RAEB: Refractory Anemia With Excess Blasts

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Refractory anemia with excess blasts, or RAEB, refers to a disorder of the blood-forming cells. RAEB is one of seven types of such disorders, or myelodysplastic syndromes (MDS), recognized by the World Health Organization (WHO) classification, which distinguishes between two categories of RAEB: RAEB-1 and RAEB-2.

Both forms generally carry a difficult prognosis: published average survival times (now dated) range from 9-16 months.

 RAEB is also associated with a heightened risk of progression to acute myeloid leukemia—a cancer of the blood-forming cells of the bone marrow.

Understanding RAEB, a Type of MDS

Myelodysplastic syndrome, or MDS, refers to the family of rare diseases of the blood in which the bone marrow does not produce enough healthy red blood cells, white blood cells or platelets. RAEB is a relatively common type of MDS, and unfortunately, it is a higher-risk form of MDS.

Like other forms of MDS, RAEB usually affects people who are over the age of 50, but it can occur in younger individuals, as well, and its cause is currently unknown.

When a person has a form of MDS such as RAEB, the bone marrow may produce many underdeveloped, or immature, cells that often have odd shapes, sizes or appearances, compared to the healthy ones. These early, juvenile, versions of blood cells are called blast cells—a term that is used quite often in the discussion of leukemia.

Indeed, today many scientists view MDS as a form of blood and bone marrow cancer.

Different classification systems have been used for these disorders. The WHO classification system attempts to sort out the types of MDS, with attention to the prognosis for a given disorder. WHO currently recognizes 7 types of MDS, and together RAEB-1 and RAEB-2 account for about 35-40 percent of all cases of MDS.

  • Refractory cytopenia with unilineage dysplasia (RCUD)
  • Refractory anemia with ringed sideroblasts (RARS)
  • Refractory cytopenia with multilineage dysplasia (RCMD)
  • Refractory anemia with excess blasts-1 (RAEB-1)
  • Refractory anemia with excess blasts-2 (RAEB-2)
  • Myelodysplastic syndrome, unclassified (MDS-U)
  • Myelodysplastic syndrome associated with isolated del(5q)

These above names often refer to how the blood and the bone marrow cells appear, when examined under the microscope. The last name in the above list, however, is defined by a certain mutation, or chromosome change, in the genetic material of the blood-forming bone marrow cells.

In the case of RAEB (both types) the name has two parts: the refractory anemia; and the excess blasts. Anemia, in general, is a lack of enough healthy red blood cells. Refractory anemia means that the anemia is not due to any of the known common causes of anemia, and that anemia generally only is corrected with blood transfusions. When a person has refractory anemia and tests reveal a greater number of immature blast cells than is normal, it is a refractory anemia with excess blasts.

It is possible for a person with RAEB to have low counts in the other cells formed by the bone marrow, too.

People with RAEB may have refractory anemia (low red blood cells), refractory neutropenia (low neutrophils), refractory thrombocytopenia (low platelets), or a combination of the three.

RAEB Is a High-Risk Form of MDS

For patients diagnosed with MDS, it is important to determine the level of risk. Some forms of MDS are low-risk, others intermediate-risk, and others high-risk. Both RAEB and RCMD are considered high-risk forms of MDS. Still, not all patients with RAEB have the same prognosis. Other factors come into play, such as age, overall health, features of the disease, and the genetics of the involved bone-forming cells.


When an MDS is suspected, a bone marrow biopsy and aspirate should be performed. This involves obtaining samples of the bone marrow and sending them to the laboratory for analysis and interpretation.

The diagnosis is made based on how the cells appear under the microscope, how they become stained with different sets of dyes and markers that involve the use of antibodies as tags, and, in the case of more advanced subtypes of MDS, something called flow cytometry. Flow cytometry is a technique that allows cells with particular characteristics to be identified and sorted out from the greater population of cells in a given sample.

Types of RAEB

Both forms (1 and 2) of RAEB are associated with the risk of progressing to acute myeloid leukemia (AML). Additionally, a patient with high-risk MDS such as RAEB may succumb to bone marrow failure, without progression to AML, and so the condition is often life threatening on its own, without progression to leukemia.

RAEB-Related Terminology:

RAEB classification depends on an understanding of several terms:

  • Bone marrow blast count: A sample of your bone marrow is obtained, and the number of abnormal, immature blast cells is measured.
  • Peripheral blood blast count: A sample of your blood from a vein is drawn using a needle, and the number of abnormal, immature blast cells is measured.
  • Auer rods: This is something the doctors will look for when they see your blasts under the microscope. Even though they are called Auer "rods," they actually come in many different shapes and sizes. They are small—smaller than the nucleus, and they are found inside the cytoplasm. Often they are needle-shaped with pointed ends, but they can be comma-shaped, diamond-shaped, or long and more rectangular.

