Immunotherapy-associated autoimmune hemolytic anemia induced by anti-PD-1 therapy in esophageal cancer: A case report and literature review

Abstract

Rationale: Numerous immune checkpoint inhibitors have been approved for clinical use in metastatic advanced esophageal cancer. While immunotherapy brings therapeutic benefits, immune-related adverse events (irAEs) should nevertheless not be overlooked. This paper reports on the first documented case of Autoimmune hemolytic anemia (AIHA) caused by anti-programmed cell death protein-1 therapy in esophageal squamous cancer.

Patient concerns: An 84-year-old female patient with metastatic squamous esophageal cancer developed chest tightness, generalized weakness, and a yellowing of the skin after 2 cycles of sintilimab treatment.

Diagnoses: Initial examination revealed severe anemia with elevated levels of bilirubin, reticulocytes, lactate dehydrogenase, decreased levels of haptoglobin, and a positive direct antihuman globulin test. The patient was diagnosed with immunotherapy-associated AIHA.

Interventions: The patient was promptly treated with corticosteroids and human immunoglobulin, supportive transfusion with washed erythrocytes.

Outcomes: Her AIHA was controlled after treatment. Subsequent immunotherapy was not continued, and there was no recurrence of AIHA.

Lessons: We have identified a rare case of serious adverse reaction caused by anti-PD-1 therapy. We summarize the clinical presentations, diagnosis, and treatment of this case of immunotherapy-related AIHA and discuss the pathogenesis and therapeutic advances in immunotherapy-related AIHA, as well as sintilimab-induced irAEs, in detail. These findings underscore the importance of the early detection, diagnosis, and treatment of these rare and potentially fatal irAEs.

Keywords: autoimmune hemolytic anemia; case report; esophageal cancer; immunotherapy; sintilimab.

Figure 1.

Bone marrow and imaging findings of the patient. (A) Bone marrow smear findings of marked erythroid hyperplasia (the erythroblasts marked by the red arrows). (B) Bone marrow biopsy findings of moderately active bone marrow erythroid hyperplasia (the area marked by the red arrows). (C) Imaging findings indicative of a moderate amount of bilateral pleural effusion.

Figure 2.

Dynamic hematology tests during the treatment period. (A) Hemoglobin (g/L). (B) Lactate dehydrogenase (U/L). (C) Red blood cell count (×10¹²/L). (D) Bilirubin (μmol/L). (E) Platelets (×10⁹/L). (F) White cell count (×10⁹/L).