Background 18-F-2-Deoxy-D-Glucose Positron Emission Tomography [FDG-PET], combined with multidetector helical Computed Tomography [PET/CT] has emerged as a one of the most important prognostic tools for lymphoma management. Previous studies have indicated that PET/CT is a convenient method for bone marrow assessment in patients with lymphoma. A blind Bone Marrow Biopsy [BMB] has been traditionally used as the golden standard in marrow evaluation despite its invasiveness. Objective is to compare the results of PET/CT with BMB regarding bone marrow infiltration [BMI] in patients with Hodgkin's Lymphoma [HL] and Non-Hodgkin's Lymphoma [NHL] and to characterize the visual bone marrow FDG uptake pattern by PET-CT Methods A cross sectional study including 27 cases of Lymphoma, conducted at Ain Shams University hospitals, the patients were investigated using PET-CT scan and BMB ,the period was between December 2018 till the end of May 2019. Results Our study included 27 histologically proved Lymphoma patients, 14 (51.9%) were males and 13 (48.1%) were females, with age ranging from 17 to 69 years (mean 45 years). Among the total cases, 17 (63%) patients had NHL, while 10 (37%) patients had HL. All the patients were evaluated at first by BMB (taken from the dorsal portion of the iliac crest) for initial staging, then the patients underwent PET/CT scan. The study revealed 12 patients (44.4%) had BMI detected by PET/CT imaging; however, only 7 patients (25.9%) were detected by BMB. BMB and 18F-FDG PET/CT scans were concordant for BMI detection in 22 patients (81.5%): positive concordance in 7 patients and negative in 15. Of the 5 discordant cases, four had a focal marrow intense FDG uptake detected by PET/CT and were upstaged as their BMB results were false-negative, one patient had intense diffuse marrow uptake by PET/CT while its BMB was negative (revealed only hyper cellularity with mild dysplasia). The sensitivity, specificity, PPV, and NPV of PET for identifying BMI was 100%, 75%, 58.3%, 100% respectively with a diagnostic accuracy 81.5% with a (p value < 0.05). Conclusion 18F-FDG PET-CT imaging is more sensitive than bone marrow biopsy for bone marrow infiltration detection in Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma staging.

Utility of Bone Marrow Biopsy in the Staging of Diffuse Large B-Cell Lymphoma in the Era of PET-CT

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5637-5637
Author(s):  
Prakash Vishnu ◽  
Andrew Wingerson ◽  
David M Aboulafia
Keyword(s):  
Bone Marrow ◽  
Predictive Value ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Pre Treatment ◽  
Pet Ct Scan

Abstract BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). Recent advances in imaging, use of prognostic indices and molecular profiling has improved our ability to characterize disease and predict outcomes in DLBCL. About one-third of patients with DLBCL have bone marrow involvement at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered gold standard to detect such involvement. 18 F-fluro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (PET-CT), has become standard pre-treatment imaging in DLBCL and may be a non-invasive alternative to BMAB. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly-diagnosed DLBCL, but owing to a variety of reasons this is not yet a standard of practice. We investigated whether FDG uptake-based bone marrow assessment can replace BMAB in newly-diagnosed DLBCL. METHODS This study is a single institution retrospective medical records' review. All patients with newly-diagnosed DLBCL at Virginia Mason Medical Center between January 2003 to December 2013 who underwent pre-treatment PET-CT and BMAB were included. FDG-PET/CT images were visually assessed for bone marrow involvement in posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or coexistence of another lymphoma subtype and those with a non-diagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured. RESULTS 105 eligible patients were identified. The median age was 62 years (range, 24-88), 62 (59%) were male, 53 (50%) had elevated LDH and 17 (16%) had an ECOG performance status of >2. Thirteen (12%) patients had > 1 extra-nodal site of lymphoma involvement. R-IPI score was 0-1 in 39 (37%), 2 in 42 (40%), 3 in 20 (19%), and 4 in 4 (4%) patients. A total of 38 (36%) patients had bone marrow involvement established by either PET-CT (n=24, 19%), BMAB (n=14, 13%), or both (n=12, 11%). 12 of the 24 patients (50%) with positive PET-CT had marrow involvement by DLBCL, while only 2 of the 81 patients (2%) with negative PET/CT showed marrow involvement. BMAB upstaged 1 of the 53 (2%) stage I/II patients to stage IV. The sensitivity of PET-CT scan to detect marrow involvement by DLBCL was 86% while the specificity was 87%. The positive predictive value of PET-CT was only 50% while the negative predictive value was 98%. CONCLUSIONS In patients with newly diagnosed DLBCL, PET-CT is complementary to BMAB in detecting marrow involvement by lymphoma. Although PET-CT has a high negative predictive value for bone marrow involvement, it overestimates the number of cases with marrow involvement by lymphoma. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL, who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of marrow involvement identified by PET-CT compared to BMAB remains unknown. Disclosures No relevant conflicts of interest to declare.

