title: Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia.
abstract: Eradication of minimal residual disease (MRD) after allotransplantation in persons with chronic lymphocytic leukemia (CLL) is associated with lower rates of relapse. Rapid engraftment of donor lymphocyte elements can contribute to MRD control, but it remains unclear whether this strategy will benefit patients. In this study, we report the incidence of MRD eradication and graft-versus-host disease (GvHD) in persons with rapid versus later donor T lymphocyte engraftment after lymphodepleting chemotherapy and reduced intensity conditioning (RIC) allotransplantation. Twenty-seven subjects received lymphodepleting chemotherapy to facilitate donor engraftment followed by fludarabine and cyclophosphamide RIC and a blood cell allograft. MRD was monitored by multicolor flow cytometry after transplantation. Complete donor T lymphoid chimerism (TLC) and myeloid chimerism (MC) were achieved in 25 subjects at a median of 28 days (range, 14-60 days) and 21 days (range, 14-180 days), respectively. Achieving complete donor TLC by day 14 versus day 28 or later correlated with occurrence of grade 2 or higher acute GvHD (90% [95% confidence interval {CI}, 78-100%] versus 35% [95% CI, 16-54%]; p = 0.014) and better control of MRD in the bone marrow at day 100, median 0% (range, 0-0.1%) versus 8.5% (range, 0-92%; p = 0.016). Among 11 persons with early donor TLC, none had progressive disease, and seven died of treatment -related mortality (TRM). In persons with later development of TLC, 8 of 16 had progressive disease and 2 died of TRM. Time to donor myeloid chimerism had no effect on outcomes. Rapid establishment of donor TLC resulted in more complete eradication of early MRD, but greater incidence of acute GvHD and TRM in persons with CLL undergoing RIC allotransplantation.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. shafferbc@mail.nih.gov
authors.forename: Brian C
authors.initials: BC
authors.lastname: Shaffer
authors.forename: Marko
authors.initials: M
authors.lastname: Modric
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Diane C
authors.initials: DC
authors.lastname: Arthur
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Robert P
authors.initials: RP
authors.lastname: Gale
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bishop
authors.forename: Steven Z
authors.initials: SZ
authors.lastname: Pavletic
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000628:therapy; D020544:Graft vs Leukemia Effect; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation; D012189:Retrospective Studies; D013601:T-Lymphocytes; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous