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Morie A Gertz - One of the best experts on this subject based on the ideXlab platform.

  • Immunoglobulin Light Chain amyloidosis diagnosis and treatment algorithm 2021
    Blood Cancer Journal, 2021
    Co-Authors: Hasib M Sidiqi, Morie A Gertz
    Abstract:

    Immunoglobulin Light Chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for Light Chain amyloidosis. Overlooking the diagnosis of Light Chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.

  • Immunoglobulin Light Chain amyloidosis 2020 update on diagnosis prognosis and treatment
    American Journal of Hematology, 2020
    Co-Authors: Morie A Gertz
    Abstract:

    DISEASE OVERVIEW Immunoglobulin Light Chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of Immunoglobulin Light or heavy Chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy undetermined significance (MGUS)." DIAGNOSIS Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of Immunoglobulin Light Chains is mandatory. The gold standard is laser capture mass spectroscopy. PROGNOSIS N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponin T, and difference between involved and uninvolved Immunoglobulin free Light Chain (FLC) values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. THERAPY All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90 mmHg, troponin T < 0.06 ng/mL and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered cyclophosphamide-bortezomib-dexamethasone or daratumumab-containing regimens as it appears to be highly active in AL amyloidosis. FUTURE CHALLENGES Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure.

  • comparison of different techniques to identify cardiac involvement in Immunoglobulin Light Chain al amyloidosis
    Blood Advances, 2018
    Co-Authors: Mohammed A Aljama, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Morie A Gertz, Hasib M Sidiqi, Eli Muchtar, Amie Fonder, Suzanne R Hayman
    Abstract:

    We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic Immunoglobulin Light Chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP

  • systemic Immunoglobulin Light Chain amyloidosis
    Nature Reviews Disease Primers, 2018
    Co-Authors: Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Angela Dispenzieri, Stefan Schonland, Philip N Hawkins, Morie A Gertz
    Abstract:

    Systemic Immunoglobulin Light Chain amyloidosis is a protein misfolding disease caused by the conversion of Immunoglobulin Light Chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid Light Chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.

  • Immunoglobulin Light Chain amyloidosis diagnosis and treatment algorithm 2018
    Blood Cancer Journal, 2018
    Co-Authors: Morie A Gertz
    Abstract:

    Immunoglobulin Light Chain amyloidosis (AL) should be considered in any patient that presents to a cancer care provider with nephrotic range proteinuria, heart failure with preserved ejection fraction, non-diabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for Light Chain amyloidosis. Overlooking the diagnosis of Light Chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Algorithms will be provided on how to evaluate patients with suspected AL amyloid as well as how to manage patients referred from other medical specialties with biopsy-proven amyloid. An organized stepwise approach to the treatment of patients with Light Chain amyloidosis, including established and investigational therapies, will be reviewed.

Angela Dispenzieri - One of the best experts on this subject based on the ideXlab platform.

  • a study from the mayo clinic evaluated long term outcomes of kidney transplantation in patients with Immunoglobulin Light Chain amyloidosis
    Kidney International, 2021
    Co-Authors: Francis K Buadi, Angela Dispenzieri, Cihan Heybeli, Andrew Bentall, Jiqiu Wen, Mariam P Alexander, Fernando G Cosio, Patrick G Dean, David Dingli
    Abstract:

    Longer survival using modern therapies has increased the number of patients with Immunoglobulin Light-Chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with Immunoglobulin Light Chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (Light-Chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with Immunoglobulin Light-Chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.

  • comparison of different techniques to identify cardiac involvement in Immunoglobulin Light Chain al amyloidosis
    Blood Advances, 2018
    Co-Authors: Mohammed A Aljama, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Morie A Gertz, Hasib M Sidiqi, Eli Muchtar, Amie Fonder, Suzanne R Hayman
    Abstract:

    We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic Immunoglobulin Light Chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP

  • prognostic significance of stringent complete response after stem cell transplantation in Immunoglobulin Light Chain amyloidosis
    Biology of Blood and Marrow Transplantation, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, Rahma Warsame, Eli Muchtar, Wilson I Gonsalves
    Abstract:

    Abstract Hematologic response has emerged as a powerful prognostic factor for survival in patients with Immunoglobulin Light Chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.

