Blast crisis

Last reviewed: March 2019

Last updated: December 2018

07 Dec 2018

Reversible posterior leukoencephalopathy syndrome in patients receiving ponatinib

Healthcare professionals are advised that there is a risk of reversible posterior leukoencephalopathy syndrome (RPLS, also known as posterior reversible encephalopathy syndrome) in patients taking ponatinib.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has advised that:

A routine European review suggests that the risk could affect up to 1 in 100 people who are taking the medicine.
Treatment should be interrupted if RPLS is confirmed, and resumed only when it has resolved and if the benefits of continuing treatment outweigh the risk of RPLS.
Patients receiving ponatinib should be advised to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes.

RPLS is a neurologic disorder that can present with seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurologic disturbances.

The MHRA advice follows a European post-marketing review of ponatinib that identified five cases of RPLS; two cases improved after treatment withdrawal, and did not reappear when restarted at a lower dose. RPLS is included in the warnings/precautions section of the US prescribing information.

Ponatinib (a tyrosine kinase inhibitor) is indicated for adults with chronic-phase, accelerated-phase, or blast-phase chronic myelogenous leukemia who are resistant or unsuitable for treatment with other tyrosine kinase inhibitors, or who have the T315I mutation.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Blast phase of chronic myelogenous leukemia (CML), which can be discovered incidentally on CBC or in assessment of patients with symptoms and signs such as fever, fatigue, weight loss, anemia, thrombocytopenia, or splenomegaly.

Diagnosis of CML requires presence of a Philadelphia chromosome gene mutation. Diagnosis of the blast phase of CML is based on percentage of blasts in peripheral smear or bone marrow.

Tyrosine kinase inhibitors are paramount in treatment. Allogeneic stem cell transplant must follow due to rapid relapse.

Definition

Blast crisis refers to the transformation of chronic myelogenous leukemia (CML) from the chronic or accelerated phase to blast phase. This is characterized by blast cells (≥20% by WHO criteria; ≥30% by MD Anderson Cancer Center and the International Bone Marrow Transplant Registry criteria) in the peripheral blood smear or the bone marrow, or the presence of an extramedullary accumulation of blast cells, or large foci or clusters of blasts in the bone marrow biopsy. [1] [2] CML is characterized by the presence of the Philadelphia chromosome, which results from a reciprocal translocation of chromosomes 9 and 22, juxtaposing the proto-oncogene c-abl from chromosome 9 to the breakpoint cluster region in chromosome 22. [3]