scholarly journals Disseminated focal 18F-fluoro-deoxyglucose uptake upon granulocyte colony-stimulating factor therapy mimicking malignant bone infiltration: case report of a patient with very severe aplastic anemia

2020 ◽  
Vol 11 ◽  
pp. 204062072097761
Author(s):  
Lena Horvath ◽  
Andreas Seeber ◽  
Christian Uprimny ◽  
Dominik Wolf ◽  
David Nachbaur ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ct Scan ◽  
Aplastic Anemia ◽  
Fdg Pet ◽  
Mediastinal Mass ◽  
Pet Ct ◽  
Bone Infiltration ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Pet Ct Scan

Combined 18F-fluoro-deoxyglucose ([18F]FDG) positron emission tomography and computed tomography ([18F]FDG-PET/CT) is increasingly used for the diagnostic and therapeutic management of hematologic and non-hematologic malignancies. Here, we describe a unique case of a patient presenting with very severe aplastic anemia and a mediastinal mass showing disseminated hypermetabolic lesions of the bones after receiving granulocyte colony-stimulating factor (G-CSF), highly suspicious for disseminated metastatic lesions. A 71-year-old patient presented with a 3 week history of dyspnea and fatigue. Blood tests showed severe pancytopenia and iliac crest bone marrow biopsy revealed an extensively hypoplastic bone marrow. Diagnostic work-up by histology, conventional cytogenetics and flow cytometry confirmed the diagnosis of very severe aplastic anemia. Besides blood transfusions, the patient was treated with G-CSF. Furthermore, computed tomography revealed a suspect mass in the anterior mediastinum, presenting with moderate glucose metabolism in the subsequent [18F]FDG-PET/CT scan. In addition, multiple disseminated and highly metabolic bone lesions of primarily the ribs were detected, suspicious of malignant bone infiltration. Since physiologic bone marrow activation by G-CSF-stimulation could not be ruled out, G-CSF therapy was interrupted to repeat the PET/CT scan 10 days later. On the second [18F]FDG-PET/CT the moderately hypermetabolic mediastinal mass persisted. However, the initially FDG-avid bone lesions almost completely resolved, rendering the diagnosis of G-CSF-induced bone marrow hypermetabolism very likely without the need for further invasive diagnostic procedures. The mediastinal mass was thereafter histologically verified as thymoma. Interpretation of [18F]FDG-PET/CT in patients with aplastic anemia may be complicated by the frequent therapeutic use of G-CSF. With G-CSF, islets of residual bone marrow activity can be visualized on [18F]FDG-PET/CT images that might be misinterpreted as malignant bone infiltration. Repeating PET/CT scan after G-CSF discontinuation can prevent unnecessary invasive diagnostic procedures in these patients.

Bone marrow trephine biopsy in Hodgkin's lymphoma. Comparison with PET–CT scan in 65 patients

2018 ◽  
Vol 150 (3) ◽  
pp. 104-106
Author(s):  
Sunil Lakhwani ◽  
Dolores Cabello-García ◽  
Ana Allende-Riera ◽  
Carlos Cárdenas-Negro ◽  
José María Raya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ct Scan ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Trephine Biopsy ◽  
Bone Marrow Trephine ◽  
Bone Marrow Trephine Biopsy ◽  
Pet Ct ◽  
Pet Ct Scan

scholarly journals Autologous bone marrow mononuclear cell transplantation in patients with chronic traumatic brain injury- a clinical study

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Alok K. Sharma ◽  
Hemangi M. Sane ◽  
Pooja P. Kulkarni ◽  
Nandini Gokulchandran ◽  
Hema Biju ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Bone Marrow ◽  
Adverse Events ◽  
Cell Transplantation ◽  
Autologous Bone Marrow ◽  
Pet Ct ◽  
Autologous Bone ◽  
Time Since Injury ◽  
Pet Ct Scan

