Effect of Linozolid Administration on Myeloid Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation

Background:Linezolid is effective against drug-resistant Gram-positive bacteria, and has been widely used for the treatment of various infectious diseases due to such bacteria. Although linezolid has a favorable safety profile, myelosuppression is one of its clinically important toxicities. Myelosuppression due to linezolid has not been systematically evaluated in the setting of hematopoietic stem cell transplantation (HSCT). Therefore, effect of linezolid administration on the myeloid engraftment after allogeneic HSCT was retrospectively evaluated.

Patients and methods:Patients in whom intravenous or oral linezolid (1200 mg/day) administration was initiated before myeloid engraftment following allogeneic HSCT and continued for 5 days or longer were selected from the institutional database. The patient characteristics, duration of linezolid treatment, and myeloid engraftment were retrospectively evaluated by using the medical records.

Patients and methods: Patients in whom intravenous or oral linezolid (1200 mg/day) administration was initiated before myeloid engraftment following allogeneic HSCT and continued for 5 days or longer were selected from the institutional database. The patient characteristics, duration of linezolid treatment, and myeloid engraftment were retrospectively evaluated by using the medical records.

Results: Fifteen patients were evaluable and enrolled into the analysis. All patients were male, and median age at transplant was 50 years (range, 21 – 60). Underlying diseases were acute leukemia in 11 patients, myelodysplastic syndrome in 2, and myeloproliferative neoplasm and malignant lymphoma each in 1. All but 1 received myeloablative conditioning. Stem cell sources were bone marrow from related or unrelated donor in 10 patients, cord blood in 3, and peripheral blood stem cell (PBSC) in 2. Linezolid was initiated at a median of 12.5 days after HSCT (range, -3 – 20), whose median duration of treatment was 14 days (range, 5 – 20). Although all patients achieved myeloid engraftment (absolute neutrophil exceeding 0.5 x 10⁹/L), the median day of engraftment was 22.5 days after HSCT (range, 12 – 33). Japanese national registry data showed that the median days of myeloid engraftment were 12 days and 14 days after allogeneic PBSCT and BMT, respectively (Nagafuji K, et al. Int J Hematol 2010). In 8 (53%) of 15 patients, myeloid engraftment was achieved later than 21 days after engraftment.

Conclusion: Although myeloid engraftment was achieved, the engraftment was considered delayed in patients who received linezolid early after allogeneic HSCT. Although the number of subjects evaluated was small, these results suggest that linezolid could have a potential to delay neutrophil recovery, and should be carefully used after allogeneic HSCT.