MDS and MPN (bone marrow disorders): Full guide

What are MDS and MPN?

Bone marrow is the soft, spongy tissue inside your bones. It makes your blood cells. Red blood cells carry oxygen. White blood cells fight infection. Platelets help your blood clot.

MDS and MPN are groups of conditions that start in the stem cells of the bone marrow. A stem cell is a young cell that can grow into any type of blood cell. In these conditions, one stem cell picks up gene changes and starts making copies of itself. Doctors call this a clone.

In MDS (myelodysplastic syndromes), the marrow is busy but makes blood cells that do not grow up the right way. Many die before they leave the marrow. This leads to low blood counts. Low red cells cause tiredness. Low white cells raise the risk of infection. Low platelets can cause bruising or bleeding.

In MPN (myeloproliferative neoplasms), the marrow makes too many of one or more types of blood cells. The three main types are polycythemia vera (too many red cells), essential thrombocythemia (too many platelets), and myelofibrosis (scarring of the marrow). A big worry with MPN is blood clots.

Doctors count MDS and MPN as types of blood cancer. That word can be scary. But many people, especially with lower-risk MDS, polycythemia vera, or essential thrombocythemia, live for many years. Some types can slowly change into a more serious condition, such as myelofibrosis or acute myeloid leukemia (AML). That is why regular checkups matter.

These conditions are most common in older adults. Most people with MDS are around 70 when it is found. MDS is sometimes linked to past chemotherapy or radiation, but most of the time there is no clear cause. You did not cause this.

Types

Lower-risk MDS

MDS that is likely to grow slowly. The main problem is usually anemia (low red blood cells). Treatment focuses on improving blood counts and quality of life.

Higher-risk MDS

MDS with more young, immature cells called blasts, or with certain gene changes. It is more likely to turn into AML. Treatment is stronger, and a stem cell transplant may be discussed.

MDS with del(5q)

A type of lower-risk MDS where part of chromosome 5 is missing. It often responds very well to a pill called lenalidomide.

Polycythemia vera (PV)

The marrow makes too many red blood cells, and often too many white cells and platelets too. The blood becomes thick, which raises the risk of clots, stroke, and heart attack. Itching after a warm shower, redness of the face, and headaches are common.

Essential thrombocythemia (ET)

The marrow makes too many platelets. Many people have no symptoms. Some have headaches, dizziness, vision changes, or burning pain in the hands and feet. The main risks are clots and, when platelets are very high, bleeding.

Myelofibrosis (MF)

Scar tissue builds up in the marrow, so it cannot make blood well. The spleen often grows large as it tries to make blood instead. It can start on its own (primary myelofibrosis) or develop years after PV or ET.

CMML and other overlap conditions

Some conditions have features of both MDS and MPN. The most common is chronic myelomonocytic leukemia (CMML), where there are too many monocytes, a type of white blood cell. These are treated in a similar way to MDS or MPN.

Therapy-related MDS

MDS that develops a few years after chemotherapy or radiation for another illness. It tends to be harder to treat, and a stem cell transplant is often discussed if you are fit for it.

Early conditions (CHIP and CCUS)

Some people have a blood cell gene change without a disease. If blood counts are normal, this is called CHIP. If counts are low but MDS is not found, it is called CCUS. Most people with these never develop MDS, but your care team may check your blood from time to time.

Tests you may have

Complete blood count (CBC) and blood smear

A CBC measures your red cells, white cells, and platelets. A blood smear is a look at your blood under a microscope. It can show cells that look abnormal.

Tests to rule out other causes

Low or high blood counts have many causes. Your care team may check vitamin B12, folate, copper, iron, kidney and liver tests, and look for infections or medicines that affect the marrow.

Bone marrow biopsy

A needle takes a small sample of marrow, usually from the back of the hip bone. You get numbing medicine first. The sample shows how the cells look, how many blasts there are, and whether there is scarring.

Chromosome tests

Tests called karyotype or FISH look for missing, extra, or swapped pieces of chromosomes in the marrow cells. These results help set your risk level.

Gene mutation tests

A blood or marrow test looks for gene changes such as JAK2, CALR, MPL, SF3B1, or TP53. These help confirm the diagnosis, predict how the disease may act, and sometimes point to a specific medicine.

Erythropoietin (EPO) level

EPO is a hormone from the kidneys that tells the marrow to make red cells. It is usually low in PV. In MDS, a lower level means red cell booster shots are more likely to work.

Ultrasound or scan of the spleen

Myelofibrosis and PV can make the spleen grow. An exam or a scan measures its size, which helps track how treatment is working.