Based on the presence or absence of the above findings, a person is determined to have either RAEB-1 or RAEB-2 as follows:

Patients are diagnosed with RAEB-1  if they had either (1) a bone marrow blast count between 5 and 9 percent of at least 500 cells counted or (2) a peripheral blast count between 2 and 4 percent of at least 200 cells counted, and (3) absent Auer rods. The presence of either criterion 1 or 2 plus 3 classifies an MDS case as RAEB-1.

The chances of RAEB-1 turning into acute myeloid leukemia are estimated at about 25 percent.

Patients are diagnosed with RAEB-2  if they had either (1) a bone marrow blast count between 10 and 19 percent of at least 500 cells counted or (2) a peripheral blast count between 5 and 19 percent of at least 200 cells counted, or (3) Auer rods detectable. The presence of either criteria 1, 2 or 3 classifies an MDS case as RAEB-2.

It is estimated that the chances of RAEB-2 turning into acute myeloid leukemia may be as high as 33 to 50 percent.​

What Is RAEB-T?

You may encounter the phrase "refractory anemia with excess blasts in transformation," or RAEB-T. This term has actually been abandoned in the current WHO-classification of myelodysplastic syndromes.

Most patients previously belonging to this category are now classified as having acute myeloid leukemia. In a different classification system, the French-American-British (the FAB-classification), patients had been assigned to the RAEB-T category if they had either (1) a bone marrow blast count between 20 and 30 percent, (2) a peripheral blast count of at least 5 percent, or (3), Auer rods detectable, irrespective of the blast count.

There continues to be some controversy regarding the value of categorizing RAEB-T as in the FAB system, separately from "AML-20-30," as in the WHO system. Several large clinical trials in recent years have used the term RAEB-T, despite the changes in the WHO classification system. The bottom line for patients and health care providers seems to be that it may be important to know that there is overlapping terminology, so as not to miss out on an opportunity to enroll in a clinical trial.

How Is RAEB Treated?

The treatment of RAEB differs for differing scenarios. The age and overall health of the individual may factor into such treatment decisions. Patients with RAEB should receive updates to their immunizations, and smokers with RAEB are encouraged to stop smoking. Signs that the RAEB may be progressing include frequent infections, abnormal bleeding, bruising, and the need for more frequent blood transfusions.

Not all patients with MDS require immediate treatment, but patients with symptomatic low counts (anemia, thrombocytopenia, neutropenia with recurrent infections) do, and this includes most patients with high or very high risk MDS (including RAEB-2, which represents the highest grade of MDS with the poorest prognosis).

Practice Guidelines of the National Comprehensive Cancer Network (NCCN) incorporate an individual's overall health and performance, the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R) MDS risk categories, and other disease characteristics to help guide management decisions. There is no “one size fits all” approach to treatment for individuals with RAEB, however.

There are generally three categories of treatment: supportive care, low intensity therapies, and high intensity therapies. These treatments are explained below:

  • Supportive care includes antibiotics for infections and red cell and platelet transfusions for symptomatic low counts.
  • Low intensity therapies include blood cell growth factors, other agents such as azacitidine and decitabine, immunosuppressive therapy, and low intensity chemotherapy. These treatments can be delivered on an outpatient basis and can improve symptoms and quality of life, but they do not cure the condition.
  • High intensity therapies include intensive combination chemo and allogeneic bone marrow transplant. These therapies require hospitalization and run the risk of life-threatening side effects, but they also may be able to improve blood counts more quickly than less intensive therapy, and may change the way the condition would normally proceed. Only certain individuals are candidates for high intensity therapies.

Clinical trials are also an option for some patients. Not too long ago, in fact, there was a clinical trial showing benefits with decitabine, compared with best supportive care, in older patients with anemia with excess blasts in transformation (RAEBt).

A Word From Verywell

If you have been diagnosed with RAEB-1, RAEB-2, or you have another type of MDS that would be considered high-risk, talk to your healthcare team about your options.

For patients with higher-risk MDS, azacitidine (5-AZA, Vidaza) and decitabine (Dacogen) are two drugs approved by the FDA for MDS that the team in charge of your care may consider. These drugs are so-called hypomethylating agents.

Several consensus groups have indicated that, for higher-risk MDS, allogeneic HSCT (bone marrow transplant) or therapy with hypomethylating agents should be initiated immediately. Allogeneic HSCT (bone marrow transplant from a donor) is the only potentially curative approach to MDS, but, unfortunately, it is a realistic option for far too few patients, owing to the older age group affected by MDS, with co-occurring chronic health conditions and other patient-specific factors.


Becker H, Suciu S, Rüter BH, et al. Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Ann Hematol. 2015 Dec;94(12):2003-13.

Germing U, Strupp C, Kuendgen A, et al. Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals. Br J Haematol. 2006;132(2):162-7.

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Jiang Y, Dunbar A, Gondek LP, et al. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood. 2009;113(6):1315-1325. 

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