  • systemic Immunoglobulin Light Chain amyloidosis
    Nature Reviews Disease Primers, 2018
    Co-Authors: Giampaolo Merlini, Giovanni Palladini, Vaishali Sanchorawala, Angela Dispenzieri, Stefan Schonland, Philip N Hawkins, Morie A Gertz
    Abstract:

    Systemic Immunoglobulin Light Chain amyloidosis is a protein misfolding disease caused by the conversion of Immunoglobulin Light Chains from their soluble functional states into highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid Light Chain production in the majority of patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.

  • plasma cell proliferative index predicts outcome in Immunoglobulin Light Chain amyloidosis treated with stem cell transplantation
    Haematologica, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, William G Morice, Michael Timm, Rahma Warsame, David Dingli
    Abstract:

    The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic Immunoglobulin Light Chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

Martha Q Lacy - One of the best experts on this subject based on the ideXlab platform.

  • comparison of different techniques to identify cardiac involvement in Immunoglobulin Light Chain al amyloidosis
    Blood Advances, 2018
    Co-Authors: Mohammed A Aljama, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Morie A Gertz, Hasib M Sidiqi, Eli Muchtar, Amie Fonder, Suzanne R Hayman
    Abstract:

    We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic Immunoglobulin Light Chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP

  • prognostic significance of stringent complete response after stem cell transplantation in Immunoglobulin Light Chain amyloidosis
    Biology of Blood and Marrow Transplantation, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, Rahma Warsame, Eli Muchtar, Wilson I Gonsalves
    Abstract:

    Abstract Hematologic response has emerged as a powerful prognostic factor for survival in patients with Immunoglobulin Light Chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.

  • plasma cell proliferative index predicts outcome in Immunoglobulin Light Chain amyloidosis treated with stem cell transplantation
    Haematologica, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, William G Morice, Michael Timm, Rahma Warsame, David Dingli
    Abstract:

    The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic Immunoglobulin Light Chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

  • presentation and outcomes of localized Immunoglobulin Light Chain amyloidosis the mayo clinic experience
    Mayo Clinic Proceedings, 2017
    Co-Authors: Taxiarchis Kourelis, Francis K Buadi, David Dingli, Martha Q Lacy, Morie A Gertz, Shaji Kumar, Robert A. Kyle, Prashant Kapoor, Wilson I Gonsalves, Rahma Warsame
    Abstract:

    Abstract Objective To describe treatment types, outcomes, and relapse patterns in patients with localized Immunoglobulin Light Chain amyloidosis (AL L ). Patients and Methods We included all patients with AL L seen at Mayo Clinic in Rochester, Minnesota, from January 1, 1968, through June 30, 2014. The diagnosis of AL L was predicated on the presence of a Congo red–positive biopsy specimen and negative serum and urine immunofixation. Treatment response categories were response, stability, and progression. Localized and systemic progressions were defined as progression of disease at the site of origin or appearance of clonal plasma cells in a bone marrow biopsy sample, respectively. Results Of 5551 patients with AL, 413 (7%) had AL L . The most common site involved was urothelial tissue (n=85, 21%), followed by the larynx (n=57, 14%). Coexisting autoimmune diseases were reported in 7% of patients (n=28). The most common first-line treatment was excision of the amyloid deposits (61%), followed by observation or supportive care (28%). When considering symptomatic patients only (n=284), 205 (72%) improved, 23 (8%) had stable disease, and 55 (19%) could not be evaluated for response. Ten-year survival was 78% and was not different from that of the general population. There were no systemic progressions, but 17% of patients (n=72) had localized progression. Conclusion Localized AL is associated with a relatively distinct pattern of organ involvement. The initial laboratory evaluation to exclude systemic disease could be limited to serum and urine immunofixation in most patients. Recurrence after first-line therapy is common, but long-term outcomes are excellent.

