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.

Design and 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.

Figure 1.

Kaplan-Meier plot showing the risk of severe cytopenia. The events analyzed are: (A) any severe cytopenia, (B) non-malignant severe cytopenia and (C) malignant severe cytopenia (MDS/leukemia). The time is expressed in years since birth.

Figure 2.

Kaplan-Meier plot showing the risk of severe cytopenia according to the severity score. The time is expressed in years since birth. The severity score is divided into three groups: high risk group if patients are diagnosed before the age of 3 months old AND if the first complete blood count exhibited either neutropenia <0.5×10⁹/L or anemia <9 g/L or thrombocytopenia <100×10⁹/L; intermediate risk group if patients are diagnosed before the age of 3 months old OR if the first complete blood count exhibited either a neutropenia <0.5 ×10⁹/L or anemia <9 g/L or thrombocytopenia <100×10⁹/L; low risk if the patients are diagnosed after 3 months old and have no severe or mild hematologic abnormalities in their first blood count.