Favorable Chronic Graft-Versus-Host-Disease (GVHD), Event-Free (EFS), and Overall Survival (OS) Rates Following Partially CD3-Depleted Alternative Donor Peripheral Stem Cell Transplantation (PSCT) for Pediatric Hematologic Malignancies

Most children who may benefit from stem cell transplantation lack matched family donors. We present follow-up data from a multi-institutional study of a partial CD3-depletion strategy for unrelated or partially matched related donor PSCT in children with hematologic malignancies. We enrolled eligible patients ages 0-21 years on a single-arm multi-institutional trial of alternative donor PSCT with CD3/CD19-depletion using the Miltenyi CliniMACS device, adding back up to 5x105 CD3+cells/kg. All patients received myeloablative thiotepa, cyclophosphamide, and TBI or busulfan. Events were defined as donor lymphocyte infusion, second transplant, non-relapse mortality (NRM), relapse or death. Single-agent calcineurin-inhibitor GVHD prophylaxis (cyclosporine IV then tacrolimus PO) was discontinued by d+150 in the absence of GVHD. CMV, EBV and adenovirus PCR were surveyed weekly until d+100. We enrolled 84 patients at two centers between April 2005 – February 2015 (Table 1). Mean follow-up was 1040 ± 911 days (Table 2). Two patients (2.4%) experienced primary graft failure. Relapse occurred in 23 patients (27.4%), 18 of whom died, and 17 patients (20.4%) experienced TRM. Three-year OS was 61.8% (95% CI 50.2 –71.4%) and EFS 52.0% (95% CI 40.3 – 62.4%). Age ≥15 years was associated with decreased OS (p=0.037) and EFS (p=0.046). Chronic GVHD (cGVHD) was associated with increased OS (p=0.003) and EFS (p=0.099). Second remission was associated with decreased EFS (p=0.028). Partially CD3-depleted alternative donor PSCT NRM, OS, and EFS compare favorably with previously published studies of T-replete PSCT, and cGVHD had a protective effect on both OS and EFS. Historically, T-replete PSCTs have an inverse ratio of extensive:limited grade cGVHD, which may explain the relatively low relapse and TRM rates in our study despite similar overall rates of cGVHD. Partial T cell-depletion may expand donor options for these children, and more precise T cell-depletion strategies, such as alpha/beta TCR- or CD45RA-depletion, merit further investigation.Table 1Baseline characteristicsN=84Age in years, mean ± SD (range)12.7 ± 4.9 (1.6-21.2)Female, n (%)39 (52)Diagnosis, n (%) ALL/T-LL46 (54.8) AML26 (31) MDS12 (14.3)Remission status, n (%) CR1/MDS41 (48.8) CR227 (32.1) other16 (19.1)HLA mismatch, n (%) None25 (30.5) 1 allele4 (4.9) 1 antigen16 (19.5) >1 antigen or allele37 (45.1) CD34+ dose x106/kg, mean ± SD (range)6.36 ± 3.24 (1-19.6) CD3+ dose x105/kg, mean ± SD (range)2.44 ± 2.09 (0.49-9.83) Open table in a new tab Table 2OutcomesDays to engraftmentmean ± SDNeutrophils15 ± 3.2Platelets19.3 ± 8.2Acute GVHDn, (%)None24 (28.9)Grade I27 (32.5)Grade II14 (16.9)Grade III8 (9.6)Grade IV10 (12.1)Chronic GVHD None48 (57.1) Limited26 (31) Extensive10 (11.9)Viral reactivation CMV22 (26.5) EBV17 (20.2) Adeno24 (28.6) HHV625 (29.8)Mortality NRM17 (20.2) Early NRM (