Characteristics of CD34-Enriched Products Processed at Multiple Centers Using the CliniMACS System - BMT CTN 0303 Carolyn Keever-Taylor, Steven M Devine, Robert J Soiffer, Shelly L Carter, Marcelo Pasquini, Parmeswaran Hari, Anthony Stein, Hillard M. Lazarus, Charles Linker, Ed Stadtmauer, and Richard J O Reilly on behalf of the Blood and Marrow Transplant Clinical Trials Network The BMT CTN is co-sponsored by the NHLBI and NCI.
Introduction Graft T cell depletion (TCD) has shown efficacy in the treatment of Acute Myelogenous Leukemia (AML) in complete remission in single-center trials Although a high rate of engraftment, low rate of relapse and minimal transplant related complications, were reported, the studies differed in patient selection criteria and used methods achieving varying degrees of TCD BMT CTN 0303 was designed to use standard patient selection criteria, a uniform method for TCD, and no post transplant pharmacological GVHD prophylaxis.
Designed to use: BMT CTN 0303 Standard patient selection criteria Adults 18-65 in 1 st or 2 nd CR with 2 cycles HLA identical apheresis product donor Highly immunosuppressive conditioning regimen Hyperfractionated TBI to 1.375 Gy Thiotepa followed by cyclosphosphamide ATG day -4 Uniform method for extensive TCD requiring no post transplant pharmacological GVHD prophylaxis CD34-enrichment using the CliniMACS device
Objectives Primary Objective Disease Free Survival @ 6 months >75% Secondary Objectives Infusional toxicity Graft failure 1% Acute GVHD grades 3-4 5% Transplant-related mortality 10%@ day 100 PTLD Time to relapse Consistency of graft processing outcome Topic of this presentation
Product Goals CD34 Target 5.0 x 10 6 /kg Minimum 2.0 x 10 6 /kg CD3 Target <1.0 x 10 5 /kg Planned 2 apheresis collections Not more than 3 apheresis collections If <1.0 x 10 6 CD34/kg after second apheresis then 3 rd collection given without selection
Product Collection & Processing 86 apheresis collections from 44 donors underwent processing 4 product collections split for processing on two columns Split products were pooled for analysis Product collections for 2 patients pooled for processing on 1 column and analyzed as one procedure Product analysis does not include: 2 nd collections frozen for 5 patients 3 rd collections frozen for 1 patient
Overall Graft Characteristics N=44 CD34 Dose Infused/kg ( x 10 6 ) 9.4 ± 5.4 (2.4 to 31.3) CD3 Dose Infused/kg ( x 10 4 ) 1.6 ± 2.2 (0.1 to 8.8) 100% of patients achieved minimum CD34 dose 86% of patients achieved target CD34 dose 0% of patients exceeded maximum CD3 dose
Statistical Analysis Four centers performing 9-34 procedures compared individually with 4 centers performing 4 procedures Linear mixed effect model used to account for repeated measures ( 2 procedures for most patients) Pairwise comparison used Tukey-Kramer adjustment for multiple comparisons Overall P-values <0.05 indicate minimally 2 centers differ for characteristic compared
Starting TNC
Starting CD34 P=0.003 5.9 ± 4.1 x 10 8 (0.7 to 21 x 10 8 )
Starting CD3 P=NS 17.8 ± 7.3 x 10 9 (5.5 to 36.2 x 10 9 )
CD3 Log Depletion P=0.01 4.8±0.6 (3.2 to 5.9)
CD34 Purity
CD34 Recovery P=0.0005 67.9% ± 20.1% (30.3% to 125.0%)
CD34-enriched product viability P=0.0023 96.6% ± 3.8% (74.0% to 100%)
Factors Affecting Log TCD and CD34 Recovery P=0.036 P=0.015
Impurities
CD34/kg Infused by Center
CD3 Infused by Center
Summary Grafts with a consistent high degree of TCD and CD34 purity can be achieved in a multi-center setting using the CliniMACS Device for CD34- enrichment Differences in final products were not directly associated with the experience of the laboratory Approximately 70% of starting CD34+ cells are recovered CD34 recovery is improved in products with lower starting CD34+ cells Even though differences were seen between centers, all centers were able to produce products meeting the goals of the study
Contributing Centers City of Hope National Medical Center Dana Farber/Partners Cancer Center Medical College of Wisconsin Memorial Sloan-Kettering Cancer Center Ohio State University Medical Center University Hospitals of Cleveland/Case Western University of California, San Francisco University of Pennsylvania
Disclosures This trial was sponsored by NHLBI and NCI This trial also was supported in part by Miltenyi Biotec, Inc
Effect of Washes on TNC P=0.007 89.0% ± 9.2% (52.3% to 116.5%)
Effect of Washes on CD34 P=0.02 95.1% ± 18.4% (49.5% to 166.4%)