Rory Bennett, Merit Hanna, Rajeev Rajagopal.

A 55 year old female responding to Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed myeloma developed marked progressive macrocytic anaemia, from normal baseline values, over the first three treatment cycles. She remained asymptomatic and experienced no other cytopenia, yet her Hb declined from 121g/L pre-treatment to 88g/L, and MCV increased from 93fL to 107fL, with a reticulocytosis of 163 x 10^9. IgG paraprotein reduced from 16g/l to 4g/l over the same interval.  Haptoglobins were reduced at 0.1g/L; the Coombs test and G6PD screen were both negative. There were no other incriminating oxidant medications.

Blood film examination showed striking numbers of bite cells, polychromatic cells, with occasional helmet, blister and irregularly contracted cells. Heinz bodies were detectable as globular aggregates on fresh and incubated supravital stain preparations. The Romanowsky and brilliant cresyl blue stains demonstrate these respectively.

We have noted similar indices, blood film appearances and positive haemolytic markers indicative of oxidative haemolysis in other patients receiving high dose Carfilzomib-based therapy ¹. It occurs in the absence of confounding medications or known metabolic predisposition to oxidative stress haemolysis.

Learning points:

1. Carfilzomib induces oxidative haemolysis which is likely the main mechanism of therapy-related anaemia. Denatured haemoglobin precipitating as Heinz bodies can be easily detected by incubating the erythrocytes with a supravital stain.

2. Progressive macrocytosis, especially if accompanied by reticulocytosis, should alert the clinician to the possibility of oxidative haemolysis in the responding patients treated with Carfilzomib.

References:

1.      High dose carfilzomib proteasome inhibition induces anemia by oxidative hemolysis: A case series of 8 patients from a single centre. Rajagopal, R. et al. Am J Hematol. 2019; 1–2.