Myelodysplastic Syndrome (MDS)
Treatment Options
Updated: October 2010
Treatment recommendations for MDS are largely based upon general health and IPSS risk category although all patients require supportive care. Supportive care consists of blood product transfusions and antibiotic/antiviral/antifungal therapy as required. In general, all patients with “intermediate-2” (INT-2) or high-risk MDS according to the IPSS scoring system will be evaluated for stem cell transplantation or Azacitidine therapy. Patients with “low” or “intermediate-1” (INT-1) MDS will only be considered for non-transplantation treatments such as bone marrow “growth factors”, immunosuppressive therapy or immunomodulatory agents (IMiDs). At certain times, an MDS patient may be eligible for participation in a clinical trial, usually designed to evaluate a potential (but unproven) drug or combination of drugs for treating MDS. This general approach is outlined in the Treatment Algorithm.
Transfusion support
Red cell transfusions can provide symptomatic relief (of fatigue and dyspnea) for MDS patients but the transfusion threshold varies from patient to patient, depending upon age, activity level and other medical problems (especially heart and lung disease). In general, red cells should be considered for a hemoglobin <80 g/L but in the presence of heart disease, transfusions may be needed if the hemoglobin is <100 g/L. Platelet transfusions are often given when the platelet count is <10 x 109/L and may be required more than once weekly. However, patients with clinical bleeding issues may have to have a higher transfusion threshold (i.e., <20-30 x 109/L) while those without bleeding may not need (or wish) to have preemptive platelet transfusions.
Allogeneic stem cell transplantation
Stem cell transplantation (SCT) is the only proven curative treatment for MDS but is generally reserved for INT-2 and high-risk patients because of the significant risk involved. Furthermore, patients must have a suitable related or unrelated donor and be free of other medical illnesses to safely undergo this procedure. Unfortunately about 1/3 of MDS patients die of complications of SCT during the first year and another 1/3 of patients experience a relapse of their MDS. Bearing all of this in mind, 30-35% of patients that have undergone allogeneic SCT have been long-term survivors.3
Azacitidine
Azacitidine is a low-dose chemotherapy agent that is given in INT-2 and high-risk MDS by subcutaneous injection for 7 straight days every 4 weeks (See Protocols/PPOs). It is a well-tolerated drug that, on average, has been shown in a randomized study, to improve quality of life and prolong survival by 9-10 months when compared to supportive care alone (see Outcomes).4,5 It is not considered to be a curative drug. Azacitidine may cause nausea, constipation or diarrhea, inflammation at the injection site and, initially, worsening of blood counts. It is helpful in about 50% of patients with MDS but it may take 4-6 months before a benefit can be demonstrated.
Growth factors
In MDS patients with a relatively isolated anemia, a red cell stimulant, either Erythropoietin or Darbepoietin, given by injection once weekly, will alleviate the anemia for a period of time, in 25-50% of cases.6 In patients with a relatively isolated low platelet count, a similar transient response rate can be seen with weekly Romiplostim injections.7 In MDS patients with serious infections associated with a low white cell count, Granulocyte-colony stimulating factor can be given to increase white cell (neutrophil) production although its effects are short-lived. All growth factor therapy is expensive, access to these agents may be limited and none have been convincingly shown to prolong survival in MDS patients.
Immunosuppression
Some MDS patients have a more “underactive” (hypocellular) bone marrow that resembles a bone marrow failure disorder called “aplastic anemia”. These patients appear to have bone marrow damage as a result of an inappropriately overactive immune system. Treatment with drugs to suppress the immune system (immunosuppression) can improve blood counts in about 30% of patients although response is typically slow, occurring over 3-6 months.8 Immunosuppressive treatment is started in hospital and includes a combination of Cyclosporine and intravenous anti-thymocyte globulin (ATGAM) (See Protocols/PPOs). The latter is associated with allergic reactions that, on occasion can be severe, and MDS patient treated with this agent are kept in hospital for about one week.
Immunomodulatory drugs (IMiDs)
Thalidomide is an oral drug that, in the past, has been associated with major birth defects when given to pregnant women. However, it has been used in a number of other conditions and has been shown to improve hemoglobin levels in about 30% of low-risk MDS patients.9 Thalidomide can cause sedation, constipation and nerve damage (neuropathy) and these side effects led to the development of Lenalidomide (Revlimid), a related drug associated with less sedation and neuropathy. Revlimid is more effective than Thalidomide, especially in MDS patients with deletion of chromosome 5q [del(5q)], and it has been licensed for use in del(5q) patients since 2008 (See Protocols/PPOs).10,11 It is rarely used outside of this unique patient subgroup and drug access, outside of a clinical trial, can be problematic for non-del(5q) MDS.
| The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use. |