422 The Blood Concentration of Tacrolimus Is Affected By Pir Following Cord Blood Transplantation

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Taro Kurihara Jr., M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Toshimitsu Ueki, M.D, PhD , Hematology, Nagano Red Cross Hospital, Nagano, Japan
HIroko Kaiume, M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Wataru Takeda, M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Takehiko Kirihara, M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Keijiro Sato, M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Yuki Hiroshima, M.D, PhD , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Masahiko Sumi, M.D, PhD , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Mayumi Ueno, M.D , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Naoaki Ichikawa, M.D, PhD , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Hikaru Kobayashi, M.D, PhD , Hematology, Nagano Red Cross Hospital, Nagano, Japan
Presentation recording not available for download or distribution as requested by the presenting author.
Background: Tacrolimus (TAC) effectively and selectively suppresses T lymphocyte activity, and is used for GVHD prophylaxis. According to some reports, pre-engraftment immune reactions (PIR) occur early after CBT. During PIR phase, we often experience instability of blood concentration of TAC, and need the dose of the drug adjusted accordingly. There are no reports assessing changes in TAC concentration during the PIR phase.

Patients and Methods: Between July 2003 and November 2013, 105 patients received single-unit cord blood transplantation (CBT) at our institution. We analyzed data for 63 patients for whom only TAC was used for GVHD prophylaxis. The conditioning regimen was myeloablative conditioning regimen for 11 patients and reduced intensity conditioning for 52 patients. We assumed that the blood concentration of TAC would reach a steady state between days 5 to 7 and would be proportional to the dose used. Thus, the average concentration of days 5 to 7 was used as the reference value. TAC dose was adjusted based on blood concentration and patient body weight, and compared with the reference dose until day 40. PIR was diagnosed based on the criteria set forth by Wake et al.

Results: Engraftment was achieved in 59 patients (median, day 25), and 46 developed PIR. The blood concentration of TAC significantly decreased in the PIR group on day 8 (P < 0.001), but not in non-PIR group. On days 8, 9, and 10, the adjusted dose of TAC significantly increased in the PIR group (P<0.001, 0.001, and 0.003, respectively) corresponding to the decreased blood concentration of TAC, but not in the non-PIR group.

Conclusions: Decreased blood concentration of TAC and increased requirement of TAC dose in the PIR phase were observed. During the PIR phase, frequent check of the TAC blood concentration and adjustment of the drug should be performed. These phenomena are possibly associated with T lymphocyte activation.

Disclosures:
Nothing To Disclose