Abstract
As an Immune checkpoint blockade therapy (ICB), nivolumab has demonstrated efficacy in Acute Myeloid Leukemia (AML) and various other malignancies. Nivolumab is used as an anti-programmed cell death 1 (PD-1) agent. The toxicities are observed in more than 10% of patients, because of its ability, anti-PD-1 will upregulate the activity of T-cells. Over-activated T-cells will cause immune-related adverse events such as Aplastic Anemia (AA). Here, we present a case of an over 60-years old male patient with AML, and the possibility for him to receive an allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patient was treated with nivolumab and subsequently developed AA. As an additional consideration, we will also discuss whether allo-HSCT is transplantable when AA is performed during the treatment of AML.
Highlights
Acute Myeloid Leukemia (AML) is a type of blood cancer with excess immature white blood cells in bone marrow
AML- associated regulatory T-cells (Tregs) will downregulate the function of adoptively transferred cytotoxic T-cells in vivo, and Tregs depletion followed by programmed cell death 1 (PD-1) inhibitor such as nivolumab will result in a superior anti-AML ability (Sehgal et al 2015) This mechanism of nivolumab in AML is likely to over-activate the T-cells which causes immune-related adverse events such as AA (Comito et al 2017)
Immune-related adverse event AA presenting before allo-HSCT during the nivolumab treatment for AML could be an indication of relapse after HSCT
Summary
AML is a type of blood cancer with excess immature white blood cells in bone marrow. AML- associated regulatory T-cells (Tregs) will downregulate the function of adoptively transferred cytotoxic T-cells in vivo, and Tregs depletion followed by PD-1 inhibitor such as nivolumab will result in a superior anti-AML ability (Sehgal et al 2015) This mechanism of nivolumab in AML is likely to over-activate the T-cells which causes immune-related adverse events such as AA (Comito et al 2017). The patient had diarrhea, dizziness and headache which was most likely caused by chemotherapy, according to the comprehensive review of systems It reveals the patient reported no other adverse reaction besides common side effects of IA regimen from the chemotherapy.On day 8, the first dose of nivolumab (1 mg/kg by vein) was started without induction chemotherapy and continued every two weeks for 10 cycles. As the following 12th dose of nivolumab was served, the patient’s platelet counts gradually dropped to 5×109/L This result may reveal bone marrow damage, and it was possibly attributed to the nivolumab treatment. Due to the development of presumed grade 2/4 drugmediated autoimmune complication, the patient responded well to the steroid therapy In this case, stop administrate nivolumab during the AML treatment, will put patient at high risk for relapse. The patient has reached complete remission, no other adverse reaction is developing and further HSCT should be considered
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