acute graft vs. host disease (GVHD), and chronic GVHD. The primary analysis tested the impact of mismatch at HLA-A, B, C and DRB1. Secondary analyses examined HLA locus-specific effects, allele vs. antigen mismatch, and the impact of DPB1 and DQB1 mismatch. Additional patient, disease, and HCT variables were considered in multivariate analyses. A p value < 0.01 was considered significant. Results: Of the study population (n¼8,003), cases were 8/8 (n¼5,449), 7/8 (n¼2,071), or 6/8 (n¼483) matched. Median follow up for surviving patients was 49 (3-151) months. The study population was 88% Caucasian, 67% KPS 90-100, 77% acute leukemia and only 14% CML, 56% peripheral blood, and 43% non-TBI myeloablative conditioning. Of the total, 20% were from 1999-2002, 32% 2003-2006, and 49% from 2007- 2011. In the primary analysis, HLA mismatch (6-7/8) conferred significantly increased risk for grade II-IV and III-IV acute GVHD, chronic GVHD, and TRM, and worsened DFS and OS compared to HLA matched cases (8/8). Malignancy relapse was not affected by HLA mismatch at A, B, C, or DRB1. The 6/8 cases had significantly worse TRM than 7/8 cases. The adverse impact of HLA mismatch on OS was greatest among those with early or intermediate stage disease. Single mismatch at HLA-A, B, and C increased the risk for acute GVHD, TRM, and worsened OS. While single antigen mismatch at HLA-B increased risk for grade II-IV acute GVHD over single allele mismatch at eB, no other differences were detected between allele or antigen mismatch. Among 8/8 matched cases, DPB1 mismatch was associated with increased grade II-IV and III-IV acute GVHD and decreased relapse, and DQB1 mismatch was associated with increased grade II-IV acute GVHD; these effects were not observed among 7/8 cases. DPB1 and DQB1 mismatch among 7/8 or 8/ 8 cases had no effect on OS or DFS. Conclusions: Despite improvements in survival after unre- lated donor HCT over time, donor-recipient HLA disparity remains a major source of GVHD and mortality. 6 Clinical Responses in Patients Infused with T Lymphocytes Redirected to Target Kappa-Light Immunoglobulin Chain Carlos A. Ramos 1, 2 , Barbara Savoldo 3, 4 , Enli Liu 3 , Adrian P. Gee 4, 5 , Zhuyong Mei 3 , Bambi Grilley 3, 4 , Cliona M. Rooney 3, 4 , Helen E. Heslop 2, 3, 4 , Malcolm K. Brenner 2, 3, 4 , Gianpietro Dotti 3 . 1 Center for Cell and Gene Therapy, Dept. of Medicine, Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital, Houston, TX; 2 Houston Methodist Hospital, Houston, TX; 3 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; 4 Texas Children’s Hospital, Houston, TX; 5 Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital, Houston, TX Adoptive transfer of T cells with a CD19-specific chimeric an- tigen receptor (CAR) to treat B-cell malignancies shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan-B cell marker, causes depletion of normal B cells and consequent severe hypogammaglobu- linemia. In order to target B-cell malignancies more selectively, we have taken advantage of the clonal restriction of mature B-cell malignancies, which express either a k or a l-light immunoglobulin chain. We generated a CAR specific for k-light chain (CAR.k) to selectively target k + lymphoma/leukemia cells, while sparing the normal B cells expressing the non-targeted l-light chain, thus minimizing the impairment of humoral immunity. After validation in preclinical experiments, we designed a phase I clinical trial in which patients with re- fractory/relapsed k + NHL/CLL are infused with autologous T cells expressing a CAR.k that includes a CD28 costimulatory domain. The protocol also allows for the inclusion of patients with multiple myeloma (MM) with the aim of targeting pu- tative myeloma initiating cells. Three dose levels (DL) are being assessed: 0.2 (DL1), 1 (DL2) and 2 (DL3) Â10 8 T cells/m 2 . Tcells were generated for 13 patients by activating autologous PBMC with OKT3 (n¼5) or CD3/CD28 monoclonal antibodies (n¼8). In 2 patients with >95% circulating CLL cells, CD3 positive selection was performed using CliniMACS. After transduction, T cells (1.2Â10 7 Æ0.5Â10 7 ) were expanded ex vivo for 18Æ4 days in the presence of IL-2 to reach sufficient numbers for dose escalation. CAR expression was 81%Æ13% by flow cytometry. Products were composed predominantly of CD8 + cells (78%Æ10%). CAR + T cells specifically targeted k + tumors (specific lysis by 51 Cr release 79%Æ10%, 20:1 E:T ratio) but not k e tumors (11%Æ7%) or the NK-sensitive cell line K562 (26%Æ13%). Tenpatients were treated so far: 2 on DL1, 3 on DL2 and 5 on DL3. Any other treatments were discontinued at least 4 weeks prior to T-cell infusion and patients with ALC >500 received 12.5 mg/kg cyclophosphamide 4 days before infusion. Infusions were well tolerated without side effects. A CAR.k-specific Q-PCR assay showed that molecular signals peaked 1-2 weeks post infusion and remained detectable for at least 6 weeks and up to 9 months in 1 patient. Of the 5 patients with relapsed NHL, 2 entered complete remission (after 2 and 3 infusions at DL1 and DL3, respectively), 1 had a partial response and 2 progressed; 3/3 patients with MM have had stable disease for 2,11 and 17 months, associated with up to 38% reduction in their paraprotein; and 2/2 patients with CLL progressed before or shortly after the 6 week evaluation. In conclusion, our data indicate that infusion of CAR.k + T cells is safe at every DL and can be effective in patients with k + lymphoma. Abstracts / Biol Blood Marrow Transplant 20 (2014) S22eS26 S26