Autoantibody Inhibitor Eradication In Acquired Hemophilia Associated with Cancer: a Retrospective Analysis.

Acquired hemophilia (AH), a rare autoimmune disorder primarily of adults, is typically characterized by the presence of IgG oligoclonal antibodies to the clotting factor VIII protein (FVIII). About 10–15% of patients with AH have an underlying malignancy, but the etiologic relationship of cancer to formation of FVIII inhibitor is yet to be determined. To date, there have been no published, comprehensive reviews on the efficacy of various treatments for AH in the context of either solid tumor or hematologic malignancies. Therefore, we have systematically reviewed 86 patients with cancer-associated AH from our own cancer center and from the published literature.

The literature search for this systematic review was performed using PubMed MEDLINE, Ovid MEDLINE, CINAHL, SCOPUS, and Embase. The search terms included various combinations of “acquired”, “cancer”, “factor VIII”, “hemophilia A”, “autoantibodies”, and “treatment.” The major criterion for inclusion was a diagnosis of cancer before or within three months after appearance of acquired inhibitor. Both solid and hematologic malignancies were included. Any report that did not document a FVIII inhibitor titer and/or FVIII activity was excluded. Success in inhibitor eradication has been defined as undetectable inhibitor and normalization of FVIII activity. All articles with an abstract in English published in the period from January 1985 to July 2010 were considered.

86 cases of AH were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age is 67.8 years. 74% of patients were of Caucasian or European background, 8% were of Asian descent, and 2% were of African descent. AH was associated with solid malignancy in 50 cases (58%) and hematologic malignancy in 36 cases (42%). Among all AH cases, 15% and 14% of patients had lymphoma and CLL, respectively. Of the solid tumors, lung and prostate carcinoma (each 12%) occurred with the greatest frequency followed by colorectal (9%) and bladder (5%).

Not all patients had treatment for their underlying cancer, bleeding and/or inhibitor. Complete eradication (CE) of inhibitor was achieved in 48 patients (56%), no eradication (NE) in 22 (26%), and 16 (18%) had unknown status. Of the 73% of patients with CE, 22 were treated with chemotherapy, 10 were treated with surgery, and 1 with both (Table 1). In this series, there was a trend towards successful inhibitor eradication with treatment of B-cell lymphoproliferative malignancies as well as lung and prostate cancer. Long term survival was best achieved when successful CE and treatment of underlying malignancy occurred concurrently.

This literature and case series suggests that AH is associated almost equally with hematological and solid tumor malignancies. These retrospective data suggest that treatment of the cancer with chemotherapy or surgery is very likely to induce eradication of the autoantibody inhibitor. There is a trend for increased success in CE in B-cell lymphoproliferative malignancies and selected solid tumors. Long term survival appears dependent on concurrent CE and treatment of the cancer.

Kessler:Grifols S.A.: Research Funding; Baxter-Immuno: Research Funding; NovoNordisk: Research Funding.