Implementation and evaluation of high-dose methotrexate administration guidelines.

BACKGROUND: High-dose methotrexate is used to treat a variety of malignancies. Methotrexate-associated supportive care and the threshold methotrexate level for the discontinuation of supportive care are not consistent among studies. We evaluated the implementation of high-dose methotrexate administration guidelines, which raised the standard threshold methotrexate level for the discontinuation of supportive care from <0.05 to <0.1 µmol. METHODS: A single-center, observational analysis of patients receiving high-dose methotrexate from 1 January 2015 to 31 May 2017 was conducted. The primary endpoint was time from the start of the methotrexate infusion until the discontinuation of the sodium bicarbonate infusion, before and after guideline implementation. RESULTS: Fifty-two patients met the inclusion criteria, which comprised of a total of 136 individual methotrexate doses and were included in the retrospective analysis. Twenty-four patients were included in the prospective analysis, which comprised a total of 46 individual methotrexate doses. The primary endpoint, time until discontinuation of the sodium bicarbonate infusion, was a median of 97.7 h in the retrospective group versus 73.2 h in the prospective group (p = 0.098). Secondary endpoints also favored patients in the prospective group, including hours of hospitalization, number of methotrexate levels checked, weight gained during admission, and adherence to the guideline. CONCLUSION: Among patients who received high-dose methotrexate, implementation of a guideline using a methotrexate threshold of <0.1 µmol was able to significantly decrease the time to discontinuation of supportive care and subsequently may lead to early hospital discharge given that we did not show a statistical significance.

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia.

Treatment options for chronic lymphocytic leukemia, the most common leukemia in the United States, have expanded rapidly in recent years. While traditional chemoimmunotherapy still remains a mainstay for young, fit patients, a number of novel targeted therapies have emerged that have changed the therapeutic landscape. Two innovative anti-CD20 monoclonal antibodies, obinutuzumab and ofatumomamab, have demonstrated activity in chronic lymphocytic leukemia and represent well-tolerated options in upfront management of elderly patients or in those with significant comorbidities. Agents targeting the B-cell receptor pathway, ibrutinib and idelalisib, have excellent activity in chronic lymphocytic leukemia, particularly in those patients with 17p deletions, in which responses to chemoimmunotherapy are traditionally dismal. Venetoclax (ABT-199), the recently FDA-approved BCL2 inhibitor, as well as several other agents and therapy combinations in the pipeline offer great promise for patients with chronic lymphocytic leukemia, particularly in the relapsed/refractory setting. This article comprehensively reviews the data for novel agents in chronic lymphocytic leukemia, including the pharmacology of therapies, unique toxicities, and other practical management considerations for clinicians.