From the Guidelines
Congenital Bone Marrow Failure is a group of heterogeneous diseases associated with inadequate blood cell production, constitutional malformations, and predisposition to cancer 1.
Causes
The causes of Congenital Bone Marrow Failure include:
- Genetic mutations that affect the production of blood cells, such as those found in Fanconi’s anaemia and dyskeratosis congenita 1
- Constitutional malformations that increase the risk of cancer and other health problems
Symptoms
The symptoms of Congenital Bone Marrow Failure include:
- Cytopenias, or low blood cell counts, which can lead to anemia, infections, and bleeding disorders
- Increased risk of malignancies, particularly gynaecological and head and neck squamous cell carcinomas 1
- Constitutional malformations, such as physical abnormalities and developmental delays It is essential to note that cancer prevention strategies are crucial for patients with Congenital Bone Marrow Failure syndrome due to their increased risk of cancer 1.
From the Research
Causes of Congenital Bone Marrow Failure
- Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of genetic disorders characterized by bone marrow failure, congenital anomalies, and an increased risk of malignant disease 2
- The representative diseases with trilineage involvement are Fanconi anemia and dyskeratosis congenita, while the disease with the single lineage cytopenia is Diamond-Blackfan anemia 2
- Recent advances in understanding these diseases have come from the identification of genetic lesions responsible for the disease and their pathways 2
- Classical IBMFSs primarily include Fanconi anemia with impaired DNA damage repair, dyskeratosis congenita with telomere maintenance dysfunction, and Diamond-Blackfan anemia with aberrant ribosomal protein biosynthesis 3
Symptoms of Congenital Bone Marrow Failure
- IBMFS feature complex molecular pathophysiology resulting in ineffective hematopoiesis and increased risk of progression to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) 4
- Patients with IBMFS may present with bone marrow failure, congenital anomalies, and an increased risk of malignant disease 2
- The phenotypical heterogeneity associated with extramedullary abnormalities has to be carefully evaluated before hematopoietic stem cell transplantation (HSCT) because transplantation may only correct impaired hematopoiesis 4
- HSCT may be associated with the risk of treatment-related mortality and with significant early and late morbidity 4
Treatment and Outcomes
- Allogenic hematopoietic stem cell transplantation (HSCT) is the only well-established cure for the hematological manifestations of these diseases 4
- A 'disease-specific' HSCT using an optimized conditioning regimen based on the characteristics of the disease is essential for achieving long-term survival 4
- The outcomes of pediatric patients diagnosed with BMF treated in a tertiary care center include a 5-year overall survival (OS) of 83% for patients treated with HSCT 5
- The most frequent cause of death was of infectious origin, which has also been previously reported 5