Work

CD34+ Stem Cell Selection And CD3+ Addback For Pediatric Patients Receiving Matched Unrelated Adult Donor (MUD) Peripheral Blood Stem Cell Transplantation (PBSCT) Is Associated With Rapid Myeloid Engraftment And Low Risk Of Both Post-Transplant Lymphoproliferative Disorder (PTLD) And Grade 2-4 Acute Graft Versus Host Disease (aGVHD)

Year: 2010

Type: article

Abstract: Positive selection of CD34 stem cells is a method of depletion of T cells responsible for severe aGVHD (Lang et al., Blood, 2003). CD34-selected haploidentical SCT in children with leukemia and nonmalignant diseases is associated with sustained engraftment and low risk of aGVHD (Lang/Handgretinger, BMT, 2008). Myeloablative conditioning (MAC) followed by CD34-selected MUD PBSCT with a CD3 dose of 5×105/kg carries high risk of chronic GVHD (Bunin et al., BMT, 2006). We sought to determine engraftment, survival, immune reconstitution (IR) and frequency of PTLD and GVHD in pediatric patients at risk of severe aGVHD following CD34-selected MUD PBSCT. The Isolex 300i (Nexell, Irvine, CA) immunomagnetic cell selection system was used for CD34 selection with a goal of achieving ≥5 x106 CD34/kg PBSC. T cells were added back to reach a total CD3 dose of 1.0-2.6×105/kg. Conditioning was MAC in 57% vs. reduced intensity (RIC) in 43%. GVHD prophylaxis consisted only of tacrolimus. Supportive care was as we have previously described (Bradley/Cairo, BMT, 2007). Fourteen pts, median f/u of 451 d, median age of 15.0 yrs (10-23); 1:1 M:F, HLA match 29% 10/10, 36% 9/10, 26% 8/10, 64% malignant (56/44% poor/average risk). Cell selection resulted in median CD34 recovery of 59% and 4.33 CD3 log depletion (Table 1). All 14 pts engrafted neutrophils (median day 14, range 9-27). Of 12 evaluable pts, 10 (83%) engrafted platelets (median day 32, range 21-44). No pts developed PTLD. One pt (7%) developed CMV infection. Probabilities of grade II-IV aGVHD and chronic GVHD were 14.3% (95% CI 0-31%) and 36.4% (1-59%) respectively. Day 100 mortality was 7%. The probability of 1-year OS was 84% (67-100%). Of 9 pts with acute leukemia, 3 (33%) died from progressive disease. CD3, CD4, CD8, CD19 and CD56 counts at day +180/365 were normal in 20/38%, 0/13%, 40/63%, 70/100% and 100/100% of pts, respectively. Engraftment, GVHD, fungal infection and IR did not differ with respect to conditioning; MAC recipients had higher risk of viral infection (p=.02) and mortality (5/8 in MAC vs. 0/6 in RTC, but p=.09) Rapid neutrophil engraftment, no PTLD, minimal grade II-IV aGVHD and high day 100 and overall survival were observed. Depletion of B and T cells during CD34 selection may be responsible for the relatively slow recovery of T cells post-transplant. These results support the continued investigation of CD34-selected MUD PBSCT in pediatric recipients.Table 1Stem cell selection data for patients undergoing CD34+-selected MUD PBSCTMedianRangePre-Selection CD34+ x 106 total cells438.79239.75 - 886.41Post-Selection CD34+ x 106 total cells299.57131.81 - 521.94CD34+ Percent Recovery58.8842.93 - 85.58Final Infused CD34+ x 106/kg5.062.02 - 13.30Pre-Selection CD3+ x 108/kg4.742.30 - 20.69Post-Selection CD3+ x 105/kg0.220<0.001 - 2.450CD3+ Log Depletion4.332.45 - ∗CD3+ Addback x 105/kg1.0030 - 2.170Final Infused CD3+ x 105/kg1.5000.093 - 2.600∗Post-selection CD3+ was below the threshold of detection for two grafts. Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2009.12.280