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3341 Different Clinical Characteristics of Paroxysmal Nocturnal Hemoglobinuria in Pediatric and Adult Patients

Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron
Program: Oral and Poster Abstracts
Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Alvaro Urbano-Ispizua1*, Petra Muus, MD, PhD2, Hubert Schrezenmeier, MD3,4,5, Antonio Medina Almeida, MD, PhD6*, Amanda Wilson, MPH, PhD7* and Russell E. Ware, MD, PhD8

1Hematology Department, Institute of Hematology and Oncology, University of Barcelona, Hospital Clínic, Barcelona, Spain
2Radboudumc, Nijmegen, Netherlands
3German Red Cross Blood Transfusion Service Baden-Württemberg–Hessen and Institute of Transfusion Medicine, Ulm, Germany
4German Red Cross Blood Transfusion Service, Baden-Württemberg-Hessen, Germany
5Institute of Transfusion Medicine, University of Ulm, Ulm, Germany
6Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
7Alexion Pharma International, Cambridge, MA
8Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Introduction: Studies of children with paroxysmal nocturnal hemoglobinuria (PNH) are scarce and include a very limited number of patients. The objective of this analysis was to describe characteristics of PNH at enrollment for the largest available registry of pediatric patients, and to compare demographic and clinical characteristics with those of adult patients.

Methods: The International PNH Registry is a prospective, multi-center worldwide, observational study of patients with a PNH clone of 0.01-100%. Data are collected from patient medical records at the time of Registry enrollment and every six months thereafter. Adult patients were ³18 years of age at enrollment and disease start and pediatric patients were <18 years at enrollment. Demographics and clinical parameters in patients untreated with eculizumab at enrollment for the two age cohorts were compared using the Wilcoxon-Mann-Whitney test for medians and PearsonÕs chi-square for frequencies. The rate of thrombotic events (TE) between disease start (defined as the earliest reported PNH symptoms, granulocyte clone, or PNH diagnosis) and enrollment was calculated per 100 person-years.

Results: As of March 2, 2015, a total of 2,184 patients were eligible for analysis: 94 (4.3%) pediatric patients and 2,090 (95.7%) adult patients. Median age (range) at enrollment was 14.0 years (3-17) in pediatrics and 45.5 years (18-100) in adults; median disease duration was 0.7 years and 2.1 years, respectively (p<0.001). More pediatric than adult patients had a PNH clone of <10% and severe cytopenia (Table). Pediatric patients had lower percent of reticulocytes compared with adults (2.1% vs. 2.6%, respectively; p=0.015). History of aplastic or hypoplastic anemia was more frequent in pediatric than adult patients (76.5% vs 54.4%, respectively; p<0.001). History of TE and any major adverse vascular event was less frequent in pediatrics (2.1% vs 8.7%; p=0.025, and 4.3% vs. 14.4%; p=0.005). The rate of TE between disease start and enrollment was lower in pediatric patients, but not statistically significant: 1.4 per 100 person-years (95%CI 0.2-5.2) compared to adult patients (2.3 per 100 person-years (95%CI 2.0-2.6). More pediatric patients than adults had abdominal pain at enrollment.

Conclusions: The International PNH Registry provides the largest available pediatric cohort of patients with a PNH clone to characterize this understudied population and demonstrate an important disease burden. Pediatric patients were more likely to have smaller PNH clones and a higher component of aplastic/hypoplastic anemia. Pediatric patients had fewer vascular events. These findings may reflect the natural evolution of the disease and can be useful in the clinical management of PNH.

Table. Clinical Characteristics at Enrollment of Pediatric and Adult Patients with PNH

Pediatric

(n=94)

Adult

(n=2,090)

P-value

Clone size (percent GPI-deficient granulocytes), n (%)

<10%

10 to < 50%

³50%

 

47 (55.3)

16 (18.8)

22 (25.9)

 

550 (38.3)

322 (22.4)

565 (39.3)

 

0.006*

Cytopenia status, n (%)

None (neutrophils ³ 1.5 x 109/L and platelets ³100 x 109/L)

Moderate (neutrophils <1.5 x 109/L or platelets <100 x 109/L)

Severe (neutrophils <0.5 x 109/L or platelets <20x109/L)

 

22 (29.3)

28 (37.3)

25 (33.3)

 

735 (42.2)

784 (45.1)

221 (12.7)

 

<0.001*

Percent reticulocytes

Median (Q1, Q3)

2.1 (1.1, 3.5)

2.6 (1.6, 4.6)

0.015

Hemolytic status, n (%)

Hemolytic (LDH ³1.5 x ULN and/or reticulocytes ³60 x 109/L)

Not hemolytic (LDH <1.5 x ULN and reticulocytes <60 x 109/L)

 

33 (58.9)

23 (41.1)

 

1,038 (65.3)

551 (34.7)

 

NS

LDH Ratio, n (%)

<1.5 x ULN

³1.5 x ULN

 

30 (58.8)

21 (41.2)

 

684 (47.0)

770 (53.0)

 

NS

History of TE, n (%)

Yes

No

 

2 (2.1)

92 (97.9)

 

181 (8.7)

1,902 (91.3)

 

0.025

Rate of TE

Number of TE, n

Person-years (disease start to enrollment)

Rate/100 person-years (95% CI)

 

2

139.9

1.4 (0.2-5.2)

 

255

11,119.8

2.3 (2.0-2.6)

 

NS

History of MAVE, n (%)

4 (4.3)

300 (14.4)

0.005

GPI, glycosylphosphatidylinositol; LDH, lactate dehydrogenase; MAVE, major adverse vascular event; TE, thrombotic event; ULN, upper limit of normal

*P-values for clone size and cytopenia status represent overall comparison of categories.

Disclosures: Muus: Alexion Pharmaceuticals: Honoraria . Schrezenmeier: Alexion Pharmaceuticals: Membership on an entity’s Board of Directors or advisory committees , Research Funding , Speakers Bureau . Almeida: Celgene: Consultancy ; Novartis: Consultancy ; Bristol Meyer Squibb: Speakers Bureau ; Shire: Speakers Bureau . Wilson: Alexion Pharmaceuticals: Employment . Ware: Bayer Pharmaceuticals: Consultancy ; Biomedomics: Research Funding ; Eli Lilly: Other: DSMB membership ; Bristol Myers Squibb: Research Funding .

*signifies non-member of ASH