Treatment of Central Nervous System Relapse in Acute Promyelocytic Leukemia by Venetoclax: A Case Report.

Xuzhao Zhang,Yanbin Tan,Wenbin Qian,Xian Li,Jinliang Chen,Xiaohong Zhang,Weiqin Wang

doi:10.3389/fonc.2021.693670

Abstract

Extramedullary relapse of acute promyelocytic leukemia is a rare phenomenon and is associated with a poor prognosis, with the central nervous system being the most common site of relapse. The current treatments are still limited. Venetoclax, a selective inhibitor of BCL2, is a small molecule that can cross the blood-brain barrier and shows a potential efficacy in the treatment of chronic lymphocytic leukemia with central nervous system involvement. Although venetoclax has also been used in the treatment of acute myeloid leukemia in recent years, there are no reports of its use in the treatment of central nervous system relapse in acute promyelocytic leukemia. Here, we report a case of central nervous system relapse in acute promyelocytic leukemia that achieved complete remission after oral treatment with venetoclax. The presence of venetoclax in the patient’s CSF was confirmed by testing CSF and plasma by mass spectrometry. The concentration of venetoclax in CSF was approximately 1/300 of that in plasma trough concentration. The treatment experience in this case demonstrates the potential ability of venetoclax to treat of central nervous system relapse/involvement in acute promyelocytic leukemia, thus providing a new treatment option for this kind of patient.

Highlights

Since the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), there have been extraordinary advances in the efficacy of APL treatment [1,2,3,4]
Venetoclax has been used in the treatment of acute myeloid leukemia (AML) in recent years [9, 10], there are no reports of its use in the treatment of central nervous system (CNS) relapse in APL
CNS relapse is a low incidence event in APL but is a factor significantly associated with poor prognosis

Summary

INTRODUCTION

Since the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), there have been extraordinary advances in the efficacy of APL treatment [1,2,3,4]. The patient was treated with methotrexate, cytarabine and dexamethasone twice weekly intrathecal injections in combination with ATO and mannitol continuous intravenous alternating therapy for 30 days and the PML-RARa fusion gene was negative both in the CSF and bone marrow. After taking venetoclax for two weeks while continuing triple IT therapy, the patient’s head swelling was miraculously relieved, and a repeat lumbar puncture four weeks later showed complete disappearance of CSF leukemia cells and immunological remission of the bone marrow was maintained (Figure 2). The concentration of venetoclax in CSF was approximately 1/300 of that in the plasma trough concentration (Figure 3) This patient is still on ongoing venetoclax therapy and has maintained complete remission of CNS for 8 months (Figure 2). To the best of our knowledge, this is the first case of venetoclax applied to CNS relapse of APL

DISCUSSION

Findings

ETHICS STATEMENT