Autoimmune complications following purine analog therapy
- Jeffrey Zonder, MD
Jeffrey Zonder, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
Purine analogs have long been an important part of the treatment of hematologic malignancies. The adenosine analogue fludarabine remains perhaps the most widely used agent to treat chronic lymphocytic leukemia (CLL). Multiple cases of autoimmune hemolytic anemia (AIHA) [1-5] as well as autoimmune thrombocytopenia [6-10], apparently triggered by treatment with fludarabine treatment, have been reported.
Autoimmune hemolytic anemia and immune thrombocytopenia (ITP) following the use of purine analogs (ie, fludarabine, cladribine, pentostatin) will be reviewed here. Infectious complications following purine analog therapy are discussed separately. (See "Risk of infections in patients with chronic lymphocytic leukemia", section on 'Purine analogs'.)
The clinical features, pathogenesis, diagnosis, and treatment of de novo autoimmune hemolytic anemia and de novo immune thrombocytopenia (ITP) are discussed separately. (See "Warm autoimmune hemolytic anemia: Clinical features and diagnosis" and "Pathogenesis of autoimmune hemolytic anemia: Warm agglutinins and drugs" and "Warm autoimmune hemolytic anemia: Treatment" and "Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis" and "Immune thrombocytopenia (ITP) in adults: Initial treatment and prognosis".)
AUTOIMMUNITY IN CLL
As many as one-third of patients with chronic lymphocytic leukemia (CLL) may develop AIHA over the course of their illness unrelated to treatment modality , although most series suggest a rate in the range of 4 to 10 percent [12,13]. This background incidence of AIHA, particularly in patients with advanced stage CLL , makes the frequency of AIHA caused by fludarabine difficult to estimate. (See "Clinical presentation, pathologic features, diagnosis, and differential diagnosis of chronic lymphocytic leukemia", section on 'Laboratory abnormalities'.)
Patients with CLL also have an increased incidence of immune-mediated (autoimmune) thrombocytopenia (AITP). The exact incidence of AITP in CLL is unknown, but it is thought to be somewhat lower than that of AIHA .
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- AUTOIMMUNITY IN CLL
- AUTOIMMUNE HEMOLYTIC ANEMIA
- AIHA after fludarabine
- AIHA after cladribine or pentostatin
- Risk factors
- - Development of a positive Coombs test
- - Prior episode of FA-AIHA
- TREATMENT OF FA-AIHA
- Initial steps
- Poorly responsive disease
- - Immunosuppression
- - Chemotherapy
- - Cladribine
- - Rituximab
- - Alemtuzumab
- - Ibrutinib
- - Intravenous immune globulin
- Retreatment with fludarabine or other chemotherapy
- AUTOIMMUNE THROMBOCYTOPENIA
- AUTOIMMUNE NEUTROPENIA
- SUMMARY AND RECOMMENDATIONS