Publication Date:
2015-12-03
Description:
Background. T-cell depletion is often used to reduce graft-vs-host disease in haploidentical donor hematopoietic cell transplantation (HCT). However, the absence of adoptively transferred T-cells may increase graft failure, relapse, and infection. Novel methods have been developed to more selectively deplete naïve T cells and preserve memory T cells. Depletion of CD45RA+ cells can provide robust early recovery of diverse memory T-cell populations in haploidentical donor transplantation, and may provide increased immunity against viral infections. Likewise, the provision of additional donor NK cells may reduce viral complications. Patients and Methods. Sixty-seven patients received initial allogeneic HCT on 3 consecutive IRB approved haploidentical donor HCT trials at St. Jude Children's Research Hospital from 2005 to 2015. CD3-depletion was used in 41 recipients, and CD45RA-depletion was used in 26. All patients received similar preparative doses of fludarabine, thiotepa, and melphalan. Patients with CD3-depleted grafts received OKT3 (n=20) or Campath (n=21), and all 41 received rituximab on Day 0 as EBV prophylaxis. Patients with CD45RA-depleted grafts (n=26) did not receive antibody therapy, but instead received total lymphoid irradiation and a dose of cyclophosphamide added to the preparative backbone. Donor NK cells were given Day +6. Peripheral blood was tested for CMV, EBV, and adenovirus using quantitative PCR at least weekly until day +100, and then as indicated. The first 180 days post-HCT were evaluated. Fisher's exact test was used to compare two proportions. Results. Patients with CD3-depletion received a median 0.04 (range: 0.01 - 0.15) x 106 CD3+ cells/kg, and patients with CD45RA-depletion received a median 80.07 (range: 16.08 - 528.52) x 106 CD3+ cells/kg. CMV reactivation occurred in 23 of 41 patients (56.1%) with CD3-depletion and 5 of 26 patients (19.2%) with CD45RA-depletion (p=0.005). Differences occurred predominantly in those CMV seropositive recipients who received grafts from CMV seropositive donors, as CMV was detected in 22 of 24 (91.7%) +/+ patients with CD3-depletion and 4 of 11 (36.4%) +/+ patients with CD45RA-depletion (p=0.001). Of the 23 patients with CMV after CD3-depletion, the peak viral load was a median 4.49 log10 copies/mL blood (range:
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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