Myelodysplastic syndromes (MDS), now classified as neoplasms by the World Health Organization, are a group of blood disorders that affect the bone marrow.¹ These disorders occur when the bone marrow produces abnormal blood cells that fail to mature into healthy blood cells. Myelodysplastic syndromes are characterised by refractory cytopenias (anaemia, thrombocytopaenia and neutropenia) and progression to acute myeloid leukaemia (AML) in a third of individuals.^2,3,4

Primary care providers may be the first point of contact for patients presenting with symptoms of MDS. They should therefore be familiar with MDS and consider further investigation of patients with cytopenia. Early identification and appropriate management or referral can improve patient outcomes and reduce the risk of progression to AML.

The incidence of MDS is about four to five cases per 100 000 people per year (more common in males), increasing to 40–50 per 100 000 in people older than 70 years.⁵ The cause is unknown in most cases but about 15% of cases occur after chemotherapy or radiotherapy for cancer.⁶ Other suspected factors include tobacco smoking and occupational exposure to solvents or agricultural chemicals.² Autoimmune diseases (such as hypothyroidism, thyroiditis, ulcerative colitis, rheumatoid arthritis and systemic lupus erythematosus [SLE]) have also been associated with the development of MDS. The pathophysiology of MDS is thought to involve cytogenetic changes and/or gene mutations with widespread gene hypermethylation in advanced disease.²

Patients with MDS can be asymptomatic in the early stages with only an incidental finding of cytopenia in a routine blood test. The most common cytopenia associated with MDS is anaemia, found in 80% – 85% of patients. Anaemia associated with MDS is usually macrocytic or normocytic.⁷ Thrombocytopenia is found in 35% – 45% of patients, and neutropenia in about 40%. The symptoms and signs associated with MDS are related to the cytopenia and vary in severity. They can include pallor, fatigue, dyspnoea, palpitations, fever, recurrent infections, bruising and abnormal bleeding.⁷ In more extreme cases of thrombocytopenia, gastrointestinal bleeding or intracranial haemorrhage may occur.

It can be difficult to suspect MDS in patients presenting with anaemia alone as there is a high prevalence of anaemia in South Africa because of nutritional deficiencies and other diseases, notably human immunodeficiency virus (HIV) and TB.^8,9 A systematic approach should be adopted to identify the specific cause of the cytopenia and refer those individuals with high risk of MDS. Furthermore, MDS should be always considered in the differential diagnosis of any older adult with unexplained or persistent cytopenia (lasting six months or longer). Figure 1 outlines a practical approach for primary care providers to diagnose MDS.

History taking in a patient with cytopenia (with or without symptoms and signs) should include an inquiry into occupation, medical conditions, medications and alcohol use. The presence of pallor, purpura, petechiae, hepatomegaly, splenomegaly or lymphadenopathy on physical examination should prompt further investigations. These could include the following:

The prognosis of patients with MDS varies greatly and is predicted using validated scoring systems such as the International Prognostic Scoring System (IPSS).¹¹ Factors such as the percentage of blasts, karyotype and number of cytopenias influence the prognosis.¹² Advancements in molecular methods, such as next-generation sequencing (NGS), have enabled the integration of molecular data into risk stratification systems, that is IPSS-M, thereby enhancing the prognostic capabilities of traditional scoring systems.⁷ Those with low-risk MDS have a median survival of three to ten years, while individuals with high-risk disease have a median survival of less than three years.

First-line treatment for those with higher-risk MDS is with hypomethylating agents (such as azacitidine, decitabine or decitabine/cedazuridine) and, if possible, stem-cell transplantation. Haematopoietic stem cell (HSC) transplant is currently the only potentially curative treatment for MDS. However, less than 10% of affected individuals receive this treatment because of limiting factors which include patient age, comorbidities and donor availability. Recent advancements in haematological oncology aim to optimise transplant outcomes by improving patient selection, employing targeted therapies to achieve deeper molecular responses, developing conditioning regimens with reduced toxicity, enhancing molecular tools for early relapse detection and incorporating maintenance strategies post-transplant.^2,13,15

The diagnosis of AML is made when there are at least 20% myeloid blasts (immature cells) in the blood or bone marrow and should be managed by a specialist clinical haematologist.

The goals of treatment for AML are to eradicate the myeloid blasts to the lowest level possible (remission), usually <5% blasts in the bone marrow. The only possible cure is stem cell transplantation.

The long-term survival rate following a stem cell transplant ranges from 40% to 50%. However, outcomes depend on factors such as the patient’s age, prognostic scores and donor characteristics. The procedure involves administering high-dose chemotherapy, and in some cases radiation, followed by an infusion of stem cells.

Haematopoietic stem cells that are progenitor cells can be derived from three main sources:

However, peripheral blood stem cells (PBSC) are the most common source of stem cells and are used in over 80% of adult haematopoietic stem cell transplantation (HSCT) worldwide.

The transplant day, referred to as ‘Day 0’, involves infusing the harvested stem cells through a central venous line. The procedure may take 1–2 h to complete.

Engraftment is the process by which transplanted HSCs travel to and settle in the bone marrow and begin producing new blood cells (red blood cells, white blood cells and platelets).¹⁷ Several factors contribute to successful engraftment including the physical condition of the patient, severity of disease, age of patient, type of donor and the HSCT conditioning regimen.¹⁵ It is a key milestone in the recovery process after a stem cell transplant. Engraftment usually occurs within 2–4 weeks after a stem cell transplant. White blood cells are usually the first to engraft, followed by red blood cells and platelets.

While HSCT can be lifesaving, it is associated with risks and potential side effects, both short-term and long-term.¹⁷ A summary of short-term and long-term complications is provided in Table 1.

In the first three months patients should be monitored for complications and strict infection prevention strategies should be followed. Any side-effects can be managed symptomatically.

After three months, patients will need to be reviewed regularly for long-term complications, such as damage to organs like the liver, kidney, lungs and heart. Other potential issues include cataracts, bone and muscle weakness and problems with hormone production, such as an underactive thyroid or type 1 diabetes, and new malignancies. An essential aspect of care is to offer mental health support and address physical and emotional challenges.

Primary care providers need to work with specialists to ensure smooth transition of care before, during and after transplant.

Primary care providers should consider MDS, especially in older individuals who present with cytopaenias. Modalities of treatment include disease-modifying therapies, chemotherapy and radiotherapy. Stem cell transplantation is the only possible cure for higher-risk MDS and AML. However, there is a need for increased awareness and drive to improve the donor registry.