Transplantation for amyloidosis

Gertz, Morie A.; Lacy, Martha Q.; Dispenzieri, Angela; Hayman, Suzanne R.; Kumar, Shaji

doi:10.1097/cco.0b013e32801494c6

Cited by 81 publications

(60 citation statements)

References 29 publications

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“…Standard therapy consists of melphalan plus dexamethasone; selected patients with limited organ involvement are considered for high-dose melphalan with ASCT. 63,64 Thalidomide has shown limited activity and increased toxicity in amyloidosis patients compared to MM. [65][66][67] The more favorable toxicity profile of lenalidomide has led to the investigation of the drug in AL amyloidosis.…”

Section: Lenalidomide In Systemic Light Chain Amyloidosismentioning

confidence: 99%

Treatment of plasma cell dyscrasias with lenalidomide

Dimopoulos

Rajkumar

2008

Leukemia

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Lenalidomide is an immunomodulatory drug, structurally related to thalidomide, with pleiotropic activity including antiangiogenic and antineoplastic properties. It is the product of advances in our understanding of the biology of myeloma cells, their interactions with the microenvironment and of the underlying molecular pathways. In preclinical and clinical studies, lenalidomide was more potent and less toxic than thalidomide. Subsequent phase II and III studies confirmed the activity of lenalidomide either as a single agent or in combination with dexamethasone in relapsed or refractory myeloma patients, whereas combinations with chemotherapy induce high response rates and durable remissions. Lenalidomide has been used successfully as an upfront treatment either with high or low dose dexamethasone or with melphalan and prednisone, resulting in high overall response and complete response rates and excellent 1-year survival. Lenalidomide causes less neuropathy than thalidomide; however, the risk of thromboembolism is high, especially in patients treated with lenalidomide and steroids. In this review, we summarize the mechanisms of action, toxicity and clinical activity, and the current role of lenalidomide in patients with multiple myeloma or other related plasma cell disorders.

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Section: Lenalidomide In Systemic Light Chain Amyloidosismentioning

confidence: 99%

Treatment of plasma cell dyscrasias with lenalidomide

Dimopoulos

Rajkumar

2008

Leukemia

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“…Although autologous peripheral blood stem-cell transplantation (SCT) can improve the outcome of selected patients, a majority of patients with amyloidosis are ineligible for this approach because of significant organ involvement. [4][5][6][7] Alternative treatments such as melphalan and dexamethasone with or with out novel drugs like lenalidomide and bortezomib seem promising. [8][9][10][11] Hence, it is important to develop risk classification systems that will allow more accurate assessment of prognosis and potentially help select the optimal therapy.…”

Section: Introductionmentioning

confidence: 99%

Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements

Kumar

Dispenzieri

Lacy

et al. 2012

JCO

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A B S T R A C T PurposeCardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification. Patients and MethodsWe developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials. ResultsWe examined the prognostic value of plasma cell-related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and ␤ 2 microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff Ն 18 mg/dL, cTnT Ն 0.025 ng/mL, and NT-ProBNP Ն 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P Ͻ .001). This classification system was validated in the other datasets. ConclusionIncorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis. J Clin

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“…[1][2][3] High-dose melphalan with autologous stem cell transplant (HDM/SCT) is an effective treatment with high complete hematologic response rates (CR) and is capable of producing durable remissions and prolonged overall survival. [4][5][6] Only selected patients are eligible to receive HDM/SCT, and treatment-related mortality is in the range of 5-15%. More effective and widely applicable treatment modalities in AL amyloidosis are, therefore, needed.…”

Section: Introductionmentioning

confidence: 99%

Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial

Sanchorawala

Sloan

et al. 2012

Haematologica

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2/day for four days, lenalidomide 10 mg/day for 21 days and dexamethasone 20-40 mg once a week every 28 days for a total of 12 cycles. Sixteen subjects were enrolled of whom 14 completed at least 3 cycles and were evaluable for response. Grade 3/4 toxicities were experienced by 88% (n=14), the most common being myelosuppression (n=7). Dose reductions occurred in 85% (n=12 of 14) of subjects. Hematologic partial and complete responses were achieved by 43% (n=6 of 14) and 7% (n=1 of 14), respectively. The median overall survival has not been reached and median progression-free survival is 24 months. In conclusion, this combination is associated with significant myelosuppression leading to dose modifications and producing minor hematologic responses in AL amyloidosis. http://clinicaltrials.gov/ct2/show/NCT00679367 ABSTRACT ARTICLES Amyloidosis

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Transplantation for amyloidosis

Abstract: Partial response rates and complete response rates are prognosticators of survival for patients with amyloidosis. These rates are much higher for patients who receive high-dose therapy and transplantation.

Cited by 81 publications

References 29 publications

Treatment of plasma cell dyscrasias with lenalidomide

Treatment of plasma cell dyscrasias with lenalidomide

Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements

Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial

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