Bone Marrow Failure

The inherited bone marrow failure syndromes are a heterogeneous group of disorders characterized by bone marrow failure usually in association with one or more physical abnormalities. It is often present in childhood but may not present till adulthood in some patients.

Most of the disorders are Autosomal Recessive (needs defective gene from both parents) but few are Autosomal Dominant (needs defective gene from any one parent) or X-Linked (only the male child will develop the disease).

Signs and Symptoms

The symptoms are usually in the form of unilineage (only anemia or Neutropenia or thrombocytopenia) or multilineage cytopenias and infections. Many patients have physical abnormalities like short stature, darkening of skin, bone abnormalities, heart defects.

• Bleeding and Bruising
• Blood in gums, nose or the skin, tending to last longer than normal
• Blood in urine or stools
• Tooth loss or tooth decay
• Feeling tired most of the time
• Shortness of breath
• Recurring cold

FANCONI ANEMIA (FA): Children with FA have characteristic physical abnormalities. FA is characterised by the defect in DNA repair leading to extensive chromosomal breakage. Affected individuals have a very high predisposition to develop Leukemia and Myelodysplastic Syndrome.

DYSKERATOSIS CONGENITA (DKC): DKC is characterised by the triad of abnormal nails, reticular skin pigmentation and oral leukoplakia. These patients have very short telomeres and have a high risk of developing lung fibrosis and liver disease.

SHWACHMAN-DIAMOND SYNDROME (SDS): It includes bone marrow failure with exocrine pancreatic insufficiency, short stature, metaphyseal dysostosis, and a predisposition to leukemia.

SEVERE CONGENITAL NEUTROPENIA (SCN) INCLUDING KOSTMANN SYNDROME: SCN is characterized by profound peripheral neutropenia. Patients usually present with severe bacterial infections.

CONGENITAL AMEGAKARYOCYTIC THROMBOCYTOPENIA (CAMT): CAMT usually presents in infancy and is characterized by isolated thrombocytopenia and a reduction or absence of megakaryocytes in the bone marrow.

DIAMOND-BLACKFAN ANEMIA (DBA): DBA usually presents in early infancy with features of anemia. The hallmark is a profound reduction in erythroid precursors in the bone marrow.

Complete Blood Count: The characteristic findings are unilineage or multilineage cytopenia which varies with the type of disease.

Bone Marrow Study: Mainly marrow biopsy is done to confirm the hypocellularity of the marrow.

Flow Cytometry: Often performed to detect early changes of leukemia and Myelodysplastic syndrome.

Cytogenetics: Testing for abnormalities in the chromosomes. Certain genes are mutated which leads to complete absence of marrow cells.

Antenatal Screening: For mothers who have already had a child with IBMFS, prenatal testing can be done through Chorionic Villus Sampling or Amniocentesis.

Definitive cure is generally only achieved by ALLOGENEIC BMT; some disease may respond with steroids, but the disease reappears once they are withdrawn.

When is BMT needed? Best results are obtained when BMT is carried out at the earliest, before the onset of leukemia, Myelodysplastic syndrome or too many blood transfusions.

Conditioning: Reduced Intensity Conditioning with low doses of chemotherapy or radiation is the preferred option. Otherwise these patients develop severe organ damage during the BMT procedure.

Donor: Although we prefer a matched family donor, a Half Matched (Haploidentical) family donor or a Matched Unrelated donor provide excellent survival. As BMT is required as an emergency procedure in this condition, Haploidentical Family Donor is often the quickest way of finding a donor.