title: Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome.
abstract: BACKGROUND
  Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications.
  
  
  METHODS
  One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant.
  
  
  RESULTS
  Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.
authors.affiliation: AP-HP Registre Français des Neutropénies Congénitales, Hôpital Trousseau, Service d’Hémato-oncologie Pédiatrique, APHP, Paris, France. jean.donadieu@trs.aphp.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Odile
authors.initials: O
authors.lastname: Fenneteau
authors.forename: Blandine
authors.initials: B
authors.lastname: Beaupain
authors.forename: Sandrine
authors.initials: S
authors.lastname: Beaufils
authors.forename: Florence
authors.initials: F
authors.lastname: Bellanger
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.forename: Anne
authors.initials: A
authors.lastname: Lambilliotte
authors.forename: Nathalie
authors.initials: N
authors.lastname: Aladjidi
authors.forename: Yves
authors.initials: Y
authors.lastname: Bertrand
authors.forename: Valérie
authors.initials: V
authors.lastname: Mialou
authors.forename: Christine
authors.initials: C
authors.lastname: Perot
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.forename: Fanny
authors.initials: F
authors.lastname: Fouyssac
authors.forename: Catherine
authors.initials: C
authors.lastname: Paillard
authors.forename: Virginie
authors.initials: V
authors.lastname: Gandemer
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Jacques
authors.initials: J
authors.lastname: Schmitz
authors.forename: Alain
authors.initials: A
authors.lastname: Morali
authors.forename: Thierry
authors.initials: T
authors.lastname: Leblanc
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
mesh_terms: D001855:Bone Marrow Diseases / Q000150:complications* / Q000401:mortality; D010188:Exocrine Pancreatic Insufficiency / Q000150:complications* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006402:Hematologic Diseases / Q000145:classification* / Q000209:etiology* / Q000401:mortality; D006801:Humans; D007223:Infant; D008068:Lipomatosis / Q000150:complications* / Q000401:mortality; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D000081003:Shwachman-Diamond Syndrome; D015996:Survival Rate