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Myelodysplastic Syndromes Treatment (PDQ®)

Pathologic and Prognostic Systems for MDS

Myelodysplastic syndromes (MDS) are classified according to features of cellular morphology, etiology, and clinical presentation. The morphological classification of MDS is largely based on the percent of myeloblasts in the bone marrow and blood, the type and degree of myeloid dysplasia, and the presence of ring sideroblasts.[1] The clinical classification of the MDS depends upon whether there is an identifiable etiology and whether the MDS has been treated previously.

Pathologic Systems

The World Health Organization (WHO) classification [2] has supplanted the historic French-American-British (FAB) classification,[1] as shown in Table 1.

Table 1. Myelodysplastic Syndromes: Comparison of the FAB and WHO Classifications
FAB (1982)WHO (2008)
AML = acute myeloid leukemia; FAB = French-American-British classification scheme; MDS = myelodysplastic syndromes; WHO = World Health Organization.
Myelodysplastic Syndromes
Refractory anemia.Refractory anemia.
 Refractory cytopenia with multilineage dysplasia. Refractory cytopenia with unilineage dysplasia.
Refractory anemia with ring sideroblasts.Refractory anemia with ring sideroblasts.
Refractory anemia with excess blasts.Refractory anemia with excess blasts -1 and -2.
 Myelodysplastic syndrome, unclassifiable.
 Myelodysplastic syndrome associated with del(5q).
 Reclassified from MDS to:
Refractory anemia with excess blasts in transformation.Acute myeloid leukemia identified as AML with multilineage dysplasia following a myelodysplastic syndrome.
Chronic myelomonocytic leukemia.Myelodysplastic and myeloproliferative diseases.

MDS cellular types and subtypes in either cellular classification scheme have different degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia, and prognoses.

Refractory anemia (RA)

In patients with RA, the myeloid and megakaryocytic series in the bone marrow appear normal, but megaloblastoid erythroid hyperplasia is present. Dysplasia is usually minimal. Marrow blasts are less than 5%, and no peripheral blasts are present. Macrocytic anemia with reticulocytopenia is present in the blood. Transformation to acute leukemia is rare, and median survival varies from 2 years to 5 years in most series. RA accounts for 20% to 30% of all patients with MDS.

Refractory anemia with ring sideroblasts (RARS)

In patients with RARS, the blood and marrow are identical to those in patients with RA, except that at least 15% of marrow red cell precursors are ring sideroblasts. Approximately 10% to 12% of patients present with this type, and prognosis is identical to that of RA. Approximately 1% to 2% of RARS evolve to acute myeloid leukemia (AML).

Refractory anemia with excess blasts (RAEB)

In patients with RAEB, there is significant evidence of disordered myelopoiesis and megakaryocytopoiesis in addition to abnormal erythropoiesis. Because of differences in prognosis related to progression to a frank AML, this cellular classification is composed of two categories: RAEB-1 and RAEB-2. Combined, the two categories account for approximately 40% of all patients with MDS. RAEB-1 is characterized by 5% to 9% blasts in the bone marrow and less than 5% blasts in the blood. Approximately 25% of cases of RAEB-1 progress to AML. Median survival is approximately 18 months. RAEB-2 is characterized by 10% to 19% blasts in the bone marrow. Approximately 33% of cases of RAEB-2 progress to AML. Median survival for RAEB-2 is approximately 10 months.

Refractory cytopenia with multilineage dysplasia (RCMD)

In patients with RCMD, bicytopenia or pancytopenia is present. In addition, dysplastic changes are present in 10% or more of the cells in two or more myeloid cell lines. There are less than 1% blasts in the blood and less than 5% blasts in the bone marrow. Auer rods are not present. Monocytes in the blood are less than 1 × 109. RCMD accounts for approximately 24% of cases of MDS. The frequency of evolution to acute leukemia is 11%. The overall median survival is 33 months. Refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS) represents another category of RCMD. In RCMD-RS, features of RCMD are present, and more than 15% of erythroid precursors in the bone marrow are ring sideroblasts. RCMD-RS accounts for approximately 15% of cases of MDS. Survival in RCMD-RS is similar to that in primary RCMD.

