title: Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.
abstract: Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.
authors: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors: Nobuhiko
authors: N
authors: Imahashi
authors: Haruhiko
authors: H
authors: Ohashi
authors: Seitaro
authors: S
authors: Terakura
authors: Kotaro
authors: K
authors: Miyao
authors: Reona
authors: R
authors: Sakemura
authors: Tomonori
authors: T
authors: Kato
authors: Masashi
authors: M
authors: Sawa
authors: Emi
authors: E
authors: Yokohata
authors: Shingo
authors: S
authors: Kurahashi
authors: Yukiyasu
authors: Y
authors: Ozawa
authors: Tetsuya
authors: T
authors: Nishida
authors: Hitoshi
authors: H
authors: Kiyoi
authors: Koichi
authors: K
authors: Watamoto
authors: Akio
authors: A
authors: Kohno
authors: Masanobu
authors: M
authors: Kasai
authors: Chiaki
authors: C
authors: Kato
authors: Hiroatsu
authors: H
authors: Iida
authors: Tomoki
authors: T
authors: Naoe
authors: Koichi
authors: K
authors: Miyamura
authors: Makoto
authors: M
authors: Murata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D046528:Chimerism / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D019172:Transplantation Conditioning / Q000009:adverse effects*; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan