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329 ALEMTUZUMAB DOSING BY RECIPIENT WEIGHT IS IMPORTANT FOR REDUCED-INTENSITY CONDITIONING FOR ALLOGENEIC TRANSPLANTATION.
  1. C. L. Hardy1,
  2. J. C. Files1,
  3. C. L. Bigelow1,
  4. S. L. Elkins1,
  5. V. E. Herrin1
  1. 1Department of Medicine, University of Mississippi Medical Center, Jackson, MS

Abstract

From June 2002, to August 2006, our institution used reduced-intensity conditioning (RIC) regimens for allogeneic transplantation of 40 adult at-risk older patients or patients with comorbid conditions. Malignancies included multiple myeloma, AML, CML, NHL, MDS, CLL, and one renal cell carcinoma. Thirteen (32%) were in CR at time of transplant, whereas 27 (68%) had relapsed or refractory disease. Median age was 50 years (range 24-66) and median follow-up was 8 months (1-36 months). Degree of HLA match at A, B, and DR was 6/6 or better for 31 patients and either single antigen or allele mismatches for the others. Three RIC regimens consisted of intravenous infusions of: fludarabine 30 mg/m2 × 5 days and melphalan 140 mg/m2 × 1 day in all groups, and of Alemtuzumab 20 mg/d × 5 days (protocol 1), × 3 days (protocol 2), and × 2 days (protocol 3). Twenty-three patients received MUD products and 17 received MRD products; cell source was bone marrow (17), PBSC (19), cord blood (1), and combination products (3). All patients received an adequate CD34+ cell dose or TNC dose (cord blood transplant). GVHD prophylaxis was tacrolimus tapering after day +100 and mycophenolate mofetil tapering after day +30. Determination of the optimal dose of alemtuzumab was a goal of this study. All patients except one achieved a WBC graft. Relapse or disease progression occurred in only 37% of protocol 3, 40% of protocol 2, and 67% of protocol 1. Although alemtuzumab doses were given in a standard fashion not adjusted for body weight or surface area, it was found that a lack of consideration of patient size did not represent the intent of the given protocols. Weight-based alemtuzumab dose adjustment showed that a much broader dose range than expected had occurred. Those receiving protocol 1 were in a dose range of 1.01 to 1.90 mg/kg; for protocol 2, the range was 0.36 to 1.08 mg/kg; for protocol 3, the range was 0.36 to 0.70. The median dose of alemtuzumab for the cohort was 0.68 mg/kg. A clustering of acute GVHD grades I to II appeared below the median dose at approximately 0.55 mg/kg; only one patient had grade IV GVHD. In summary, these data indicate that using the patient's body weight in the determination of an optimal alemtuzumab dose is a more reasonable approach to developing and standardizing RIC protocols with this drug.

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