Refractory cytopenia with unilineage dysplasia (RCUD)

In patients with RCUD, a single cytopenia is present, involving either erythrocytes, neutrophils, or platelets. In addition, dysplastic changes are present in 10% or more of the cells in two or more myeloid cell lines. There are less than 1% blasts in the blood and less than 5% blasts in the bone marrow. Auer rods are not present. Monocytes in the blood are less than 1 × 109.

Unclassifiable myelodysplastic syndrome (MDS-U)

The cellular subtype MDS-U lacks findings appropriate for classification as RA, RARS, RCMD, or RAEB. Blasts in the blood and bone marrow are not increased.

Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality

This MDS cellular subtype, the 5q- syndrome, is associated with an isolated del(5q) cytogenetic abnormality. Blasts in both blood and bone marrow are less than 5%. This subtype is associated with a long survival. Karyotypic evolution is uncommon. Additional cytogenetic abnormalities may be associated with a more aggressive MDS cellular subtype or may evolve to AML.

Therapy-related myeloid neoplasms

The latest version of the WHO pathologic classification system identifies patients with therapy-related MDS or AML and places them in the same category as “therapy-related myeloid neoplasms.” This group of disorders evolves in patients who were previously treated with chemotherapy or radiation therapy for other cancers and in whom there is a clinical suspicion that the prior therapy caused the myeloid neoplasm. Classic chemotherapy agents associated with these disorders include alkylating agents, topoisomerase inhibitors, and purine nucleoside analogs.

Chronic myelomonocytic leukemia (CMML)

Although previously classified with the myelodysplastic syndromes, CMML is now assigned to a group of overlap myelodysplastic/myeloproliferative neoplasms. (Refer to the PDQ summary on Myelodysplastic/ Myeloproliferative Neoplasms for more information.)

Prognostic Scoring Systems

A variety of pathologic and risk classification systems have been developed to predict the overall survival of patients with MDS and the evolution from MDS to AML. Major prognostic classification systems include the International Prognostic Scoring System (IPSS), revised as the IPSS-R;[3] the WHO Prognostic Scoring System (WPSS); and the MD Anderson Cancer Center Prognostic Scoring Systems.[4,5] Clinical variables in these systems have included bone marrow and blood myeloblast percentage, specific cytopenias, transfusion requirements, age, performance status, and bone marrow cytogenetic abnormalities.

IPSS

The IPSS incorporates bone marrow blast percentage, number of peripheral blood cytopenias, and cytogenetic risk group.

IPSS-R

Compared with the IPSS, the IPSS-R updates and gives greater weight to cytogenetic abnormalities and severity of cytopenias, while reassigning the weighting for blast percentages.[3]

WPSS

In contrast to the IPSS and IPSS-R, which should be applied only at the time of diagnosis, the WPSS is dynamic, meaning that patients can be reassigned categories as their disease progresses.

MD Anderson

The MD Anderson Cancer Center has published two prognostic scoring systems, one of which is focused on lower-risk patients.[4,5]

References

  1. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982. [PUBMED Abstract]
  2. Vardiman JW, Thiele J, Arber DA, et al.: The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114 (5): 937-51, 2009. [PUBMED Abstract]
  3. Greenberg PL, Tuechler H, Schanz J, et al.: Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120 (12): 2454-65, 2012. [PUBMED Abstract]
  4. Garcia-Manero G, Shan J, Faderl S, et al.: A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 22 (3): 538-43, 2008. [PUBMED Abstract]
  5. Kantarjian H, O'Brien S, Ravandi F, et al.: Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 113 (6): 1351-61, 2008. [PUBMED Abstract]
  • Updated: December 4, 2014