Myelodysplastic Syndrome Treatment: medication and other options

Medically reviewed: 30, December 2023

Myelodysplastic Syndrome Treatment guideline

Myelodysplastic Syndromes (MDS) encompass a multitude of varying conditions affecting the bone marrow, leading to insufficient production of vital blood cells. This cluster of disorders is commonly known as a “bone marrow failure disorder” due to its characteristic inability to generate an adequate supply of healthy blood cells. Myelodysplastic syndromes treatment is as complex and diverse as the syndromes themselves.

The primary goal of MDS treatment is to manage symptoms, prevent complications, and improve quality of life. This can be achieved through supportive care treatments, drug therapies, and in some cases, stem cell transplantation.

Supportive care treatments aim to alleviate the symptoms of MDS, such as fatigue caused by anemia, and include blood transfusions, growth factor therapy, and iron chelation therapy. Drug therapies, on the other hand, aim to modify the course of the disease. These include hypomethylating agents, immunomodulatory drugs, and targeted therapies that specifically attack cancer cells.

In more severe cases of MDS, a stem cell transplant may be considered. This procedure involves replacing the patient’s diseased bone marrow with healthy stem cells from a donor, allowing the patient’s body to produce healthy blood cells.

It is crucial to acknowledge that the selection of treatment options is contingent upon a multitude of factors, encompassing the patient’s age, general well-being, specific type of myelodysplastic syndromes (MDS), and the likelihood of the disease advancing to acute myeloid leukemia (AML).

Therefore, treatment plans are highly individualized and tailored to meet the specific needs of each patient.

In the following chapters, we will delve deeper into each of these treatment options, discussing their mechanisms, benefits, and potential side effects. We will also explore the latest research in MDS treatment, shedding light on promising new therapies currently under investigation. Stay tuned as we navigate the complex landscape of Myelodysplastic Syndrome Treatment.

There are no formal guidelines for the treatment for Myelodysplastic Syndrome (MDS). Therapies are either conventional for all hematologic malignancies or are experimental. The therapies can therefore be categorized into supportive care, low-intensity therapy, high-intensity therapy, and bone marrow transplantation. The use of combinations of all of these therapies is not uncommon.

Myelodysplastic Syndrome Treatment and Supportive Care

Conventional therapy, or the standard of care for MDS, especially in community settings, is supportive care, including blood product transfusion and the use of hematopoietic growth factors (HGFs). G-CSF, erythropoietin (EPO), and IL-11, although not specifically approved for MDS, have been widely used in patients with cytopenia. Since the majority of patients die from infection, bleeding, and leukemia transformation, conventional therapy provides only temporary symptom relief, neither preventing disease progression nor prolonging survival.

Iron overload should be investigated if more than 20-30 units of red blood cells are transfused in transfusion-dependent patients. If the overload is severe, patients should be treated with an iron-chelating agent such as deferoxamine.

Myelodysplastic Syndrome Medication Treatment

Low-Intensity Therapy with Myelodysplastic Syndrome

Low-intensity therapy is defined as treatment with low doses of chemotherapeutic agents or biologic modifiers, based on the rationale of cytotoxic effect and/or differentiation induction.

Patients in a low-to-intermediate risk group, as evaluated by the IPSS system, are candidates for this treatment. Low-dose cytarabine has been extensively used as an outpatient treatment. It is given subcutaneously, 10-30 mg/m2/day, divided into 2 doses, for 2 to 8 weeks. Other agents such as 5-azacytidine, aclarubicin, melphalan, and decitabine are currently undergoing clinical trials.

Although some of these treatments have been associated with significant hematologic responses, there is no proven survival benefit from these drugs when used alone. Recently, low-dose chemotherapy followed by growth factors and/or all-trans retinoic acid (ATRA) has proven to be an attractive regimen for MDS treatment, with better overall response and survival prolongation reported in some nonrandomized studies.

High-Intensity Therapy with Myelodysplastic Syndromes

High-intensity myelodysplastic syndrome treatment is aimed at eradicating neoplastic clones and allowing regeneration of normal hematopoiesis, therefore providing long-term remission. This treatment, mainly consisting of intensive chemotherapy, is associated with hematologic remission and occasionally with cytogenetic remission; significant toxicity and mortality have also been reported.

Since the biology of high-risk MDS is similar to that of AML, the most commonly used regimens for MDS are acute leukemia-type chemotherapy regimens consisting of anthracycline and Ara-C, with or without topoisomerase inhibitors.

