Paroxysmal nocturnal hemoglobinuria (PNH) cells are present in the majority of patients with myelodysplastic syndromes (MDS), aplastic anemia (AA), and other bone marrow failure syndromes (BMF), according to interim results from 5,285 patients enrolled in the EXPLORE trial. EXPLORE (EXamination of PNH, by Level Of CD59 on REd and white blood cells) is the first large multicenter study to determine the frequency of PNH cells in these patient populations using a central laboratory conducting a high sensitivity test for PNH cells. The findings from EXPLORE will be presented tomorrow at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO). The EXPLORE trial was sponsored by Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN).

PNH cells are defined as blood stem cells lacking certain proteins, known as GPI-anchored proteins, which include proteins that ordinarily protect blood cells from destruction by complement, a component of the normal immune system. The lack of these complement inhibitors results in the hemolysis (red blood cell destruction) that characterizes PNH, an ultra-rare, debilitating and life-threatening disease.

"The true prevalence of PNH cells in patients with a number of bone marrow failure syndromes has been unclear due to variability in PNH testing. Interim results from the EXPLORE trial show that PNH cells are common in these patients," said Azra Raza, M.D., Director, MDS Program, St. Vincent's Comprehensive Cancer Center, New York. "These results show that high sensitivity testing may help physicians detect undiagnosed PNH in patients with bone marrow failure disorders, and identify those patients with bone marrow failure who may be more likely to respond to immunosuppressive therapy."

Interim results from the EXPLORE trial are based on 5,285 patients with evidence of bone marrow failure, including 4,433 with MDS, 451 with AA, and 351 with other bone marrow failure syndromes (including patients with more than one diagnosis). To eliminate variability in the detection and reporting of PNH cell populations, a central laboratory employed a commercially available high-sensitivity flow cytometry test to identify GPI anchor-deficient PNH red blood cells and white blood cells, resulting in 0.01% sensitivity. Interim results are as follows:

- PNH cells were present in 70% of patients with AA, 55% of patients with MDS, and 55% of patients with other BMF syndromes when tested at a sensitivity of 0.01% PNH cells.

- PNH clones of clinical significance (≥1% of white blood cells) were found in 25% of patients with AA (113 of 451), 1% of patients with MDS (54 of 4,433) and 5% of patients with other BMF syndromes (16 of 351).

- Among patients with PNH clones of clinical significance, elevated levels of hemolysis, or red blood cell destruction, were evident in 38% of patients with AA, 44% of patients with MDS, and 69% of patients with other BMF syndromes. In PNH, excessive hemolysis can lead to thrombosis, pulmonary hypertension, kidney failure, pain and fatigue in affected patients.

- Most patients who tested positive had smaller populations of PNH cells (< 1% of white blood cells), demonstrating the need to test patients using flow cytometry with sufficiently high sensitivity capable of detecting these abnormal cells.

- PNH cells were identified in patients with all subtypes of MDS as well as in patients with both severe and non-severe aplastic anemia, supporting the clinical importance of testing all MDS and AA patients.