History and exam

Key diagnostic factors

common

older age

MDS occurs primarily in older adults; median age at diagnosis is 70-75 years.[9][10]​

MDS can occur at any age and should be considered in younger patients with prior exposure to chemotherapy or radiotherapy, or who have a congenital disorder.

fatigue

Usually related to anaemia, which is common on diagnosis.[56]

Patients may be asymptomatic, with cytopenia an incidental finding during routine blood tests.

exercise intolerance

Symptom of anaemia, which is common on diagnosis.[56]

Patients may be asymptomatic, with cytopenia an incidental finding during routine blood tests.

pallor

Associated with anaemia, which is common on diagnosis.[56]

Patients may be asymptomatic, with cytopenia an incidental finding during routine blood tests.

bruising or bleeding

Bruising or bleeding (including petechiae and purpura) due to thrombocytopenia occurs in approximately 20% of patients.[56] This may become more prominent as disease progresses.

Patients may be asymptomatic, with cytopenia an incidental finding during routine blood tests.

uncommon

prior chemotherapy and/or radiotherapy

MDS should be considered in younger patients who have had prior exposure to chemotherapy and/or radiotherapy.[35][36][37][38][39]

congenital disorder

MDS should be considered in younger patients who have a congenital disorder, such as an inherited bone marrow failure syndrome (e.g., Fanconi anaemia, Diamond-Blackfan anaemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia [Kostmann syndrome]), Down syndrome (trisomy 21), ataxia telangiectasia, xeroderma pigmentosum, Bloom syndrome, glutathione transferase theta 1 (GSTT1) gene defect, and Li-Fraumeni syndrome.[15][16][18][26]​​[27]​​[28][29][30]

bacterial infections

Approximately 40% to 50% of MDS patients have neutropenia; only a subset has recurrent infections, usually bacterial.[3][57]

Other diagnostic factors

uncommon

presence of risk factors

Key risk factors include: age >70 years; prior chemotherapy; prior radiotherapy; prior autologous haematopoietic stem cell transplantation; and congenital disorders.

autoimmune disorders

Autoimmune disorders (e.g., vasculitis, connective tissue disease, inflammatory arthritis) are reported in approximately 25% of MDS patients.​[6][7][8]

splenomegaly

Rare in MDS. Can occur in chronic myelomonocytic leukaemia (CMML), a myeloid neoplasm with pathological and molecular features that overlap with MDS.[1]

hepatomegaly

Rare in MDS. Can occur in chronic myelomonocytic leukaemia (CMML), a myeloid neoplasm with pathological and molecular features that overlap with MDS.[1]

lymphadenopathy

Rare in MDS. Can occur in chronic myelomonocytic leukaemia (CMML), a myeloid neoplasm with pathological and molecular features that overlap with MDS.[1]

Risk factors

strong

age >70 years

MDS occurs primarily in older adults; median age at diagnosis is 70-75 years.[9][10]​

MDS can occur at any age and should be considered in younger patients with prior exposure to chemotherapy or radiotherapy, or who have a congenital disorder.

prior chemotherapy

Alkylating agents (e.g., chlorambucil, cyclophosphamide, melphalan), topoisomerase inhibitors (e.g., etoposide, teniposide), anthracyclines (e.g., doxorubicin, daunorubicin), and platinum agents (e.g., cisplatin, carboplatin) are associated with an increased risk for secondary MDS.[35][36]​​​[37]

prior radiotherapy

Radiotherapy is associated with an increased risk for secondary MDS.[37] Radiotherapy combined with chemotherapy increases the risk compared with radiotherapy alone.[38][39]

prior autologous haematopoietic stem cell transplantation

Likely to be related to DNA damage from chemotherapy agents (e.g., conditioning regimens) prior to autologous haematopoietic stem cell transplantation.[40]

congenital disorders

MDS in children and younger adults is often associated with congenital disorders.[18]

Risk of MDS is increased in those with inherited bone marrow failure syndromes (e.g., Fanconi anaemia, Diamond-Blackfan anaemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia [Kostmann syndrome]), Down syndrome (trisomy 21), ataxia telangiectasia, xeroderma pigmentosum, Bloom syndrome, glutathione transferase theta 1 (GSTT1) gene defect, and Li-Fraumeni syndrome.[15][16][18][26][27][28][29][30]​

weak

tobacco

A known mutagen.[32]

benzene

Observational data suggest an increased risk of developing MDS following occupational exposure to benzene.[44][45] Possible mechanisms include inducing apoptosis, altering the bone marrow micro-environment, and inducing immunological dysregulation.[46]

aplastic anaemia

Can transform into MDS.[18][31]​​

paroxysmal nocturnal haemoglobinuria (PNH)

MDS clone can arise.[18][31]​​

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