Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease that can lead to life-threatening complications including thrombotic events (TE), chronic kidney disease (CKD) and pulmonary hypertension. An international PNH Registry was implemented in 2008 to enhance understanding of the natural history of PNH, to describe treatment outcomes, and to evaluate the long term safety of eculizumab in treated patients.
This Registry is a non-interventional, prospective, multicenter, observational study. All patients with a diagnosis of PNH (confirmed in accordance with international diagnostic guidelines) or a detected PNH clone are enrolled irrespective of age or therapy. Data on patient demographics, medical histories, disease characteristics and treatment are collected at enrollment, every 6 months thereafter and/or at discontinuation. Descriptive statistics are used to describe the data; n, median and range (min–max) for continuous variables and percentages for categorical parameters.
As of May 1, 2013, the Registry has enrolled 248 patients from Russia, over 50% of whom have a history of aplastic anemia or other bone marrow disorder (BMD) (Table 1). Disease characteristics for the overall population and by clone size or LDH level are presented in table1.A total of 25 patients have received eculizumab and have available follow-up data after starting treatment; median (range) follow-up time 4.4 (0.3–8.3) months. Among the 11 patients treated with eculizumab and with available LDH levels, the median LDH ratio was 5.7 X ULN before treatment and 1.0 X ULN at last follow-up assessment.
Patient and disease characteristics at enrollment
| . | All patients . | Classic hemolytic PNH . | BMD-PNH . | Subclinical PNH . |
|---|---|---|---|---|
| Demographics | ||||
| Total patients, N (%) | 248 (100) | 57 (22.7) | 133 (53.0) | 58 (23.1) |
| Age in years, median (range) | 32 (1–85) | 36 (18–76) | 30 (1–85) | 28 (9–75) |
| Gender female, n (%) | 144 (58.3) | 38 (66.7) | 80 (60.6) | 26 (44.8) |
| Time to diagnosis in months, median (range) | 11 (0–310) | 33 (0–310) | 11 (0–238) | 7 (2–133) |
| Disease characteristics | ||||
| % Granulocyte clones, median | 8.1 | 93.0 | 9.7 | 0.2 |
| LDH ratio x ULN, median | 1.3 | 6.0 | 1.5 | 0.8 |
| History of TE, n (%) | 21 (8.5) | 11 (19.3) | 8 (6.1) | 2 (3.4) |
| Impaired renal function, n (%) | 47 (19.0) | 18 (31.6) | 17 (12.9) | 12 (20.7) |
| Pulmonary hypertension, n (%) | 11 (4.5) | 8 (14.0) | 2 (1.5) | 1 (1.7) |
| Disease characteristics by PNH granulocyte clone size | ||||
| <20% | ≥20% | |||
| Total patients, N | 133 | 105 | ||
| History of TE, n (%) | 2 (1.5) | 16 (15.2) | ||
| Impaired renal function, n (%) | 20 (15.0) | 27 (25.7) | ||
| Pulmonary hypertension, n (%) | 1 (0.8) | 9 (8.6) | ||
| LDH ratio x ULN, median | 0.8 | 4.5 | ||
| Disease characteristics by LDH ratio category | ||||
| <1.5 x ULN | ≥1.5 x ULN | |||
| Total patients, n | 93 | 71 | ||
| History of TE*, n (%) | 1 (1.1) | 10 (14.1) | ||
| Impaired renal function, n (%) | 16 (17.2) | 22 (31.0) | ||
| Pulmonary hypertension, n (%) | 0 | 8 (11.3) | ||
| . | All patients . | Classic hemolytic PNH . | BMD-PNH . | Subclinical PNH . |
|---|---|---|---|---|
| Demographics | ||||
| Total patients, N (%) | 248 (100) | 57 (22.7) | 133 (53.0) | 58 (23.1) |
| Age in years, median (range) | 32 (1–85) | 36 (18–76) | 30 (1–85) | 28 (9–75) |
| Gender female, n (%) | 144 (58.3) | 38 (66.7) | 80 (60.6) | 26 (44.8) |
| Time to diagnosis in months, median (range) | 11 (0–310) | 33 (0–310) | 11 (0–238) | 7 (2–133) |
| Disease characteristics | ||||
| % Granulocyte clones, median | 8.1 | 93.0 | 9.7 | 0.2 |
| LDH ratio x ULN, median | 1.3 | 6.0 | 1.5 | 0.8 |
| History of TE, n (%) | 21 (8.5) | 11 (19.3) | 8 (6.1) | 2 (3.4) |
| Impaired renal function, n (%) | 47 (19.0) | 18 (31.6) | 17 (12.9) | 12 (20.7) |
| Pulmonary hypertension, n (%) | 11 (4.5) | 8 (14.0) | 2 (1.5) | 1 (1.7) |
| Disease characteristics by PNH granulocyte clone size | ||||
| <20% | ≥20% | |||
| Total patients, N | 133 | 105 | ||
| History of TE, n (%) | 2 (1.5) | 16 (15.2) | ||
| Impaired renal function, n (%) | 20 (15.0) | 27 (25.7) | ||
| Pulmonary hypertension, n (%) | 1 (0.8) | 9 (8.6) | ||
| LDH ratio x ULN, median | 0.8 | 4.5 | ||
| Disease characteristics by LDH ratio category | ||||
| <1.5 x ULN | ≥1.5 x ULN | |||
| Total patients, n | 93 | 71 | ||
| History of TE*, n (%) | 1 (1.1) | 10 (14.1) | ||
| Impaired renal function, n (%) | 16 (17.2) | 22 (31.0) | ||
| Pulmonary hypertension, n (%) | 0 | 8 (11.3) | ||
BMD, bone marrow disorder; PNH, Paroxysmal nocturnal hemoglobinuria.
Russian patients included in the International PNH Registry show broad ranges of age, clone size, and degrees of hemolysis. History of TE, impaired renal function, and signs of chronic hemolysis are present among these patients regardless of PNH clone size. History of TE was recorded more frequently in patients with PNH clone sizes ≥20%, and was also more frequent among patients with LDH levels ≥1.5 x ULN. Among patients treated with eculizumab there was a marked decrease in hemolysis (as measured by LDH levels).
Lisukov:Alexion: Honoraria. Kulagin:Alexion: Honoraria. Shilova:Alexion: Honoraria. Afanasyev:Alexion: Honoraria.
Author notes
Asterisk with author names denotes non-ASH members.