Symptom questionnaire

In MPN, your care team may ask you to rate symptoms like tiredness, itching, night sweats, and feeling full quickly. This score helps track how you feel over time.

Risk levels and what they mean

MDS and MPN are not staged like many other cancers. Instead, doctors use risk scores. A risk score is a tool that adds up results from your tests to estimate how the condition may behave.

For MDS, the main tools are called IPSS-R and IPSS-M. They look at your blood counts, the percent of blasts in the marrow, chromosome changes, and (for IPSS-M) gene changes. The result places you in a group from very low to very high risk.

For PV and ET, the main question is the risk of blood clots. Age over 60 and a past clot are the biggest risk factors. In ET, a JAK2 gene change also adds risk.

For myelofibrosis, scores called DIPSS-plus and MIPSS70 use age, blood counts, symptoms, blasts, chromosome results, and gene changes.

A risk score is an average for groups of people. It cannot tell exactly what will happen to you. It helps your care team decide how strong your treatment should be.

MDS: lower risk

The goal is to treat low blood counts and keep you feeling well. If you have no symptoms, watching closely may be best.

MDS: higher risk

The goal is to slow the disease and, for some people, aim for a cure with a stem cell transplant.

PV: low risk

Under age 60 and no past clot. Treatment is usually phlebotomy (removing blood) and low-dose aspirin.

PV: high risk

Age 60 or older, or a past clot. A medicine to lower blood counts is usually added to phlebotomy and aspirin.

ET risk groups

Range from very low to high, based on age, past clots, and JAK2 status. Lower-risk ET may only need watching or aspirin. High-risk ET usually needs a medicine to lower platelets.

Myelofibrosis: lower risk

May only need watching, or treatment for anemia, symptoms, or a large spleen.

Myelofibrosis: higher risk

A stem cell transplant is often discussed for people who are fit enough. JAK inhibitor medicines help with symptoms and spleen size.

Disease change (progression)

Over time, PV or ET can turn into myelofibrosis, and MDS or MPN can turn into AML. Signs include new tiredness, falling counts, a growing spleen, or night sweats. Regular blood tests help catch this early.

Gene and lab tests to know

Gene changes in the abnormal blood cells help confirm the diagnosis and guide treatment. These are changes in the bone marrow cells only. Most are not passed down in families.

In a small number of people with MDS, a gene change is inherited. If you have family members with blood problems, or you are young, ask whether you need testing. This also matters if a family member may be a stem cell donor.

JAK2

The most common gene change in MPN. It is found in almost everyone with PV and in about half of people with ET or myelofibrosis. In ET, it raises the risk of clots.

CALR

Found in some people with ET or myelofibrosis. People with ET and a CALR change tend to have a lower clot risk than those with JAK2. But they may bleed more if platelets get very high.

MPL

A less common change in ET and myelofibrosis. It affects the signal that tells the marrow to make platelets.

Triple-negative

No JAK2, CALR, or MPL change is found. In myelofibrosis, this can mean a more serious course. Other tests are used to confirm the diagnosis.

SF3B1

A change often seen in MDS with ring sideroblasts (red cells with iron rings). It usually means a better outlook. This type often responds to a medicine called luspatercept.

del(5q)

Loss of part of chromosome 5. In lower-risk MDS, it often responds well to lenalidomide.

TP53

A change that makes MDS harder to treat, especially when both copies are affected. Your care team may discuss a stem cell transplant sooner or a clinical trial.

IDH1 and IDH2

Changes that can be targeted with specific pills. Ivosidenib is approved for MDS with an IDH1 change that has come back or not responded.

High-risk changes (ASXL1, EZH2, SRSF2, U2AF1, RUNX1)

These changes can mean MDS or myelofibrosis may act faster. They are part of modern risk scores.

Hematocrit

The percent of your blood made up of red cells. In PV, the goal is to keep it below 45 percent, because this lowers the risk of clots.

Main treatments

Watching closely

Many people with lower-risk MDS, low-risk ET, or lower-risk myelofibrosis do not need treatment right away. You have regular blood tests and visits. Treatment starts if counts drop, symptoms appear, or the disease changes.

Transfusions and iron removal

Red cell or platelet transfusions can ease tiredness and bleeding. Many transfusions can build up too much iron in the body, which can harm the liver and heart. Medicines called iron chelators remove extra iron.

Red blood cell boosters (for MDS)

Epoetin and darbepoetin are shots that tell the marrow to make more red cells. Luspatercept (Reblozyl) helps red cells mature and is now a first choice for many people with lower-risk MDS who need transfusions. Imetelstat (Rytelo) is an IV medicine for people who still need transfusions after other options.

