Presenting a rare clinical case of a patient with Aplastic Anemia (AA) developed after treatment with Temozolomide who achieved complete hematologic recovery induced by eltrombopag.

Retrospective descriptive study of a clinical case carried out through data collection from HSPE medical records.

A 32-year-old woman who underwent surgical resection of a low-grade glioma associated with radiotherapy (56 Gy) and chemotherapy with temozolomide (15 mg/day for 30 days) presents with pancytopenia 15 days after the end of chemotherapy. As a consequence of the cytopenias, which were at first attributed to the toxicity of the glioma treatment, the patient had retinal bleeding, metrorrhagia and several hospitalizations due to infection. There was no improvement in cytopenias one year after the onset of the condition, with hemoglobin (Hb) 5,8 g/dL leukocytes (Lt) 1770/mm3 (neutrophils (N) 549, lymphocytes (Ly) 1044) Platelets 8000/mm3, bone marrow biopsy (BMB) revealed 20% hematopoietic tissue, hypocellular in the three sectors, with better representation of the erythroblastic sector, erythroblasts in cohesive clusters, granulocytes with preserved maturation, scarce small and hypolobulated megakaryocytes, and 1% lymphocytosis. Diagnosis of AA was confirmed and eltrombopag 150 mg/day was started as a single therapy. After 8 months the patient presented: Hb 13.8 g/dL Lt 3200/mm3 (N1152 Ly1504) Platelets 154000/mm3, with complete improvement of symptoms. BMB performed 16 months after the introduction of eltrombopag showed 40% of representative hematopoietic tissue in the 3 sectors, compatible with regeneration after bone marrow aplasia. Corticosteroid weaning was performed and eltrombopag was withdrawn with maintenance of hematological response, with no further cytopenias in the blood count. Discussion: It is known that Temozolomide therapy can lead to hematological toxicity, with thrombocytopenia, leukopenia and, more commonly, neutropenia. Myelosuppression, however, is considered dose-dependent and it is usually reversible after drug's suspension in approximately 15 days, it occur in less than 5% of patients. A current study showed that 0.6% of patients who used Temozolomide developed AA, therefore a rare complication. The causality between the therapy used and the development of AA could not be definitively established, however discontinuing treatment after one year did not lead to bone marrow recovery. It is also known that the most frequent mechanism related to acquired AA is an immune-mediated destruction of hematopoietic stem cells (HSCs) and bone marrow progenitor cells. At first, thrombopoietin (TPO) agonists were associated with megakaryocyte stimulation and platelet production. However, in vitro studies also suggest that TPO plays a key role in the proliferation and maintenance of HSCs. In the case presented here, there was complete hematological recovery with the use of eltrombopag, a thrombopoietin agonist.

Despite the safety of Temozolomide and its effectiveness, there are a few cases of myelosuppression and aplastic anemia resulting from its use in the literature, such as the report presented here. The treatment of AA induced by this medication is not well defined, but it was successfully in this report using eltrombopag.