[WHIM syndrome: presumptive diagnosis based on myelokathexis on bone marrow smear]. / Diagnostic de syndrome WHIM évoqué devant l'observation de myélokathexis.

The WHIM syndrome is a rare congenital immunodeficiency disorder characterized by human papillomavirus (HPV)-induced warts, hypogammaglobulinemia, bacterial infections and myelokathexis. Myelokathexis refers to abnormal retention of mature neutrophils in the bone marrow leading to severe neutropenia. We report the case of a 20 year old man presenting with chronic and severe neutropenia since early childhood without established diagnosis. He was addressed for chronic parodontal disease treatment. Examination of bone marrow smear showed morphological abnormalities of mature neutrophils strongly suggestive of myelokathexis. Diagnosis of WHIM syndrome was confirmed by molecular analysis: a nonsense mutation was identified in the gene encoding CXCR4, the CXCL12 (or SDF-1) chemokine receptor which notably controls cell adhesion to the marrow stroma and thereby regulates mature leukocytes release from the bone marrow. Treatment of the disease usually consists in prophylactic anti-infective measures including intravenous immunoglobulins administration, oral antibiotic prophylaxis and more recently HPV vaccination. Long term G-CSF therapy did not show any significant efficiency in preventing recurrent infections. The use of specific CXCR4 antagonist is being currently evaluated.

Shwachman-Diamond syndrome with late-onset neutropenia and fatal acute myeloid leukaemia without maturation: a case report.

We report on a male patient affected by Shwachman Diamond syndrome (SDS) who presented an unusual delayed neutropenia and then developed a poorly differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in adulthood. Conventional cytogenetics revealed complex karyotypic changes (monosomies 20, 21, 22, additional 15p). The patient was treated with conventional chemotherapy but never reached complete remission of leukaemia and died 18 months after diagnosis. SDS is an inherited bone marrow failure syndrome with a high propensity to leukaemic transformation. Since neutropenia may be intermittent or with delayed onset, and leukaemic transformation may not occur until adulthood, full blood count should be regularly monitored in such patients.