Fludarabine-containing chemotherapy as myelodysplastic syndrome treatment was also found to be as effective in MDS as are other AML- type regimens, based on the synergistic action of fludarabine and cytarabine.

A total of 50% to 60% of patients with high-risk myelodysplastic syndrome can achieve complete remission with intensive chemotherapy. However, the relapse rate is about 90% in patients with MDS, whereas the same regimen given to patients with AML achieves a 70% to 80% remission rate with a lower percentage of relapse. This disproportion suggests that MDS confers a poorer prognosis than AML due to its distinctive karyotype.

A recent study from the MD Anderson Cancer Center evaluated 394 patients with high-risk MDS. Patients were treated with 5 regimens of intensive chemotherapy, and a total of 58% achieved a complete response. The response rates of myelodysplastic syndrome with anthracycline and nonanthracycline-containing regimens are similar. However, intensive chemotherapy regimens were not associated with survival prolongation.

In general, patients with MDS who are at a high risk, especially if they are over the age of 65 years, should be recommended for aggressive therapy. Scheduled uses of HGFs with chemotherapy were found to shorten the recovery from cytopenia and to reduce chemotherapy-related mortality.

Myelodysplastic Syndrome Treatment: Bone Marrow Transplantation

Allogeneic bone marrow transplantation (ABMT) is the definitive myelodysplastic syndrome treatment. In patients with less advanced MDS (ie, patients with RA or RARS), the 3-year disease-free survival (DFS) rate ranged from 40% to 60%, with a relapse rate of 10% to 20% and a mortality rate of about 30%.

Compared with patients with MDS who are at low risk, patients with advanced MDS who underwent ABMT (ie, those with RAEB, RAEB-T, and t-MDS) had a much lower DFS rate (0% to 20%) and high relapse and mortality rate (30% to 60%).

Since the median age of MDS is between 60 and 70 years, patients who can benefit from ABMT are limited in number, which may explain the higher DFS and mortality. In addition, elderly patients usually have a lower tolerance to myeloablative treatment and total body irradiation, although a recent study suggested that allogeneic and syngeneic marrow transplantation can be successfully done in patients with MDS who are 55 to 65 years of age.

Other transplantation techniques, such as autologous bone marrow transplantation, peripheral blood stem cell transplantation, and nonmyeloablative bone marrow transplantation, are still experimental.

Myelodysplastic Syndrome: Summary of Treatment Options

The strategy of designing a myelodysplastic syndrome treatment regimen specific to each individual patient is important; physicians must balance the benefits and toxicities caused by the therapeutic regimen. Age, myelodysplastic syndrome subtype, IPSS score, and performance status all function as independent indices in the decision-making process.

In general, asymptomatic patients should be given a period of observation to monitor for disease progression.

• Patients with MDS who are at low-to-intermediate risk, with normal or relatively benign karyotypes, should be recommended for conventional therapy and/or low-intensity chemotherapy;
• patients with aggressive subtypes of MDS, multilineage cytopenia, and malignant karyotypes should be treated aggressively with high-intensity chemotherapy or bone marrow transplantation. These patients should also be encouraged to participate in clinical trials testing experimental therapies.

Young patients with high-risk myelodysplastic syndrome who demonstrate good tolerance to therapy can benefit from ABMT if matched donors are available. To date, the only curative treatment is ABMT, although intensive chemotherapy is also associated with occasional complete cytogenetic remission. Intensive therapy and bone marrow transplantation carry significant adverse effects, with considerable mortality and a risk of developing therapy-related acute leukemia and myelodysplasia, especially in elderly patients.

More clinical trials are required to explore highly effective, less toxic, and more targeted regimens for patients with MDS.

Clinical trials are essential for providing an understanding of disease pathophysiology, improved disease management, and the discovery of new treatment regimens. Myelodysplastic syndrome provides a good model for scientific investigation because of the divergent karyotypes and the paradoxic coincidence of abnormal “growth” and “death” of the hematopoietic cells.

For instance, chemotherapy primed with growth factors may accelerate the recovery of postchemotherapy neutropenia and recruit more progenitors into the cell cycle, thus making them more susceptible to Ara-C.However, this regimen may also render to leukemic cells anti-apoptotic properties.

Hence, sequential treatments with growth factors after chemotherapy or bone marrow transplantation are preferred. On the other hand, it is difficult to eliminate neoplastic clones while concomitantly improving recovery of normal hematopoietic clones with the current nonselective therapeutic agents.

Thus, developing specific, targeted therapeutic agents and reducing therapy-related toxicity, mortality, and disease relapse are currently the major goals in research and clinical studies.