Acute lymphocytic leukemia in a patient with long-term carbamazepine exposure: Acute lymphoblastic leukemia that develops in a patient who has been using carbamazepine for a long time

Introduction

Carbamazepine inhibits action potential formation by blocking the presynaptic voltage-dependent sodium channel. It is metabolized by CYP3A4. It is transformed into 10–11 epoxide and excreted in the urine. It is used in the treatment of partial and generalized epilepsies, bipolar disorder, trigeminal neuralgia, postherpetic neuralgia, and phantom limb pain. We wanted to present our case, in which we think acute lymphoblastic leukemia (ALL) developed due to the long-term use of carbamazepine, which has hematological side effects such as thrombocytopenia, agranulocytosis, neutropenia, and anemia.

Case report

Sixty-five (65) years old male patient presented with complaints of weakness and fatigue in the last 2 months. In his history, he had been using carbamazepine 3 × 200 mg due to epilepsy since the age of 37. There was no other known illness or chronic drug use. On physical examination, he was pale and there was no lymphadenopathy. In his laboratory; WBC: 12 × 10³ (3.5–10.5), Hb: 4.7 g/dL (13.5–17.5), and PLT: 11 × 10³ (150–450). Neutrophils and thrombocytes were decreased in the peripheral smear, and 70% of the lymphocytes were large blastic cells. Bone marrow aspiration; infiltration with large blastic cells (narrow cytoplasm, hyperchromatic nucleus) was observed (Figure 1). CD19(+), CD10(+), HLADR(+), CD34(+), CD21(+), CD22(+), TdT(+), and cytoplasmic CD79a (+) were monitored by flow cytometry. These findings were consistent with CALLA(+) pre B ALL. The carbamazepine treatment that the patient was using was discontinued and standard chemotherapy was started for ALL (CALGB protocol). Levetiracetam was started for epilepsy.

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Figure 1.

Bone marrow infiltrated with blastic cells (narrow cytoplasm, hyperchromatic nucleus).

Discussion

Carbamazepine is an antiepileptic drug used in the treatment of epilepsy, trigeminal neuralgia, and bipolar disorder. It blocks sodium channels and also prevents serotonin reuptake. Although carbamazepine is widely used in the treatment of many medical conditions, it has many side effects such as liver failure, cholestatic jaundice, kidney failure, polyuria, albuminuria, dizziness, headache, drowsiness, hallucinations, nausea, vomiting, abdominal pain, heart failure, and increased blood pressure shows effect. Hematological effects that may develop with this anticonvulsant; agranulocytosis, thrombocytopenia, leukopenia, aplastic anemia, eosinophilia, or pancytopenia.^1–3 Our patient had neutropenia, anemia, and thrombocytopenia.

Carbamazepine is widely used in the treatment of epilepsy, it contributes to many hematological disorders. Carbamazepine can cause acute lymphoblastic leukemia, ⁴ CD30 (+) pseudolymphoma,^5,6 and DRESS syndrome.^7,8 We diagnosed our patient with carbamazepine-associated ALL. Although all of these side effects are described very rarely and some only appear as case reports, they still pose a threat to the health and life of patients chronically treated with this drug. Most of the mechanisms of carbamazepine in the development of these hematological abnormalities are not clear. More research and analysis is needed.

It was stated that carbamazepine treatment should be discontinued if the WBC value is less than 3 × 10³, the platelet level is less than 100 × 10³, and the neutrophil count is less than 1.5 × 10³. ³

In conclusion, the hematological side effects of carbamazepine, although uncommon, should be kept in mind because of their serious, long-term, and sometimes fatal consequences. At the beginning of treatment, it is necessary to explain the possible side effects of carbamazepine to patients and advise patients to have their blood counts monitored regularly.

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