Proposal for the clinical detection and management of patients and their family members with familial myelodysplastic syndrome/acute leukemia predisposition syndromes

Abstract

As with most genetic cancer predisposition syndromes, inherited susceptibility to myelodysplastic syndrome (MDS) and acute leukemia (AL) is likely to be more common than previously appreciated. As next-generation sequencing technologies become integrated into clinical practice, we anticipate that the number of cases of familial MDS/AL identified will increase. Although the existence of syndromes predisposing to MDS/AL has been known for some time, clinical guidelines for the screening and management of suspected or confirmed cases do not exist. Based on our collective experience caring for families with these syndromes, we propose recommendations for genetic counseling, testing, and clinical management. We welcome discussion about these proposals and hope that they will catalyze an ongoing dialog leading to optimal medical and psychosocial care for these patients.

Myeloid neoplasms with germ line RUNX1 mutation

“…The latency until the transformation is relatively long. It has been reported that an average age at diagnosis is 33 years (up to 76 years) [23]. This trend remains unchanged in recent reports (Fig.…”

“…Currently, the guidelines of clinical management for patients and their families with familial MDS/AL predisposition syndromes are proposed [23]. At diagnosis of FPD/ AML, complete blood count (CBC), bone marrow biopsy and aspiration with cytogenetic analysis, and HLA typing of both the patients and their siblings are recommended.…”

“…At diagnosis of FPD/ AML, complete blood count (CBC), bone marrow biopsy and aspiration with cytogenetic analysis, and HLA typing of both the patients and their siblings are recommended. During follow-up, annual testing of CBC and clinical examination (every 6 months), bone marrow biopsy (when any worrying changes in CBC are observed), and consultation with hematology prior to any invasive procedures are recommended [23]. When a patient is identified as an affected individual of FPD/AML and needs to undergo allogeneic stem cell transplantation, a sibling donor, who also has RUNX1 mutations, should not be chosen.…”

“…Indeed, it has been reported that the use of donors who carry the same germ line mutations results in poor outcome [20,57]. In such a case, the use of HLA-matched unrelated donors should be considered [23].…”

“…Since peripheral blood samples from patients with hematological malignancies usually contain disease clones, the mutations identified using those samples may reflect acquired mutations rather than germ line mutations even if RUNX1 mutations are identified [23]. Thus, in this setting, alternative tissue samples, such as skin biopsy for fibroblasts, are recommended for the extraction of germ line DNA [23].…”