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
Biology of Blood and Marrow Transplantation(2016)
Abstract
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 (
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Key words
Hematopoietic Cell Transplantation,Hematologic Malignancies
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