Effect of Keratinocyte Growth Factor on Hospital Readmission and Regimen-Related Toxicities after Autologous Hematopoietic Cell Transplantation for Lymphoma.

Regimen-related toxicities with high-dose therapy followed by hematopoietic cell rescue leads to considerable patient distress, morbidity, and high readmission rates. Palifermin is a recombinant keratinocyte growth factor that is Food and Drug Administration-approved to decrease severe oral mucositis (OM) associated with autologous hematopoietic cell transplantation (ASCT) for hematologic malignancies. We added palifermin as a supportive care measure for patients with lymphoma undergoing ASCT with BEAM conditioning. We compared patients receiving palifermin (n = 35) with historical controls (n = 38) for toxicity and readmission outcomes. The cumulative incidence of OM of any grade was 23% in the palifermin-treated patients and 42% in the control group. Patients receiving palifermin were less likely to be readmitted (57% versus 82%; P = .04), had fewer hospital readmission days (median, 4 days versus 7 days; P < .01), and had fewer total days in the hospital through day +30 after ASCT (median, 12 days versus 15 days; P = .05). Fewer patients in the palifermin group had >20 days in the hospital through day +30 (9% in the palifermin group versus 23% of controls). Adverse events associated with palifermin were mild and transient. The addition of palifermin limits severe regimen-related toxicities and decreases readmissions and duration of hospital stay. This and other measures are needed to identify comprehensive and cost-effective approaches, possibly including palifermin, to prevent severe regimen-related toxicities and decrease health care resource utilization.

Sirolimus and mirabegron interaction in a hematopoietic cell transplant patient.

PURPOSE: Hematopoietic cell transplant patients are exposed to numerous classes of medications. Transplant practitioners must vigilantly monitor for drug interactions especially involving immunosuppressants. We report a hematopoietic cell transplant patient receiving sirolimus who developed supratherapeutic serum concentrations after initiating mirabegron. SUMMARY: A 31-year-old, 98 kg female received a second umbilical cord blood transplant four years after the first transplant for relapsed acute myeloid leukemia. Mycophenolate mofetil and sirolimus were utilized for graft versus host disease prophylaxis. The patient was receiving sirolimus 2 mg daily and the serum concentration on day 26 post-transplant (day + 26) was within therapeutic range (6.7 µg/L, goal range 3-12 µg/L). Her post-transplant course was complicated by BK viruria-associated cystitis for which she was started on mirabegron. Six days after starting the new medication (day + 33), the sirolimus serum concentration increased to 19.2 µg/L. Thus mirabegron was discontinued and sirolimus was held. Sirolimus was restarted once the serum concentration was within goal and subsequently stabilized with a combination of 1 mg and 2 mg daily for a total weekly dose of 10 mg. The proposed mechanisms of interaction include: (1) sirolimus inhibition of organic anion transporting polypeptide leading to increased mirabegron in the intestinal lumen; (2) mirabegron inhibition of P-glycoprotein leading to increased absorption of sirolimus and; (3) increased sirolimus absorption leading to increased sirolimus serum concentrations. CONCLUSION: To our knowledge, this is the first report of a potential drug interaction between sirolimus and mirabegron. Transplant specialists should be aware of this potential interaction when considering the concurrent use of these medications.

Glycerol monolaurate and dodecylglycerol effects on Staphylococcus aureus and toxic shock syndrome toxin-1 in vitro and in vivo.

BACKGROUND: Glycerol monolaurate (GML), a 12 carbon fatty acid monoester, inhibits Staphylococcus aureus growth and exotoxin production, but is degraded by S. aureus lipase. Therefore, dodecylglycerol (DDG), a 12 carbon fatty acid monoether, was compared in vitro and in vivo to GML for its effects on S. aureus growth, exotoxin production, and stability. METHODOLOGY/PRINCIPAL FINDINGS: Antimicrobial effects of GML and DDG (0 to 500 microg/ml) on 54 clinical isolates of S. aureus, including pulsed-field gel electrophoresis (PFGE) types USA200, USA300, and USA400, were determined in vitro. A rabbit Wiffle ball infection model assessed GML and DDG (1 mg/ml instilled into the Wiffle ball every other day) effects on S. aureus (MN8) growth (inoculum 3x10(8) CFU/ml), toxic shock syndrome toxin-1 (TSST-1) production, tumor necrosis factor-alpha (TNF-alpha) concentrations and mortality over 7 days. DDG (50 and 100 microg/ml) inhibited S. aureus growth in vitro more effectively than GML (p<0.01) and was stable to lipase degradation. Unlike GML, DDG inhibition of TSST-1 was dependent on S. aureus growth. GML-treated (4 of 5; 80%) and DDG-treated rabbits (2 of 5; 40%) survived after 7 days. Control rabbits (5 of 5; 100%) succumbed by day 4. GML suppressed TNF-alpha at the infection site on day 7; however, DDG did not (<10 ng/ml versus 80 ng/ml, respectively). CONCLUSIONS/SIGNIFICANCE: These data suggest that DDG was stable to S. aureus lipase and inhibited S. aureus growth at lower concentrations than GML in vitro. However, in vivo GML was more effective than DDG by reducing mortality, and suppressing TNF-alpha, S. aureus growth and exotoxin production, which may reduce toxic shock syndrome. GML is proposed as a more effective anti-staphylococcal topical anti-infective candidate than DDG, despite its potential degradation by S. aureus lipase.