Page 44 - Haematologica March 2020

A.D. Shapiro et al.
dedicated website (www.plgdeficiency.com), presentations at international meetings, and direct contact with interested colleagues will be pursued. Study coordinators at IRCCS/UNIMI will contact their established treatment cen- ter network throughout the world. In addition to hematol- ogists, specialists including gynecologists and ophthalmolo- gists will also be contacted; these healthcare professionals may be the first to observe a patient with PLGD. A multi- disciplinary approach including such specialists is essential to improve overall awareness and understanding of the dis- order; it may also prevent the loss of patients to follow-up by a hematologist as some patients may continue treatment outside of a specialist hematology center. As PLGD may affect different systems throughout life, the investigators are enrolling subjects across a wide range of ages, countries, phenotypes and genotypes. People with PLGD are motivat- ed to participate in studies to advance PLGD understanding as few study opportunities exist.
A
To date, 26 centers from 12 countries have agreed to par- ticipate in HISTORY; 51 subjects (24 probands and 27 first-degree family members) are currently enrolled in the study. Demographic data for these 51 subjects are shown in Table 4. Initial results have identified asymptomatic siblings with PLGD; these subjects are being monitored to understand the factors that trigger initial symptom development.
Therapeutic interventions
Regular monitoring and individualization of therapy is required for people with PLGD as there is currently no compelling evidence that a patient’s clinical course can be predicted from their plasminogen activity level or genetic defect.12 Similarly, if a patient presents with ligneous con- junctivitis, the likelihood of developing multisystem dis- ease cannot be predicted; it is unknown what routine scans should be performed, what surveillance methods
B
Figure 1. Overall study timeline and scheduled study visits. (A) The 4-year study plan includes a 1-year enrollment period and a maximum 3-year on-study period for each subject enrolled. Retrospective clinical data for 1 year prior to study enrollment will also be collected. (B) The initial baseline visit will include informed consent, demographics, screening, laboratory investigations, genetic testing, medical examination and history, and a 1-year retrospective collection of relevant clinical data. Subsequent study visits will occur every 6 months and will include a medical history review; the closeout visit will occur at the 3-year time point. See also Table 3.
Table 2. Inclusion and exclusion criteria for enrollment in HISTORY Inclusion criteria
Males or females with plasminogen deficiency diagnosed locally
with plasminogen activity levels <50% OR first-degree family members of a person diagnosed with plasminogen deficiency (to include parents, siblings, half-siblings)
All ages eligible
Available clinical history and treatment for at least 1 year prior to entry except for infants <1 year of age
Willingness to provide samples for analysis including DNA, plasma etc.
Exclusion criteria
Any psychiatric disorder, other mental disorder, or any other medical disorder that impairs the subject’s ability to give informed consent or to comply with the requirements of the study protocol (unless a caregiver or authorized representative is willing to provide consent/assent)
Previous organ transplant recipient Refusal to provide informed consent
Special patient populations, including prisoners or those who are deemed
medically or cognitively unsuitable for research by their treating physician
Inability to obtain a blood sample due to poor or limited venous access
Willingness to participate in prospective follow-up for up to 3 years
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haematologica | 2020; 105(3)