Open AccessTacrolimus initial steady state level in post-transplant cyclophosphamide-based GvHD prophylaxis regimens
Author(s) -
Janny M. Yao,
Dongyun Yang,
Mary C. Clark,
Salman Otoukesh,
Thai M. Cao,
Haris Ali,
Shukaib Arslan,
Ibrahim Aldoss,
Andrew Artz,
Idoroenyi Amanam,
Amandeep Salhotra,
Vinod Pullarkat,
Karamjeet S. Sandhu,
Anthony S. Stein,
Guido Marcucci,
Stephen J. Forman,
Ryotaro Nakamura,
Monzr M. Al Malki
Publication year - 2021
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/s41409-021-01528-y
Subject(s) - medicine , tacrolimus , cyclophosphamide , calcineurin , chemotherapy , intensive care medicine , transplantation
Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) as graft-versus-host disease (GvHD) prophylaxis post-hematopoietic cell transplantation (HCT) is safe and effective. Optimal serum levels of TAC in this combination remain undetermined. We hypothesized that TAC at initial steady state (TISS) of <10 ng/mL could promote optimal transplant outcomes and prevent TAC-associated toxicities. We retrospectively analyzed a consecutive case series of 210 patients who received PTCy/TAC-based prophylaxis post-HCT from 1/2013-6/2018. Patients received HCT from haploidentical (n = 172) or mismatched donors (n = 38), and flat dose (FD) or weight-based dose (WBD) TAC. Twenty-four-month overall survival (OS), disease free survival (DFS), and relapse rate (RR) were 61%, 56%, and 22%, respectively, in TISS < 10 ng/mL cohort (n = 176), and 50%, 43%, and 35%, respectively, in TISS ≥ 10 ng/mL cohort (n = 34) (OS, P = 0.71; DFS, P = 0.097; RR, P = 0.031). OS, DFS, RR, non-relapse mortality, acute GvHD grade II-IV, grade III-IV or chronic GvHD by TISS were similar in multivariable analysis. TISS ≥ 10 ng/mL conferred increased risk of viral infection (P = 0.003). More patients receiving FD vs. WBD had TISS < 10 ng/mL (P = 0.001). Overall, TISS < 10 ng/mL early post HCT conferred similar survival outcomes and lowered risk of viral infection and toxicities compared to TISS ≥ 10 ng/mL.