  • overuse of organ biopsies in Immunoglobulin Light Chain amyloidosis al the consequence of failure of early recognition
    Annals of Medicine, 2017
    Co-Authors: Eli Muchtar, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Angela Dispenzieri, Rahma Warsame, Prashant Kapoor, Wilson I Gonsalves, Taxiarchis Kourelis, Rajshekhar Chakraborty
    Abstract:

    AbstractIntroduction: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat aspiration and/or bone marrow (BM) biopsy, but at times organ biopsy is required.Methods: We studied 612 patients with systemic Immunoglobulin Light Chain amyloidosis to characterise the tissues used to establish the diagnosis.Results: The median number of tissue samples was 3. About 95% of BM biopsies were stained for CR, while 79% of patients had fat aspiration CR-stained. CR stain sensitivity was 69% in BM, 75% in fat aspiration and 89% for both sources combined. In comparison, CR sensitivity was 97–100% for heart, renal and liver biopsies. About 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive biopsy would have established the diagnosis. Predictors for the requirement for organ biopsy were male sex, limited organ involvement and lack of f...

Francis K Buadi - One of the best experts on this subject based on the ideXlab platform.

  • a study from the mayo clinic evaluated long term outcomes of kidney transplantation in patients with Immunoglobulin Light Chain amyloidosis
    Kidney International, 2021
    Co-Authors: Francis K Buadi, Angela Dispenzieri, Cihan Heybeli, Andrew Bentall, Jiqiu Wen, Mariam P Alexander, Fernando G Cosio, Patrick G Dean, David Dingli
    Abstract:

    Longer survival using modern therapies has increased the number of patients with Immunoglobulin Light-Chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with Immunoglobulin Light Chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (Light-Chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with Immunoglobulin Light-Chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.

  • comparison of different techniques to identify cardiac involvement in Immunoglobulin Light Chain al amyloidosis
    Blood Advances, 2018
    Co-Authors: Mohammed A Aljama, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Morie A Gertz, Hasib M Sidiqi, Eli Muchtar, Amie Fonder, Suzanne R Hayman
    Abstract:

    We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic Immunoglobulin Light Chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP

  • prognostic significance of stringent complete response after stem cell transplantation in Immunoglobulin Light Chain amyloidosis
    Biology of Blood and Marrow Transplantation, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, Rahma Warsame, Eli Muchtar, Wilson I Gonsalves
    Abstract:

    Abstract Hematologic response has emerged as a powerful prognostic factor for survival in patients with Immunoglobulin Light Chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.

  • plasma cell proliferative index predicts outcome in Immunoglobulin Light Chain amyloidosis treated with stem cell transplantation
    Haematologica, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, William G Morice, Michael Timm, Rahma Warsame, David Dingli
    Abstract:

    The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic Immunoglobulin Light Chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

  • presentation and outcomes of localized Immunoglobulin Light Chain amyloidosis the mayo clinic experience
    Mayo Clinic Proceedings, 2017
    Co-Authors: Taxiarchis Kourelis, Francis K Buadi, David Dingli, Martha Q Lacy, Morie A Gertz, Shaji Kumar, Robert A. Kyle, Prashant Kapoor, Wilson I Gonsalves, Rahma Warsame
    Abstract:

    Abstract Objective To describe treatment types, outcomes, and relapse patterns in patients with localized Immunoglobulin Light Chain amyloidosis (AL L ). Patients and Methods We included all patients with AL L seen at Mayo Clinic in Rochester, Minnesota, from January 1, 1968, through June 30, 2014. The diagnosis of AL L was predicated on the presence of a Congo red–positive biopsy specimen and negative serum and urine immunofixation. Treatment response categories were response, stability, and progression. Localized and systemic progressions were defined as progression of disease at the site of origin or appearance of clonal plasma cells in a bone marrow biopsy sample, respectively. Results Of 5551 patients with AL, 413 (7%) had AL L . The most common site involved was urothelial tissue (n=85, 21%), followed by the larynx (n=57, 14%). Coexisting autoimmune diseases were reported in 7% of patients (n=28). The most common first-line treatment was excision of the amyloid deposits (61%), followed by observation or supportive care (28%). When considering symptomatic patients only (n=284), 205 (72%) improved, 23 (8%) had stable disease, and 55 (19%) could not be evaluated for response. Ten-year survival was 78% and was not different from that of the general population. There were no systemic progressions, but 17% of patients (n=72) had localized progression. Conclusion Localized AL is associated with a relatively distinct pattern of organ involvement. The initial laboratory evaluation to exclude systemic disease could be limited to serum and urine immunofixation in most patients. Recurrence after first-line therapy is common, but long-term outcomes are excellent.

David Dingli - One of the best experts on this subject based on the ideXlab platform.

  • a study from the mayo clinic evaluated long term outcomes of kidney transplantation in patients with Immunoglobulin Light Chain amyloidosis
    Kidney International, 2021
    Co-Authors: Francis K Buadi, Angela Dispenzieri, Cihan Heybeli, Andrew Bentall, Jiqiu Wen, Mariam P Alexander, Fernando G Cosio, Patrick G Dean, David Dingli
    Abstract:

    Longer survival using modern therapies has increased the number of patients with Immunoglobulin Light-Chain amyloidosis receiving kidney transplantation. We evaluated 60 patients with Immunoglobulin Light Chain amyloidosis who underwent kidney transplantation based on their hematologic response for outcomes of death, graft failure, and complications. Patient hematologic responses (Light-Chain in blood or urine) prior to kidney transplantation were three patients had no response, five had a partial response, six had a very good partial response, 37 had a complete response, and nine were treatment-naive patients (never treated for this disorder). After transplantation, seven of nine treatment-naive patients achieved a complete response. The median follow-up for the entire transplant cohort was 61 months. The estimated median overall survival from the time of kidney transplantation was 123 months for the entire group. Median overall survival was not reached for the very good partial response plus complete response groups, it was 47 months for no response plus partial response groups, and 117 months for the treatment-naive group (all significantly different). Median overall survival of very good partial response was 81 months, while the median was not reached in the complete response group (no significant difference). The time to amyloid recurrence was significantly longer in complete response compared to very good partial response (median 181 vs 81 months). Death-censored graft survival at one- and five-years was 98.3%, and 95.8%, respectively for all groups. Of the 60 patients, three had allograft failure, 19 died with a functioning graft, and 13 had an amyloid recurrence. Thus, outcomes after kidney transplant in patients with Immunoglobulin Light-Chain amyloidosis seem acceptable if a very good partial response or complete response is achieved either before or after transplantation.

  • comparison of different techniques to identify cardiac involvement in Immunoglobulin Light Chain al amyloidosis
    Blood Advances, 2018
    Co-Authors: Mohammed A Aljama, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Morie A Gertz, Hasib M Sidiqi, Eli Muchtar, Amie Fonder, Suzanne R Hayman
    Abstract:

    We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic Immunoglobulin Light Chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (>300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP

  • prognostic significance of stringent complete response after stem cell transplantation in Immunoglobulin Light Chain amyloidosis
    Biology of Blood and Marrow Transplantation, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, David Dingli, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, Rahma Warsame, Eli Muchtar, Wilson I Gonsalves
    Abstract:

    Abstract Hematologic response has emerged as a powerful prognostic factor for survival in patients with Immunoglobulin Light Chain (AL) amyloidosis. Patients achieving a complete response (CR), based on serum and urine analysis, survive longest. However, data regarding the impact of bone marrow features post-therapy on response and survival are limited. We evaluated the impact of achieving a stringent CR (sCR), defined as undetectable bone marrow clonal plasma cells by flow cytometry, in patients with AL amyloidosis receiving an autologous stem cell transplant. A total of 573 consecutive patients transplanted for AL amyloidosis at the Mayo Clinic between April 2002 and August 2016 were included in the analysis. Of 540 patients in whom response was assessable, 220 patients (41%) achieved a CR, of whom 212 (96%) had a bone marrow biopsy at time of response assessment and were further analyzed for determination of sCR; 166 patients (78%) with a CR achieved an sCR, representing 31% of the whole cohort. Patients achieving a CR had a higher median percentage of bone marrow plasma cells (10% for CR versus 6% for sCR, P = .03), more patients with bone marrow plasma cells ≥ 10% (50% for CR versus 33% for sCR, P = .04), and were less likely to receive chemotherapy before transplantation (30% for CR versus 49% for sCR, P = .03) compared with those achieving sCR. Median overall survival for all patients achieving a CR was 175 months and was not statistically different between those achieving an sCR compared with those achieving a CR only (median not reached for sCR versus 175 months for CR, P = .65). Progression-free survival, however, was significantly shorter in patients failing to achieve an sCR (151 months for sCR versus 72 months for CR, P = .0003). Bone marrow examination post-transplant in AL amyloidosis is important and identifies patients who fail to achieve an sCR and progress earlier.

  • plasma cell proliferative index predicts outcome in Immunoglobulin Light Chain amyloidosis treated with stem cell transplantation
    Haematologica, 2018
    Co-Authors: Hasib M Sidiqi, Francis K Buadi, Martha Q Lacy, Angela Dispenzieri, Mohammed A Aljama, Dragan Jevremovic, William G Morice, Michael Timm, Rahma Warsame, David Dingli
    Abstract:

    The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic Immunoglobulin Light Chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

  • presentation and outcomes of localized Immunoglobulin Light Chain amyloidosis the mayo clinic experience
    Mayo Clinic Proceedings, 2017
    Co-Authors: Taxiarchis Kourelis, Francis K Buadi, David Dingli, Martha Q Lacy, Morie A Gertz, Shaji Kumar, Robert A. Kyle, Prashant Kapoor, Wilson I Gonsalves, Rahma Warsame
    Abstract:

    Abstract Objective To describe treatment types, outcomes, and relapse patterns in patients with localized Immunoglobulin Light Chain amyloidosis (AL L ). Patients and Methods We included all patients with AL L seen at Mayo Clinic in Rochester, Minnesota, from January 1, 1968, through June 30, 2014. The diagnosis of AL L was predicated on the presence of a Congo red–positive biopsy specimen and negative serum and urine immunofixation. Treatment response categories were response, stability, and progression. Localized and systemic progressions were defined as progression of disease at the site of origin or appearance of clonal plasma cells in a bone marrow biopsy sample, respectively. Results Of 5551 patients with AL, 413 (7%) had AL L . The most common site involved was urothelial tissue (n=85, 21%), followed by the larynx (n=57, 14%). Coexisting autoimmune diseases were reported in 7% of patients (n=28). The most common first-line treatment was excision of the amyloid deposits (61%), followed by observation or supportive care (28%). When considering symptomatic patients only (n=284), 205 (72%) improved, 23 (8%) had stable disease, and 55 (19%) could not be evaluated for response. Ten-year survival was 78% and was not different from that of the general population. There were no systemic progressions, but 17% of patients (n=72) had localized progression. Conclusion Localized AL is associated with a relatively distinct pattern of organ involvement. The initial laboratory evaluation to exclude systemic disease could be limited to serum and urine immunofixation in most patients. Recurrence after first-line therapy is common, but long-term outcomes are excellent.