Evaluating the use of Multiparametric Flow Cytometry in establishing the presence of Minimal Residual Disease in systemic AL amyloidosis: a report of eight patients

Autor: Anna Baginska, Dorota Rowczenio, Mark R.E. Coyne, Ashutosh D. Wechalekar
Rok vydání: 2015
Předmět:
Zdroj: Clinical Lymphoma Myeloma and Leukemia. 15:e185
ISSN: 2152-2650
Popis: The identification of Minimal Residual Disease (MRD) is becoming increasingly important for defining outcomes in haematological malignancies; particularly in independently predicting prognosis in myeloma. The role of MRD analysis in systemic AL amyloidosis is less well established. Patients with systemic AL amyloidosis at diagnosis have a lower clonal burden than that seen in myeloma. Moreover, upfront autologous transplantation even in the era of novel therapies continues to provide a more durable remission than that seen in myeloma. Here, as a proof of principle, eight patients with systemic AL amyloidosis in complete response (CR) underwent MRD analysis. MRD analysis was completed if CR was achieved, usually six months from induction treatment. Induction treatments included two patients treated with cyclophosphamide, thalidomide, dexamethasone and six patients with cyclophosphamide, bortezomib and dexamethasone. Two of the six patients that had received CVD based treatment underwent consolidation autologous transplantation. Bone marrow samples were immunophenotyped with eightcolour multiparametric flow cytometry (MFC). The expression of CD138 and CD38 was used to gate the plasma cell population. Patients were identified as having residual disease if a discreet population of phenotypically aberrant plasma cells comprising 50 events were identified in the 500, 000 event file (0.01% limit of detection). An aberrant phenotype was defined as a lack of CD19 expression, strong CD138 expression, weak CD27 expression, and or weak CD45 expression. Interestingly, none of the eight patients demonstrated MRD negativity. All patients demonstrated a measurable clone despite evidence of CR, including two patients who had an autologous bone marrow transplantation. CD117 and CD81 expression failed to provide any additional discrimination between polyclonal and clonal plasma cells. Moreover, the spread between CD81 positive and negative populations was difficult to distinguish in certain patients. In conclusion, this proof of principle study supports MFC as an effective measurement of MRD in patients with systemic AL amyloidosis. The finding that all patients demonstrate MRD positivity raises difficulties in rationalizing if MRD negativity is necessary for a durable remission in systemic AL amyloidosis. To address this further, an adequately powered study randomizing MRD positive patients to further treatment or no treatment may be necessary. PO-179 Hospitalization Rates for Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database A.A. Yusuf, T. Bovitz, W. Werther, D. Felici, M. Mahue, K. Bridges, Y. Peng Chronic Disease Research Group, Minneapolis, MN, USA; University of Minnesota, Minneapolis, MN, USA; Onyx Pharmaceuticals Inc., an Amgen Subsidiary, South San Francisco, CA, USA
Databáze: OpenAIRE