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An Unprecedented Case of AL and Apolipoprotein A-IV Renal Amyloidosis
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.
Background
Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.
Case Presentation
A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.
Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.
Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.
Discussion
While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.
Conclusions
Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.
Treatment Patterns and Outcomes of Older (Age ≥ 80) Veterans With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
Background
Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.
Methods
We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.
Results
We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.
Conclusions
Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.
Background
Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.
Methods
We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.
Results
We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.
Conclusions
Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.
Background
Over one-third of newly diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) cases are in people age ≥75. Although a potentially curable malignancy, older adults have a comparatively lower survival rate. This may be due to multiple factors including suboptimal management. In one study, up to 23% of patients age ≥80 did not receive any therapy for DLBCL. This age-related survival disparity is potentially magnified in patients who reside in rural areas. As there is no standard of care for this population, we speculate that there is wide variation in treatment practices which may influence outcomes. The purpose of this study is to describe treatment patterns and outcomes in in veterans age ≥80 with DLBCL by area of residence.
Methods
We conducted a retrospective study of veterans age ≥80 newly diagnosed with Stage II-IV DLBCL between 2006-2023 using the Veterans Affairs (VA) Cancer Registry System (VACRS). Patient, disease, and treatment variables were extracted from the VA Corporate Data Warehouse (CDW) and via chart review. Variables were compared amongst Veterans residing at urban vs. rural addresses.
Results
We evaluated a total of 181 Veterans. Most veterans resided in an urban area (60.2%). At least 18.8% of veterans failed to start lymphoma-directed therapy, but only 6.6% of veterans were not explicitly offered treatment per documentation. In total, 68.5% of veterans were offered a curative treatment regimen by their provider; curative treatment was more likely to be offered to urban patients (68.8% vs 61.5%, p=0.86). Pre-phase steroids and geriatric assessments prior to treatment were severely underutilized (2.8% and 0.6%). More urban veterans started treatment (75.2% vs 65.4%, p=0.38) and 40.9% started an anthracyclinecontaining regimen. Only 27.6% of veterans completed 6 total cycles of treatment. Only 37.6% of veterans achieved a complete response at end of treatment, although response was not reported in 46.4% of patients.
Conclusions
Most elderly veterans with DLBCL are being offered and started on a curative treatment regimen; however, most do not complete a full course of treatment. Although not statistically significant, more urban veterans were offered a curative regimen and received treatment. Wider adoption of pre-phase steroids and geriatric assessments could improve response outcomes.
Close to Me: Cost Savings Analysis and Improving Veteran Access
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.
BACKGROUND
While the MISSION Act for community care has increased Veteran access to specialty services, this has caused considerable fragmentation of care and financial cost to U.S. taxpayers. The VA Salt Lake City Health Care System (VA SLCHCS) referral area spans 125,000 square miles, one of the largest geographic regions in the VA health care system. Numerous VA Community- Based Outpatient Clinics (CBOCs) have been established in central and southern Utah, eastern Nevada, and southern Idaho; however, these clinics do not currently provide specialty services.
DISCUSSION
In conjunction with the National Oncology Program’s Close to Me project team, we conducted a cost analysis to determine financial feasibility of providing low-risk oncology parenteral therapies at rural CBOCs. Based on FY22 DO Paid Claim PowerBI and Pyramid Analytics Reports, VA SLCHCS paid claims for Community Care Hematology/Oncology community services in excess of $5.7 million for 380 unique Veterans (approximately $15,060 per unique Veteran). Comparatively, Veterans received high quality oncology care through VA SLCHCS with an estimated average cost of care of $5,424 per unique Veteran. Cost of parenteral therapies was estimated via review of Community Care Paid Claims Reports for individual drug claim costs (based on Jcode), VA drug pricing data from the VA National Acquisition Center Catalog, and drug unit claims data. The unit price of VA-care and community care costs were calculated and drug cost at the VA versus non- VA was compared. By retaining or re-establishing Hematology/Oncology Veteran care within VA, we estimate cost savings of approximately $9,636 per unique Veteran.
CONCLUSIONS
By re-establishing oncology care within VA SLCHCS the facility could net a substantial cost savings while simultaneously making Veterans lives easier, reduce need for transportation to/from the main SLC VA site, decrease costs due to VA pricing contracts, lessen Veteran out-of-pocket costs, improve care coordination through use of one electronic medical record, and maintain Veteran care within VA SLCHCS. Additionally, VA SLCHCS oncology will help lead the effort to launch a system within the CBOC’s to deliver high-cost parental therapies that could benefit other medical specialties such as gastroenterology, dermatology, and rheumatology.