Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

[A case of catheter-related bacteremia of Tsukamurella pulmonis].

Tsukamurella pulmonis is an aerobic actinomycete. We report a catheter-related bacteremia of T. pulmonis. A 39 yr-old male with ALL was hospitalized to receive bone marrow transplantation (BMT). Although the patient developed a high fever at the 7th hospital day (HD), it subsided with vancomycin treatment, and he received BMT at 9th HD. Fever resurged at 16th HD despite sustained treatment with vancomycin, meropenem, and amphotericin B, but subsided with removal of Hickman catheter (HC) at 19th HD. Three sets of blood cultures comprising one from the HC and two from venipunctures were taken at 7th, 16th, and 19th HD, and the distal tip of the HC was also cultured. The aerobic vials of all 3 HC-withdrawn blood cultures and one peripheral blood culture taken at 19HD and the HC tip culture grew long, straight, thin gram-positive rods that were positive on modified Kinyoun stain. This organism showed tiny, rough, grey colonies after 3-day incubation and grew to large flat colonies when incubation was extended. It was catalase-positive, urease-positive, and alkaline-slant/alkaline-deep on triple sugar iron agar, and hydrolyzed hypoxanthine. The sequence of 1,296 base pairs of 16S rRNA of this organism showed a 100.0% homology with the published sequence of T. pulmonis DSM 44142T. To our knowledge, this is the first report of T. pulmonis bacteremia in Korea.

Inverse Tendency between Ex Vivo Expansion Potential of Hematopoietic Progenitors and Time to Engraftment after Hematopoietic Stem Cell Transplantation.

BACKGROUND: The CD34(+) cell dose and infused number of committed progenitor cells in transplantation are important factors in hematologic engraftment. However, the relationship between expansion potential of progenitor cells and hematologic engraftment remains controversial. We evaluated whether expansion potential of progenitor cells is a predictive factor of post-transplantation hematologic engraftment. METHODS: Mononuclear cells isolated from mobilized peripheral blood and bone marrow were cultured with cytokine cocktail for 7 days. Progenitor cells and committed progenitors were analyzed using stem cell markers (CD34 and CD133) and lineage specific markers. Hematologic engraftment was defined as neutrophil counts over 500/microL and platelet counts over 20,000/microL without transfusion. Acute and chronic graft-versus-host disease (GVHD) were investigated. RESULTS: There was inverse tendency between the number and fold expansion of progenitor cells or committed (granulocytic or megakaryocytic) progenitors and time to engraftment. Especially, fold expansion of CD34(+)/CD33(+) cells was significantly correlated with time to neutrophil engraftment in bone marrow transplantation (r=-0.56, P=0.04). The infused number and fold expansion of lymphoid progenitors were not related to the occurrence of acute or chronic GVHD. CONCLUSIONS: We could not prove that expansion potential of progenitor cells and committed progenitor cells is correlated to hematologic engraftment although there is a correlation between CD34(+)/ CD33(+) cells and time to neutrophil engraftment. But, a further study on the value of expansion potential is required because there is an inverse tendency.