Abstract Background Chronic Traumatic Brain Injury (TBI) is one of the common causes of longterm disability worldwide. Cell transplantation has gained attention as a prospective therapeutic option for neurotraumatic disorders like TBI. The postulated mechanism of cell transplantation which includes angiogenesis, axonal regeneration, neurogenesis and synaptic remodeling, may tackle the pathology of chronic TBI and improve overall functioning. Methods To study the effects of cell transplantation, 50 patients with chronic TBI were enrolled in an open label non-randomized study. The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation. Mean follow up duration was 22 months. Fifteen patients underwent second dose of cell transplantation, 6 months after their first intervention. Percentage analysis was performed to analyze the symptomatic improvements in the patients. Functional independence measure (FIM) was used as an outcome measure to evaluate the functional changes in the patients. Statistical tests were applied on the pre-intervention and post-intervention scores for determining the significance. Comparative Positron Emission Tomography- computed tomography (PET CT) scans were performed in 10 patients to monitor the effect of intervention on brain function. Factors such as age, multiple doses, time since injury and severity of injury were also analyzed to determine their effect on the outcome of cell transplantation. Adverse events were monitored throughout the follow up period. Results Overall 92% patients showed improvements in symptoms such as sitting and standing balance, voluntary control, memory, oromotor skills lower limb activities, ambulation, trunk & upper limb activity, speech, posture, communication, psychological status, cognition, attention and concentration, muscle tone, coordination, activities of daily living. A statistically significant (at p ≤ 0.05 with p-value 0) improvement was observed in the scores of FIM after intervention on the Wilcoxon signed rank test. Better outcome of the intervention was found in patients with mild TBI, age less than 18 years and time since injury less than 5 years. Ten patients who underwent a repeat PET CT scan brain showed improved brain metabolism in areas which correlated to the symptomatic changes. Two patients had an episode of seizures which was managed with medication. They both had an abnormal EEG before the intervention and 1 of them had previous history and was on antiepileptics. No other major adverse events were recorded. Conclusion This study demonstrates the safety and efficacy of cell transplantation in chronic TBI on long term follow up. Early intervention in younger age group of patients with mild TBI showed the best outcome in this study. In combination with neurorehabilitation, cell transplantation can enhance functional recovery and improve quality of life of patients with chronic TBI. PET CT scan brain should be explored as a monitoring tool to study the efficacy of intervention.

Macroglossia – Not Always AL Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5007-5007 ◽  
Author(s):  
Andrew J Cowan ◽  
Martha Skinner ◽  
J. Mark Sloan ◽  
John L Berk ◽  
Carl J O'Hara ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Amyloid Deposits ◽  
Immuno Electron Microscopy ◽  
Congo Red Staining

Abstract Abstract 5007 Introduction: Amyloidosis is characterized by extracellular deposition of abnormal insoluble fibrillar proteins. The two most frequent systemic amyloidoses are the light-chain (AL amyloidosis) and familial transthyretin (ATTR) forms. Clinical presentations often vary between the two types. Macroglossia is viewed as pathognomic of AL amyloidosis, and has not previously been described in patients with hereditary TTR amyloidosis. Here, we describe two cases of systemic amyloidosis with macroglossia in which immuno-electron microscopy diagnosed ATTR in one and AL in the other. Case Presentations: A 61 year old woman presented initially to her general internist with weight loss, difficulty swallowing, and tongue numbness. Her clinical exam revealed macroglossia and peripheral neuropathy. Tongue and axillary lymph node biopsies demonstrated amyloid deposits by Congo red staining. There was no evidence of renal, cardiac or other vital organ involvement. She had no evidence of a plasma cell dyscrasia with negative serum and urine immunofixation electrophoresis, normal serum free light chain concentration and ratio as well as polytypic plasma cells in the bone marrow. Immuno-electron microscopy using gold-labeled antibodies was performed on the tongue biopsy. The fibrils were immunoreactive with anti-TTR but not anti-kappa, anti-lambda, or anti-AA antibodies. DNA sequencing identified a known amyloidogenic T60A TTR mutation in exon 3 of chromosome 18, confirming the diagnosis of ATTR with amyloidotic polyneuropathy and macroglossia. The second case involved a 59 year old man with renal insufficiency. He complained of fatigue, weight loss, and tongue swelling. Physical examination was significant for macroglossia and submandibular gland enlargement. Tongue biopsy demonstrated amyloid deposits by Congo red staining. As in the previous case, markers of plasma cell dyscrasia with clonal plasma cells in the bone marrow, blood, and urine were absent. Immuno-electron microscopy of the tongue biopsy documented antibody reactivity to lambda light chain and not TTR, kappa light chain or AA proteins, confirming the diagnosis of AL amyloidosis. He subsequently underwent treatment with high dose intravenous melphalan followed by stem cell transplantation achieving a good clinical response sustained for 2 years to date. Discussion: While macroglossia is thought to be pathognomonic of AL amyloidosis, we report a case of macroglossia with fibrillar ATTR amyloid deposits diagnosed by immuno-electron microscopy. This is contrasted with a clinical presentation consistent with AL in which routine laboratory testing failed to identify evidence of a plasma cell dyscrasia. In both cases, electron microscopy demonstrated immunoreactivity for the fibrils of a single pathogenic protein. The first case was confirmed by DNA sequencing, and the second had a typical response to anti-plasma cell chemotherapy, in spite of the lack of identifiable markers of disease. Disclosures: No relevant conflicts of interest to declare.

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