Conference Coverage

Intrathecal methotrexate dosing in acute leukemia falls short



– Although intrathecal chemoprophylaxis for prevention of central nervous system involvement is an essential component of modern regimens to treat acute lymphoblastic leukemia (ALL), patients don’t always receive the recommended number of doses, potentially compromising remissions.

Dr. Sven A. Sommerfeld of Christie Hospital in Manchester, England Neil Osterweil/MDedge News

Dr. Sven A. Sommerfeld

But as a large-scale audit of health care delivery in the United Kingdom has suggested, many of the possible causes for suboptimal delivery of intrathecal methotrexate (IT MTX) appear to be modifiable, reported Sven A. Sommerfeld, MD, and his colleagues from the Christie Hospital in Manchester, England.

“In our clinical observations, and confirmed in this audit, patients on intensive chemotherapy, including induction and consolidation protocols for acute lymphoblastic leukemia, can develop a number of issues and toxicities, which can interfere with the administration of IT MTX,” they wrote in a poster presented at the annual congress of the European Hematology Association.

Reasons for canceling or postponing scheduled doses of IT MTX range from “fairly compelling clinical reasons affecting patient safety or tolerance” to more mundane issues, such as scheduling and staffing problems, the investigators found.

“I think there are a number of factors that can improve compliance, including having your cancellation rate as low as possible. You have already prescribed the treatment, the patient is supposed to be attending [clinic], yet for some reason you cannot go ahead,” Dr. Sommerfeld said in an interview. “I think blood product support is important, but there are capacity issues. Organization of complex treatment protocols that involve systemic chemotherapy and concurrent intrathecal administration can be difficult as different people oversee both of these treatments.”

For example, protocols specify delivery of intrathecal chemoprophylaxis on specific days and induction chemotherapy on other days, and it may be difficult to coordinate the care so that the doses don’t overlap, he said.

Dr. Sommerfeld and his colleagues conducted an audit of standard of care for patients aged 16-60 years who were diagnosed with B-cell or T-cell ALL and received IT MTX under one of two clinical protocols: UKALL 2011 or UKALL 14.

The investigators examined data on IT MTX compliance and assigned each patient a compliance score calculated by the number of administered doses divided by protocol-defined number of doses. They also examined pharmacy records of cancellations of protocol-scheduled IT MTX from January 2016 through July 2017.

They found that the total number of IT MTX prescriptions delivered as a proportion of the number prescribed ranged from a low of 61.8% in 2009 to a high of 84.2% in 2007.

When the investigators looked at records for individual patients, including 29 adolescent and young adults receiving IT MTX under the UKALL 2011 protocol and 27 adults receiving it under the UKALL 14 protocol, they found that failure to maintain coagulation levels within parameters accounted for 23% of cancellations. The next most common reasons for cancellation were rescheduling for administrative or clinical reasons in 20% of canceled doses, low platelet levels in 19% of cases, and patient nonattendance or communication failure in 16% of cases. Other factors included problems with lumbar access, vincristine schedule for the same day, recent anticoagulation, and delay of blood results.

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