Hematological Anomalies in Children With Rasopathy

Обзор

During childhood, patients with RASopathies (Noonan syndrome and related diseases) can harbor various hematological anomalies ranging from isolated monocytosis, myelemia, thrombocytopenia or splenomegaly to myeloproliferative disorders. These anomalies may spontaneously disappear or persist, sometimes leading to juvenile myelomonocytic leukemia. Guidelines for initial screening and subsequent hematological follow-up have recently been published in France: peripheral blood analysis should be performed in all newly diagnosed patients and followed by biannual peripheral blood analysis in infants until the age of 2 years. In order to describe the characteristics of these abnormalities in terms of their incidence, age of occurrence, evolution and relation to genotype, we are conducting a longitudinal prospective study whose aim is to analyze peripheral blood cell counts and smears at diagnosis and one year later. In patients \<3 years of age recruited at certain centers, biobanking of mononuclear cells will be performed. These data could yield a new insight into hematological anomalies in patients with RASopathies and thereby help physicians to determine the appropriate rhythm for hematological follow-up according to genotype.

Первичные конечные точки

• Proportion of patients with hematological abnormalities [Срок оценки: at inclusion (within 6 months after diagnosis)]

Вторичные конечные точки (8)

• Proportion of patients with hematological abnormalities according to genetic abnormality [Срок оценки: at inclusion (within 6 months after diagnosis)]
• Proportion of patients with hematological abnormalities according to age [Срок оценки: at inclusion (within 6 months after diagnosis)]
• Proportion of patients with hematological abnormalities [Срок оценки: at 1 year after inclusion]
• Proportion of patients with hematological abnormalities according to age [Срок оценки: at 1 year after inclusion]
• Proportion of patients with hematological abnormalities according to genetic abnormalities [Срок оценки: at 1 year after inclusion]
• Evolution of proportion of patients with hematological abnormalities during childhood [Срок оценки: at 5 years post-inclusion]
• Event-free survival [Срок оценки: at one year post-inclusion]
• Event-free survival [Срок оценки: at 5 years post-inclusion]

Критерии участия

Критерии включения

• Age < 16 years
• Patient newly diagnosed with genetically confirmed rasopathy : Noonan syndrome, type 1 neurofibromatosis, Noonan syndrome with multiple lentigines, CBL syndrome, Costello syndrome, cardiofaciocutaneous syndrome or Legius syndrome i.e. with a germline mutation of one of these genes: PTPN11, SOS1, NRAS, RAF1, BRAF, SHOC2, MEK1, MEK2, CBL, NF1, SPRED1, KRAS, HRAS, NF1, SHOC2, LZTR1, SOS2, RIT1, RASA2, RRAS, PPP1CB, or a new gene of interest published during the recruitment period
• No history of hematological malignancy
• Written informed consent obtained from the parents
• Health insurance

Критерии исключения

• History of malignant hematological pathology

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 14 центров

• CHU Angers — Angers
• CHU Caen — Caen
• CHU Lille — Lille
• CHU Lyon — Lyon
• CHU Marseille - Hôpital de la Timone — Marseille
• CHU Montpellier — Montpellier
• CHU Nantes — Nantes
• Hôpital Necker APHP — Paris
• … и ещё 6 центров

Идентификаторы

NCT: NCT04286360 · K171010J

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