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Advances in the Treatment of Myelodysplastic Syndromes

Leukemia Insights - Summer 2010

The myelodysplastic syndromes (MDS) include a very heterogeneous group of myeloid disorders characterized by ineffective hematopoiesis and transformation to acute myelogenous leukemia (AML). We find that a significant fraction of patients referred to the program come not only to discuss or receive advanced therapies but also for confirmation of their diagnosis. 

The main problem that physicians face when initially approaching a patient with MDS is the difficulty in establishing a morphological diagnosis. For instance, in approximately 30% of patients referred to our center, there is a discrepancy between the diagnosis at the time of referral and the final diagnosis. A referral to MD Anderson offers access to expert dedicated hematopathologists that focus exclusively on the diagnosis of leukemia and MDS.

Furthermore, molecular diagnostic tools including conventional cytogenetics but also genetic analysis of alterations of genes such as Ras, Flt-3 and JAK2 (among several) are now part of the standard evaluation of a patient with MDS at MD Anderson.

Once the diagnosis is established and confirmed, the next step is to predict the prognosis of an individual patient. Although tools such as the IPSS score are universally used, most investigators agree that these scores are not precise enough for patients with MDS, particularly for those patients in the lower risk categories. Other more recent models such as the WPSS score1 require information, such as WHO diagnosis criteria or number of prior transfusions, which may not be readily available to many clinicians. Investigators at MD Anderson have developed new scoring systems for all categories of patients with MDS that allow for precise prediction of survival and transformation to AML.

Table 1 summarizes the Global MD Anderson MDS Score2. This model was recently validated by independent investigators at ASH 2009. Use of this model and the MD Anderson Lower-Risk Specific Model3 enable decisions of when and in who to initiate therapy as well as how intense the therapy should be. The use of these tools thus allows for an individualized approach for patients with MDS.

In this Leukemia Insights, we summarize current therapeutic approaches to patients with MDS at our center. If you have any questions about patients with MDS or any trial in particular, please do not hesitate to contact Dr. Guillermo Garcia-Manero at ggarciam@mdanderson.org or any of the Leukemia physicians for further information. A complete list of all trials currently available to patients with MDS at MD Anderson Cancer Center is available online

Table 1: Global MD Anderson MDS Score

FactorsValue/RangesAssigned Points
Performance Status
(Zubrod)
0 or 1
≥2
0
2
Age (years)<60
60-64
≥65
0
1
2
Platelets (K/uL)<30
30-49
50-199
≥200
3
2
1
0
Hemoglobin (G/DL)<12.0
≥12.0
2
0
Marrow Blast (%)<5
5-10
11-29
0
1
2
White Blood Count (K/uL)≤20
>20.0
0
2
Karyotype-7, del(7)q or complex (>3 abn)
All Others
3
0
Prior Transfusion (RBC or PLT)No
Yes
0
1
TotalLow
Int-1
Int-2
High
0-4
5-6
7-8
>9

 

References

  1. Malcovati L, Germing U, Kuendgen A, et al. Timedependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25:3503-3510.
     
  2. 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. 2008;113:1351-1361.
     
  3. Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22:538-543.

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