Periodic Evaluation Of The Clone Size Is Mandatory In PNH: Study Of The Spanish Cohort Of The International PNH Registry
Authors: Villegas Ana , Gaya Ana , Ojeda Emilio , Gonzalez Ataulfo , Urbano Alvaro , Roncero Isabel Gomez , Cuevas Maria Victoria , Cordoba Raul , Jarque Isidro , NuÃ±ez Ramiro , Arrizabalaga Beatriz 
Published: October 2019

Abstract

Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, life threatening hematopoietic stem cell disorder with chronic hemolytic anemia, peripheral blood cytopenias and thrombosis

Aims
To observe the PNH clone and LDH evolution of the Spanish patients enrolled in the International PNH Registry, the thrombotic events and the role of eculizumab

Methods
We analyzed the 117 patients enrolled in the Registry until Dec. 31st 2012, classified in 3 groups: Classic/ hemolytic (group I, n 59), PNH with another bone marrow disorder (group II, n 42) and Subclinical (group III, n 14). The variables analyzed were PNH clone size, LDH levels, and incidence of thrombosis. Medians and percentages should be taken with caution due to the relatively small sample size. In addition to data collected in the Registry, additional patient information was obtained from local physicians.

Results
The median (range) age at presentation was 36.6 yrs. (16-83); 48 patients (41.0%) were women. Median (range) time from disease start to enrollment was 11.3 years in group I (0.1-41.2), 3.5 in II (0.1-33.8) and 3.4 (0.3-20.8) in III.
A total of 49 patients (39 in group I) were started on eculizumab, 38 prior to enrollment (31 in group I) and 11 on or after enrollment; 3 were treated prior to enrollment but discontinued for different reasons (pregnancy, ending trial, access problems).
Clone evolution (Table 1). In group I the median clone size remained stable during the follow-up period in the Registry; however, 4 patients in group II evolved to group I, with granulocyte clones > 50% and LDH levels >2000 U/L, while 3 initially in group I evolved to group II at 6, 12 and 18 months respectively. At enrollment 64 patients had a clone ≥30% and 31<30%; 7 patients in group II had a clone ≥30% despite hypoplasia, and they were treated with eculizumab. In groups I and II median clone size increased from Diagnosis to Enrollment in line with the physiopathology of the disease.
LDH evolution (Table 2). Median LDH levels at diagnosis were higher in group I. In this group the decrease in LDH level between Diagnosis and Enrollment could be attributed to the start of treatment in 31 patients before the enrollment visit, but that hypothesis will need confirmation in future analysis.
Thrombotic episodes (Table 3). Twenty six patients (22.6%) presented 52 TEs along the study period, 41 in group I and 11 in group II. Of the 26, fourteen presented 1 TE, six 2, one 3, four 2 and one 5. Twenty five patients presented 51 TEs since the moment of diagnosis while they were not being treated with eculizumab. Only one patient in the treated group presented a TE (CVA), of which he recovered well; after 30 months of the episode continues with the treatment and scores 90 in the Karnofsky index. Fifty eight percent of the patients presenting TEs were male, showing they may be more prone to TE than women.

Conclusions
These data show the dynamic features of the disease in some patients, which justifies the necessity of regularly monitoring the clone size
LDH levels are higher in patients with classical PNH at diagnostic; the effect of the treatment in the whole cohort will require future analysis
Thrombosis is highly prevalent in PNH; 22.6% of the patients in this sample had at least 1 episode along their time in the study.

Disclosures:
No relevant conflicts of interest to declare.