Early Lymphocyte Recovery Predicts Superior Survival after Autologous Hematopoietic Stem Cell Transplantation for Patients with Primary Systemic Amyloidosis Luis F. Porrata, Morie A. Gertz, Mark R. Litzow, Martha Q. Lacy, Angela Dispenzieri, David J. Inwards, Stephen M. Ansell, Ivanna N.M. Micallef, Dennis A. Gastineau, Michele Elliott, William J. Hogan, Suzanne R. Hayman, Ayalew Tefferi, and Svetomir N. Markovic Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota ABSTRACT Purpose: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown. Experimental Design: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/ML based on our previous observations. Results: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 z 500 cells/ML compared with patients with an ALC-15 < 500 cells/ML (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were signifi- cantly better for the 59 patients that achieved an ALC-15 z 500 cells/ML compared with 86 patients with ALC-15 < 500 cells/ML (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival. Conclusions: ALC-15 z 500 cells/ML is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis. INTRODUCTION Day 15 absolute lymphocyte count (ALC-15) after autologous stem cell transplantation (ASCT) has been reported as a powerful independent prognostic indicator of clinical outcomes for metastatic breast cancer (1, 2) and multiple malignant hematologic (3–8) conditions including multiple myeloma (6). Because of the superior survival observed in multiple myeloma (MM) patients achieving higher ALC-15 (z500 cells/AL) post-ASCT, we hypothesized that ALC-15 may also affect survival in another plasma cell dyscrasia treated with ASCT, primary systemic amyloidosis. Herein we present the results of our study evaluating the role of ALC-15 following ASCT in patients with amyloidosis. MATERIALS AND METHODS Patient Population. Between 1996 and 2003, a total of 173 ASCT have been done at the Mayo Clinic for patients with amyloidosis. The diagnosis of amyloidosis was made as previously described (9). Clinical MM was defined as the presence of an M protein in serum or urine associated with lytic bone disease or z30% monoclonal plasma cells in the bone marrow (10). A total of 145 of 173 (84%) consecutive patients were eligible for the study. Twelve patients were excluded because they had not achieved their >100 days follow-up visit due to recent transplant; six patients died before day 15 post-ASCT and 10 patients had a concurrent diagnosis of another malignancy (8 patients with multiple myeloma, 1 patient with Waldrestrom macroglobulinemia, and 1 patient with lymphoplasmacytic lymphoma). Data for this retrospective study were prospectively collected over time and entered into a computerized database. Response to therapy, relapse, and survival data are updated continuously. No patients were lost to follow-up. All patients gave written, informed consent allowing the use of their medical records for medical research. Approval of the study was obtained from the Mayo Clinic Institutional Review Board and was in accordance with U.S. federal regulations and the Declaration of Helsinki. End Points. The primary end point of the study was to assess the impact of ALC-15 on overall survival (OS) and progression-free survival (PFS) from the time of transplant. Secondary end point was to determine the agreement, as well as the correlation between the autograft absolute lymphocyte count (A-ALC) and ALC-15 in amyloidosis. The ALC-15 was obtained from the standard complete blood cell count, and the infused A-ALC for each apheresed unit collection was calculated as follows: A-ALC = [(% collection lymphocytes)  (absolute WBC)]/kg. Prognostic Factors. Prognostic factors for post-trans- plant OS and PFS evaluated in this study included age, albumin, alkaline phosphatase, h-2 microglobulin, bone marrow plasma Received 8/13/04; revised 10/7/04; accepted 10/8/04. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Luis F. Porrata, Department of Hematology and Internal Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-284-3158; Fax: 507-266-4972; E-mail: porrata.luis@mayo.edu. D2005 American Association for Cancer Research. Vol. 11, 1210–1218, February 1, 2005 Clinical Cancer Research 1210