Chapter 39 Immunoglobulin Light-Chain Amyloidosis (Primary Amyloidosis)
Table 39-1 Nomenclature of Amyloidosis
ABPP, Amyloid β protein precursor; GI, gastrointestinal; SAA, serum amyloid A.
From Gertz MA, Lacy MQ, Dispenzieri A: Immunoglobulin light chain amyloidosis (primary amyloidosis, AL). In Gertz MA, Greipp PR, editors: Hematologic malignancies: Multiple myeloma and related plasma cell disorders. New York, 2004, Springer-Verlag, p 157. Used with permission of Mayo Foundation for Medical Education and Research.
Table 39-2 Syndromes in Primary Amyloidosis
| Syndrome | Patients (%) |
|---|---|
| Nephrotic or nephrotic and renal failure | 30 |
| Hepatomegaly | 24 |
| Congestive heart failure | 22 |
| Carpal tunnel | 21 |
| Neuropathy | 17 |
| Orthostatic hypotension | 12 |
From Gertz MA, Lacy MQ, Dispenzieri A: Amyloidosis. In Mehta J, Singhal S, editors: Myeloma. London, 2002, Martin Dunitz Ltd., p 445. Used with permission.
Figure 39-1 A, Bone marrow biopsy specimen showing thickened large and small vessels caused by amyloid deposition. B, Rectal biopsy specimen demonstrates amyloid deposits (left) with Brunner glands (right). (Congo red; original magnification, ×100.)
Diagnostic Pathway for Primary Amyloidosis
Consider primary amyloidosis in patients with
Confirm diagnosis histologically
Melphalan–dexamethasone–lenalidomide
NT-pro-BNP, N-terminal pro-brain natriuretic peptide.
Table 39-3 Results of High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Amyloidosis
ARF, Acute renal failure; CHF, congestive heart failure; CMV, cytomegalovirus; CR, complete response; GI, gastrointestinal; MI, myocardial infarction; NA, not available; PR, partial response.
Modified from Gertz MA, Lacy MQ, Dispenzieri A: Immunoglobulin light chain amyloidosis (primary amyloidosis, AL). In Gertz MA, Greipp PR, editors: Hematologic malignancies: Multiple myeloma and related plasma cell disorders. New York, 2004, Springer-Verlag, p 157. Used with permission of Mayo Foundation for Medical Education and Research.
From Gertz MA, Lacy MQ, Dispenzieri A: Immunoglobulin light chain amyloidosis (primary amyloidosis, AL). In Gertz MA, Greipp PR, editors: Handbook of multiple myeloma and related cell disorders. New York: Springer-Verlag, 2010. By permission of Mayo Foundation for Medical Education and Research.
Risk-Adapted Approach to Chemotherapy Dosing in Stem Cell Transplant Recipients
Melphalan dosing: as a function of risk group and age
| Good Risk | Intermediate Risk | Poor Risk |
|---|---|---|
| 200 mg/m2 if ≤60 | 140 mg/m2 if ≤50 | Standard therapy |
| 140 mg/m2 if 61-70 | 100 mg/m2 if 51-60 | Clinical trials |
| 100 mg/m2 if ≥71 |
Table 39-4 Criteria for Amyloid-Related Organ Responses to Treatment*
NT-pro-BNP, N-terminal pro–brain natriuretic peptide; NYHA, New York Heart Association.
* If organ function neither improves nor worsens, it is graded as stable.
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2 Sanchorawala V, Skinner M, Quillen K, et al. Long-term outcomeof patients with AL amyloidosis treated with high-dose melphalanand stem-cell transplantation. Blood. 2007;110:3561. Epub 2007
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6 Mhaskar R, Kumar A, Behera M, et al. Role of high-dose chemotherapy and autologous hematopoietic cell transplantation in primary systemic amyloidosis: A systematic review. Biol Blood Marrow Transplant. 2009;15:893.
7 Girnius S, Seldin DC, Skinner M, et al. Short and long-term outcomeof treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis. Ann Hematol. 2010;89:579.
8 Saba N, Sutton D, Ross H, et al. High treatment-related mortality in cardiac amyloid patients undergoing autologous stem cell transplant. Bone Marrow Transplant. 1999;24:853.
9 Sezer O, Schmid P, Shweigert M, et al. Rapid reversal of nephrotic syndrome due to primary systemic AL amyloidosis after VAD and subsequent high-dose chemotherapy with autologous stem cell support. Bone Marrow Transplant. 1999;23:967.
10 Gertz MA, Lacy MQ, Gastineau DA, et al. Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL). Bone Marrow Transplant. 2000;26:963.
11 Reich G, Held T, Siegert W, et al. Four patients with AL amyloidosis treated with high-dose chemotherapy and autologous stem cell transplantation. Bone Marrow Transplant. 2001;27:341.
12 Sanchorawala V, Wright DG, Seldin DC, et al. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001;28:637.
13 Perz J, Schoenland S, Egerer G, et al. High dose melphalan and autologous stem cell transplantation after VAD chemotherapy for treatment of systemic light chain amyloidosis [abstract]. Blood. 2001;98:397b.
14 Blum W, Brown RA, Khoury H, et al. Primary amyloidosis (AL) patients with significant organ dysfunction treated with conventional chemotherapy followed by single-dose total body irradiation (TBI) and autologous peripheral blood stem cell transplant (PBSC) then IFN-amaintenance: Tolerance and efficacy [abstract]. Blood. 2001;98:684a.
