Two cases of marked red cell anisopoikilocytosis and haemolysis with alectinib, an anaplastic lymphoma kinase inhibitor

Abstract

The first patient was a 66-year-old man with brain only metastasis. He had a background of β thalassaemia trait, with a baseline haemoglobin (Hb) concentration of 115 g/l and mean corpuscular volume (MCV) of 62 fl. After 1 month of therapy his Hb had decreased to 80 g/l. Haemolytic markers were abnormal, including unconjugated bilirubin 31 μmol/l, lactate dehydrogenase (LDH) 758 units/l, haptoglobin 0.04 g/l and reticulocyte count 140 × 109/l. A direct anti-globulin test (DAT) was negative. His blood film (left) showed marked fragmentation and marked anisopoikilocytosis, with irregularly contracted cells, acanthocytes, microspherocytes and polychromasia. There was background microcytosis and basophilic stippling, consistent with known β thalassaemia trait. Follow-up at 2 weeks demonstrated persistent morphological changes, but improvements in haemolytic parameters. Alectinib was permanently ceased, with the plan for use of an alternative ALK inhibitor on disease progression. The second patient was a 77-year-old woman with nodal, pulmonary and pleural disease. At 3 months after initiation of alectinib her Hb had decreased from a baseline of 115 to 93 g/l, with evidence of haemolysis including an unconjugated bilirubin peaking at 93 μmol/l, LDH 322 units/l, haptoglobin 0.97 g/l, reticulocyte count 100 × 109/l, and a negative DAT. The film (right) showed marked spheroacanthocytosis. In contrast to the first case, there was minimal red cell fragmentation. At 2 weeks after alectinib cessation, the patient’s unconjugated bilirubin had normalised to 12 μmol/l, and her Hb was stable at 90 g/l. She was re-challenged with a reduced dose of alectinib at 450 mg twice daily (from 600 mg twice daily), with the outcome pending. This report highlights the need for both clinicians and morphologists to be vigilant for unrecognised off-target effects of novel agents, and also the importance of clinicopathological correlation.