Supportive therapies are required in all MDS patients and may be the only long-term treatment required for those with lower risk disease, or for older or unfit patients and those who have not responded to other treatments (Fenaux et al. 2021).

Supportive therapy may include the following:

• Conduct regular blood tests and review appointments with the patient’s general practitioner and specialist to monitor progress and symptoms.
• Manage anaemia, including red blood cell transfusions – frequency will be determined by symptoms and comorbidities.
• Manage bleeding, which may include platelet transfusions or tranexamic acid when
• Manage infections – prompt antibiotics for infection and consideration of short-term use of growth factors (e.g. GCSF). Infectious disease consultation may be required if infections recur. Anti-fungal prophylaxis may be considered in patients with persistent severe neutropenia depending on local guidelines and practice.
• Consider iron chelation therapy for transfusional iron overload. In general, this is considered for patients with significant transfusion burden and evidence for iron overload. Both oral and

Parenteral chelation therapy options are available and could be tailored to the patient depending on clinical need.

• Manage gastrointestinal symptoms such as nausea, vomiting, loss of appetite, dysgeusia, diarrhoea or constipation as a result of treatment. This requires optimal symptom control with medicine, nutritional advice, analgesia and mouth care (referral to a dietitian may be required if dietary intake is affected).

Timeframe for starting treatment

The timeframe for starting treatment should be guided by clinical presentation and urgency and disease progression over time.

Training and experience required of the physician

Documented evidence of the physician’s training and experience, including their specific (sub-specialty) experience with MDS and procedures to be undertaken, should be available.

Health service characteristics

To provide safe and quality care for patients, health services should have these features:

• medical staff availability
• diagnostic imaging

In patients with lower risk MDS, anaemia is the most common cytopenia. Erythropoiesis-stimulating agents may be used as first-line therapy.

Available treatment options include (Stojkov et al. 2020; Volpe & Komoroji 2021):

• lenalidomide – specifically approved for patients with transfusion-dependent lower risk MDS with del(5q) abnormality in their karyotype analysis
• hypomethylating agents (HMAs) including azacitidine in patients who progress to higher risk MDS
• immunosuppressive therapy to provide some haematological response among selected subsets of patients.

Timeframe for starting treatment

The timeframe for starting treatment should be guided by clinical presentation and urgency.

Training and experience required of the physician

Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in haematology.

Health service characteristics

To provide safe and quality care for patients having treatments, health services should have these features:

• critical care support
• 24-hour medical staff availability
• 24-hour high dependence or intensive care unit
• diagnostic imaging
• pathology diagnostics
• ready access to blood banking and transfusion

Survival for these patients is generally poor, so if appropriate for the disease, directed therapy treatment should be initiated promptly.

Standard therapies include (Bewersdorf et al. 2020; Sekeres & Cutler 2014) the following:

• hypomethylating agents (HMAs azacitidine and decitabine). Azacitidine has shown a survival benefit in patients with higher risk MDS and is the mainstay of therapy, with clinical benefit and haematological responses seen even in those who don’t achieve a complete remission. Treatment is usually continued for at least 6 months and continued based on response, though dose reductions or delays may be required in some patients.
• AML induction This can be considered in those with a high blast count and who are eligible for intensive therapy.
• Haematopoietic stem cell transplantation close to the time of diagnosis, depending on the patient’s goals of Consider proceeding to transplantation soon after an optimal donor is located.
• In the interim period before transplantation, HMA therapy, AML induction chemotherapy or enrolment in a clinical trial should be considered to prevent disease progression, although the optimal pre-transplantation therapy is unknown.

Timeframe for starting treatment

For symptomatic patients with higher risk disease, a decision about disease-specific therapy should be made and treatment begun within the first six weeks of initial specialist consultation. At times, depending on disease stability and symptoms, ongoing close monitoring could be considered depending on the patient’s circumstances.

Training and experience required of the physician

Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in haematology.

To oversee higher risk MDS patient care, the physician should have worked or be working in a team with experience in managing MDS and AML, and specifically the use of HMAs or intensive chemotherapy.

Documented evidence of the physician training and experience, including their specific (sub-specialty) experience with MDS and procedures to be undertaken, should be available.

Cancer nurses should have accredited training in these areas:

• anti-cancer treatment administration
• specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
• the handling and disposal of cytotoxic waste (ACSQHC 2020).

Systemic therapy should be prepared by a pharmacist whose background includes adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.

In a setting where no haematologist or medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.

Health service characteristics

To provide safe and quality care for patients having systemic therapy for higher risk MDS, health services should have these features:

• critical care support
• 24-hour medical staff availability
• 24-hour high dependence or intensive care unit
• diagnostic imaging
• pathology diagnostics
• ready access to blood banking and transfusion

Allogeneic stem cell transplantation is the only potentially curative treatment of MDS (Bewersdorf et al. 2020; Skeres & Cutler 2014). In this procedure, the patient receives blood-forming cells (stem cells) from a healthy donor (related or unrelated) to replace their own stem cells following chemotherapy and, in some cases, radiation.

Patients may have additional supportive care requirements to address the immunosuppressive effects and long-term side effects of stem cell transplantation. Issues may include infertility, GVHD, increased risk of infection, iron overload or anaemia, bleeding, mouth ulcers and fatigue.

Timeframe for starting treatment

A referral to a bone marrow transplant specialist should occur once transplantation is considered a potential treatment option for a patient with higher risk MDS and occasionally lower risk MDS.

Early referral to a transplant specialist is recommended for patients under 70 years of age and with higher risk MDS. Age-specific frailty scores and performance status should be considered for such a referral rather than an absolute age cut-off.

Training and experience required of the physician

Documented evidence of the physician’s training and experience (e.g. Fellow of the Royal Australian College of Physicians or equivalent) with adequate training and experience that enables institutional credentialing and agreed scope of practice in bone marrow transplantation.

Documented evidence of the physician’s training and experience, including their specific (sub- specialty) experience with MDS and procedures to be undertaken, should be available.

Health service characteristics

To provide safe and quality care for patients having haematopoietic stem cell transplant, health services should have these features:

• critical care support
• 24-hour medical staff availability including access to consultative medical subspeciality services
• 24-hour operating room access, high dependency unit and intensive care unit
• bone marrow transplantation unit with ancillary medical and allied health support
• diagnostic imaging
• pathology diagnostics
• ready access to blood banking and transfusion

Combinations of hypomethylating agents (HMAs, especially with immune checkpoint inhibitors, have shown promising signals in both the frontline and HMA-refractory setting.

Several other novel agents including orally available and longer acting HMAs, the BCL-2 inhibitor venetoclax, oral agents targeting driver mutations (IDH1 and IDH2, FLT3), immunotherapies and new options for intensive chemotherapy are being studied in clinical trials (Bewersdorf et al. 2020). Examples of non-chemotherapy approaches include therapy targeting marrow microenvironment and immune checkpoints such as TIM-3 and antiCD47 monoclonal antibody-magrolimab.

Examples of new treatments for adults with MDS, approved by the America’s Food and Drug Administration, include luspatercept (Reblozyl) for lower risk MDS and the oral combination of decitabine and cedazuridine (Inqovi) for higher risk MDS (Harris 2020).

Clinical trials for MDS may be available, especially in those with higher risk disease, and they may also be eligible for AML trials. Refer to section 4.4 for clinical trial resources.

The key principle for precision medicine is prompt and clinically oriented communication and coordination with an accredited laboratory and pathologist. Tissue analysis is integral for access to emerging therapies and, as such, tissue specimens should be treated carefully to enable additional histopathological or molecular diagnostic tests in certain scenarios.