Reversal of Low Donor Chimerism after Hematopoietic Cell Transplantation Using Pentostatin and Donor Lymphocyte Infusion: A Prospective Phase II Multicenter Trial

Biol Blood Marrow Transplant. 2018 Feb;24(2):308-313. doi: 10.1016/j.bbmt.2017.10.016. Epub 2017 Oct 12.

Abstract

In a multicenter, prospective, phase II study we evaluated the safety and efficacy of pentostatin followed by donor lymphocyte infusion (DLI) in patients with low donor Tcell chimerism after allogeneic hematopoietic cell transplantation (HCT). Thirty-six patients with low donor blood CD3 chimerism were enrolled in this study. Thirty-five patients received a total of 41 DLIs after a dose of pentostatin, and 1 patient received pentostatin only. Median donor CD3 chimerism prompting the initiation of pentostatin and DLI was 28% (range, 5% to 47%). Responses (defined by increases in donor CD3 chimerism ≥10% maintained to day 56 post-DLI) were seen in 16 patients (44.4%) with a median rise in CD3 donor chimerism to 64% (range, 48% to 100%). There was a trend for better responses among 21 patients who received first treatment within 100 days after transplant (57% response rate) compared with15 patients who received first treatment more than 100 days after HCT (27% response rate, P = .07). Fourteen patients (39%) developed grades II to IV acute graft-versus-host disease (GVHD) at a median of 10 days (range, 0 to 83) after DLI. Ten patients (28%) developed extensive chronic GVHD. Seventeen patients (47%) developed new grade 4 cytopenias after DLI. There was no difference in relapse between nonresponders and responders. Twenty-eight patients (78%) died, most (n = 21) because of relapse. Five of 16 responders (31%) are alive, all disease-free, at a median of 60 months (range, 21 to 132) after DLI. Six of 20 nonresponders (30%) are alive at a median of 47 months (range, 16 to 100) after DLI, 3 in complete remission. Pentostatin and DLI had acceptable toxicity and appeared to increase low donor CD3 chimerism after HCT but had no impact on mortality.

Keywords: Donor lymphocyte infusion (DLI); Hematopoietic cell transplantation (HCT); Low donor Tcell chimerism; Pentostatin.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / analysis
  • Chimerism*
  • Female
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Transfusion / adverse effects
  • Lymphocyte Transfusion / methods*
  • Male
  • Middle Aged
  • Pentostatin / administration & dosage*
  • Pentostatin / pharmacology
  • Survival Analysis
  • Treatment Outcome

Substances

  • CD3 Complex
  • Pentostatin