April 2011, New Publications
Four important new publications from our Program investigators:
A strong collaboration has been developed between our Program and the Heart Transplant Program at the Massachusetts General Hospital directed by Dr. Marc Semigran. Since patients with AL amyloidosis and severe heart failure often have a very short survival and poor tolerance to medications, we have worked with the MGH program to evaluate patients for combined therapy with heart transplantation followed by chemotherapy and stem cell transplantation. This is a challenging treatment protocol, but can be lifesaving for selected patients who are young enough and have enough other normal organ function to go through the combined treatment over a period of 6 to 12 months. Patients begin this process with an evaluation at BU and if appropriate are referred to the Heart Transplant team at MGH.
Dey BR, Chung S, Spitzer TR, Zheng H, MacGillivray TE, Seldin DC, MsAfee S, Ballen K, Attar E, Wang T, Shin J, Newton-Cheh C, Moore S, Sanchorawala V, Skinner M, Madsen JC, Semigran MJ: Cardiac transplantation followed by dose-intensive melphalan and autologous stem-cell transplantation for AL amyloidosis and heart failure. Transplantation, 90:905-911, 2010.
BRDey Amyloidosis Transplantation Nov2010
Dr. Vaishali Sanchorawala, Amyloid Program hematologist and director of the Stem Cell Transplant Program, has studied the effect of oral cyclic melphalan and dexamethasone treatment for AL amyloidosis in a group of 70 patients who were not eligible for treatment with high-dose intravenous melphalan and stem cell transplantation. In their study 13% of patients achieved a complete hematologic response and 25% of patients achieved a partial hematologic response. They concluded that oral mel/dex can lead to hematologic responses and clinical benefits for patients not eligible for stem cell transplant.
Sanchorawala V, Seldin DC, Berk JL, Sloan M, Doros G, Skinner M: Oral cyclic melphalan and dexamethasone for patients with AL amyloidosis. Clin. Lymphoma, Myeloma, Leukemia 10: 469-472, 2010
Dr. Elena Klimtchuk, a biophysics researcher in the Gerry Amyloid Research Laboratory, investigated the amyloid fibril-forming properties of an amyloidogenic lambda light chain using sophisticated biophysics techniques. Their novel discovery was that the constant region as well as the variable region of the light chain plays a role in the irreversible aggregation that leads to fibril formation. This finding provides an important new target for molecular therapies that will need to be less individualized than treatments focused on the variable part of the molecule.
Klimtchuk ES, Gursky O, Patel R, Laporte KL, Connors LH, Skinner M, Seldin DC: The critical role of the constant region in thermal stability and aggregation of amyloidogenic immunoglobulin light chain. Biochemistry, 49: 9848-9857, 2010.
Eprint – E Klimtchuck Critical Role of CL Region
Michael Greene, a Pathology and Lab Medicine Department graduate student working with Dr. Connors, studied a molecular chaperone called clusterin and found that it is co-deposited with light chain and transthyretin amyloid in patients’ hearts, and its levels in the blood go down in patients with amyloid cardiomyopathy. This suggests that low levels of clusterin may be a biomarker for amyloid cardiomyopathy, and could play a role in the development of disease.
Greene MJ, Sam F, Soohoo P, Patel R, Seldin DC, and Connors LH: Evidence for a functional role of the molecular chaperone clusterin in amyloidotic cardiomyopathy. J Am Path, 178(1):61-8, 2011.
eprint – Greene et al AJP 2011