Lenalidomide (for MDS with del(5q))

A pill that works very well in lower-risk MDS with the del(5q) change. Many people stop needing transfusions. It can lower blood counts and raise the risk of clots, so you will be checked often.

Hypomethylating agents (for higher-risk MDS)

Azacitidine (shots or IV) and decitabine (IV or a pill form called Inqovi) help the marrow work better and slow the disease. They are given for a few days each month. It often takes several months to see if they are working.

Phlebotomy and aspirin (for PV and ET)

Phlebotomy means removing some blood, like donating blood, to thin it out. It is used in PV to keep the hematocrit below 45 percent. Low-dose aspirin lowers clot risk in PV and many people with ET. A newer weekly shot called rusfertide can help some people with PV need fewer phlebotomies.

Hydroxyurea

A pill that lowers blood counts. It is often the first choice for high-risk PV and ET to reduce clot risk. It can also shrink the spleen in myelofibrosis. It should not be taken during pregnancy.

Interferon (ropeginterferon)

A shot given every few weeks that calms the overactive marrow in PV and ET. It can lower the amount of JAK2-changed cells over time. It is often chosen for younger people and is the preferred option during pregnancy.

JAK inhibitors

Pills that block the overactive JAK signal. Ruxolitinib (Jakafi) shrinks the spleen and eases symptoms in myelofibrosis, and helps PV when hydroxyurea does not. Fedratinib, pacritinib (for very low platelets), and momelotinib (for anemia) are other choices. They ease symptoms but do not cure the disease.

Stem cell transplant

An allogeneic transplant uses stem cells from a donor to replace your marrow. It is the only treatment that can cure MDS or myelofibrosis. It has serious risks, so it is mainly for higher-risk disease in people healthy enough for it. Ask your care team early if it might fit you.

Common side effects and what helps

Low blood counts

Many treatments, including azacitidine, lenalidomide, and JAK inhibitors, can lower blood counts, especially at first. Your care team checks your blood often and may pause or change the dose.

Infections

Low white cells make infections more likely. Wash your hands often, avoid people who are sick, and keep up with vaccines your care team suggests. Call right away for a fever.

Fatigue

Tiredness from anemia or treatment is very common. Short walks, regular sleep, and pacing your day can help. Tell your care team, because a transfusion or treatment change may help.

Itching (pruritus)

Itching, often after a warm bath or shower, is common in PV. Cooler showers, gentle moisturizers, and patting skin dry may help. Medicines such as antihistamines, light therapy, or ruxolitinib can also help.

Hydroxyurea effects

Can cause low counts, mouth sores, skin changes, and, rarely, leg ulcers. Use sunscreen and get regular skin checks. Tell your care team about any sore that will not heal.

Interferon effects

Can cause flu-like symptoms, tiredness, and mood changes such as depression. Taking it at bedtime may help. Tell your care team about any mood changes, sadness, or thyroid symptoms.

JAK inhibitor effects

Can cause low counts, shingles, weight gain, and a higher risk of skin cancer. Do not stop ruxolitinib suddenly, because symptoms can come back fast. Fedratinib can affect vitamin B1 (thiamine), so your levels will be checked.

Nausea, constipation, and injection site reactions

These are common with azacitidine and decitabine. Anti-nausea medicine, fluids, fiber, and a stool softener often help. Warm or cool packs can ease redness where the shot was given.

Iron overload

Many red cell transfusions can build up iron. Your care team tracks your ferritin level. Iron chelators can cause stomach upset or kidney changes, so you will have regular blood tests.

Living with MDS or MPN

For most people, MDS and MPN are long-term conditions. You may have regular blood tests for many years. Keeping a record of your counts and symptoms can help you notice changes.

Lowering clot risk is a big part of living with PV and ET. Do not smoke. Work with your primary doctor to control blood pressure, cholesterol, diabetes, and weight. Stay active and drink enough fluids, especially on long trips.

Tell every doctor and dentist about your condition and medicines. Ask before taking pain relievers like ibuprofen, especially if your platelets are low or you take aspirin. If you have surgery, your care team may need to plan around blood counts and clot risk.

If you want to become pregnant, talk with your care team first. Some medicines, like hydroxyurea, are not safe in pregnancy. PV and ET need special care during pregnancy, often with aspirin and sometimes blood thinner shots.

Fatigue and worry are common. Gentle exercise, good sleep, and talking with others can help. Ask about social workers, counseling, and support groups.

Caregivers help with rides, transfusion visits, and noticing changes. Several groups offer free information and support. These include the MPN Research Foundation, the MDS Foundation, and Blood Cancer United (formerly the Leukemia and Lymphoma Society).