Myelodysplastic Syndromes (MDS): A Plain-Language Guide

This page is for people with myelodysplastic syndromes (MDS) and their families. It explains the marrow report, how risk is scored, and the main treatments.

In myelodysplastic syndromes, the bone marrow makes blood cell precursors (young cells that should grow into blood cells) that do not mature into healthy blood cells.

That explains a finding that confuses people. NCI notes the marrow is usually full of cells (hypercellular) at diagnosis, while blood counts are low.

MDS is not one disease. It is a family of them. Different subtypes lower different types of blood cells, and their behavior varies widely. Take two subtypes:

• Refractory anemia is the mildest form. It makes up 20 to 30 percent of cases. Median survival (the time by which half of people have died) runs 2 to 5 years, and it rarely turns into leukemia.
• Refractory cytopenia with multilineage dysplasia is about 24 percent of cases. It turns into acute leukemia in 11 percent. Median overall survival is 33 months.

Dysplasia means abnormally formed. The pathologist counts how many precursor cells look wrong, and in which cell lines. Ring sideroblasts are one specific finding. These are red cell precursors with iron trapped in a ring around the nucleus. Some subtypes require at least 15 percent of red cell precursors to be ring sideroblasts. This figure comes from the National Cancer Institute’s “Myelodysplastic Syndromes Treatment (PDQ).”

The marrow also goes for chromosome analysis. Losing part of chromosome 5 is written del(5q). It is one of the findings that matters most, because it changes which drug is used.

The single most important number on an MDS marrow report is the blast percentage. Blasts are the most immature marrow cells.

When blasts reach or exceed 20 percent, the diagnosis is no longer MDS. It is acute myeloid leukemia, and treatment changes accordingly. A rising blast count on serial marrows is therefore watched closely, not just noted. This figure comes from the National Cancer Institute’s “Myelodysplastic Syndromes Treatment (PDQ).”

MDS treatment splits at "lower risk" versus "higher risk," and that split comes from a formal score.

The IPSS (International Prognostic Scoring System) combines three items:

• The marrow blast percentage
• The number of low blood counts
• The chromosome risk group

The IPSS-R is the revised version. It gives more weight to the chromosome findings and to how severe each low count is. It also reweights the blast percentage.

Both are meant to be used only at diagnosis. The WPSS is different. It is dynamic. A person can be moved between categories as the disease shifts. MD Anderson has published two more systems. One is aimed at lower-risk patients.

Ask which score your team used, what your category is, and what that category means for the goal of treatment.

Here treatment is not trying to cure. It is trying to keep you off transfusions and out of trouble.

Erythropoiesis-stimulating agents (ESAs) are lab-made versions of erythropoietin, the kidney hormone that tells the marrow to make red cells. Response depends on two things. One is your baseline erythropoietin level. The other is how much you are already being transfused. People who are anemic but not yet transfusion dependent respond best.

Luspatercept (Reblozyl) is a different mechanism. It helps late-stage red cell precursors mature. Its label covers adults with very low to intermediate risk MDS who have not had an ESA and who may need regular red cell transfusions, and some adults with ring sideroblasts whose anemia did not respond to an ESA and who need 2 or more red cell units over 8 weeks. It is an injection under the skin once every 3 weeks. The starting amount is worked out from your weight by the hematology team. They then move it up or down according to your hemoglobin, so there is no figure here for you to act on.

Lenalidomide is for del(5q). One study enrolled 148 transfusion-dependent lower-risk patients with del(5q). Of those, 67 percent became transfusion independent. The median time to response was 4 to 5 weeks. Lenalidomide is a capsule taken at home. A later trial used either a lower amount every day of a 28-day cycle or a higher amount on the first 21 days of the cycle. Teams tailor both the strength and the on-off pattern to each person's counts, so your own prescription may differ from the trial pattern.

Transfusions carry their own long-term issue. Each unit of red cells adds iron the body cannot get rid of. Iron chelation drugs bind it and carry it out. Some panels advise chelation for people with heavy ongoing transfusion needs. But its effect on survival and on disease progression is not known. That gap is worth naming.

For IPSS intermediate-2 and high-risk disease, the drugs that matter are azacitidine and decitabine. Both are DNA methyltransferase inhibitors (hypomethylating agents). They strip chemical tags off DNA. Silenced genes can then switch back on.

Two practical points follow. First, they are slow. For azacitidine, the median was 3 cycles before a first blood response. Ninety percent of responders showed something by 6 cycles. For decitabine the median was 2.2 cycles. So no change after one cycle does not mean the drug has failed. Ask your team how many cycles they plan before judging the response.

Second, azacitidine changes survival in higher-risk disease, not just counts. One phase III trial compared it with conventional care. Median overall survival was 24 months with azacitidine and 16 months without. Two-year survival was 51 percent versus 26 percent. It is given for 7 days in a row, at an amount calculated from your body size by the team giving it.

Allogeneic stem cell transplant, using cells from a donor, is the only potentially curative treatment for MDS. Its serious side effects and risk of death limit how widely it can be used. Reduced-intensity conditioning (RIC) uses gentler treatment before the transplant. It has opened the door for older adults. One study looked at 1,333 patients aged 50 and older who had allogeneic transplants for MDS. Of those, 62 percent had RIC. Both RIC and more advanced disease at transplant were linked to higher relapse.

That is the real trade-off to discuss: gentler conditioning is survivable for more people, but it lets more disease come back.

Call 911 or go to an emergency department straight away for:

• Chest pain, or breathlessness at rest.
• Sudden confusion, or a sudden severe headache.
• Bleeding that will not stop.

Call your team immediately, day or night, for:

• Temperature 100.4 F (38 C) or higher. A low neutrophil count makes infection dangerous fast, and fever may be the only sign.
• Bruising with no injury, tiny red skin dots, nosebleeds, or bleeding gums.
• New black or bloody stools.

Acute Myeloid Leukemia (AML), Stem Cell Transplant, and Leukemia.

• https://www.cancer.gov/types/myeloproliferative/hp/myelodysplastic-treatment-pdq
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=82f4d266-3f52-41eb-86ba-0abf3cf468e8
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html