A JH CME Information: Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification and management Author: Guillermo Garcia-Manero, M.D. CME Editor: Ayalew Tefferi, M.D.

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䊏 Accreditation and Designation Statement: Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Blackwell Futura Media Services designates this journal-based CME for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

䊏 Educational Objectives Upon completion of this educational activity, participants will be better able to: 1. Understand the latest updates on molecular and cytogenetic alterations in MDS. 2. Understand the latest updates on the classification and treatment of patients with MDS.

䊏 Activity Disclosures No commercial support has been accepted related to the development or publication of this activity. Author: Guillermo Garcia-Manero, M.D. has no conflicts of interest to disclose. CME Editor: Ayalew Tefferi, M.D. has no conflicts of interest to disclose. This activity underwent peer review in line with the standards of editorial integrity and publication ethics maintained by American Journal of Hematology. The peer reviewers have no conflicts of interest to disclose. The peer review process for American Journal of Hematology is single blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review. Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services’s Policy on Activity Disclosure and Conflict of Interest. The primary resolution method used was peer review and review by a non-conflicted expert.

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C 2014 Wiley Periodicals, Inc. V


American Journal of Hematology, Vol. 89, No. 1, January 2014



AJH Educational Material


Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification, and management

Guillermo Garcia-Manero* Disease overview: The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older male and in individuals with prior exposure to cytotoxic therapy. Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is complementary but not diagnostic. Risk-stratification: Prognosis of patients with MDS can be calculated using a number of scoring systems. In general, all these scoring systems include analysis of peripheral cytopenias, percentage of blasts in the bone marrow and cytogenetic characteristics. The most commonly used system is the International Prognostic Scoring System (IPSS). IPSS is likely to be replaced by a new revised score (IPSS-R) and by the incorporation of new molecular markers recently described. Risk-adapted therapy: Therapy is selected based on risk, transfusion needs, percent of bone marrow blasts and more recently cytogenetic profile. Goals of therapy are different in lower risk patients than in higher risk. In lower risk, the goal is to decrease transfusion needs and transformation to higher risk disease or AML, as well as to improve survival. In higher risk, the goal is to prolong survival. Current available therapies include growth factor support, lenalidomide, hypomethylating agents, intensive chemotherapy, and allogeneic stem cell transplantation. The use of lenalidomide has significant clinical activity in patients with lower risk disease, anemia, and a chromosome 5 alteration. 5-Azacitidine and decitabine have activity in higher risk MDS. 5-Azacitidine has been shown to improve survival in higher risk MDS. A number of new molecular lesions have been described in MDS that may serve as new therapeutic targets or aid in the selection of currently available agents. Additional supportive care measures may include the use of prophylactic antibiotics and iron chelation. Management of progressive or refractory disease: There are no approved interventions for patients with progressive or refractory disease particularly after hypomethylating based therapy. Options include cytarabine based therapy, transplantation and participation on a clinical trial. C 2013 Wiley Periodicals, Inc. Am. J. Hematol. 89:98–108, 2014. V

䊏 Disease Overview Myelodysplastic (MDS) comprises a very heterogeneous group of myeloid malignancies with very distinct natural histories [1,2]. MDS occurs in 3–4 individuals per 105 in the US population [3]. Prevalence increases with age. For instance in individuals age 60 and above, prevalence is 7–35 per 105 [3]. Other series have reported higher rates [4] but those studies were based on Medicare reporting that is not based on histopathological diagnosis. MDS affects more frequently males than females [3]. Exposure to prior chemo or radiation therapy is a risk for the development of MDS. MDS is usually suspected by the presence of cytopenia on a routine analysis of peripheral blood. This prompts evaluation of bone marrow cell morphology (aspirate) and cellularity (biopsy). A manual count of bone marrow blasts is fundamental for risk assessment. Cytogenetic analysis helps in predicting risk and in selecting therapy. Once this information is collected, the risk of the patient can be calculated. Currently, the International Prognostic Scoring System (IPSS) [5] is still the most commonly used score. Natural history and therapeutic decisions are different for patients with lower risk disease (low and INT-1) versus those with higher (INT-2 and high). In lower risk disease, interventions have been traditionally developed to improve transfusion needs; whereas higher risk options have been modeled following therapy of acute myelogenous leukemia (AML) with remission induction being the goal. This concept is being modified by the better understanding of the natural progression of MDS and the

Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas

Conflict of Interest: Nothing to report. *Correspondence to: Guillermo Garcia-Manero, MD, Department of Leukemia, MD Anderson Cancer Center, Box 428, 1515 Holcombe Blvd, Houston, TX 77030. E-mail: [email protected] Received for publication: 21 November 2013 Am. J. Hematol. 89:98–108, 2014. Published online: in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.23642 C 2014 Wiley Periodicals, Inc. V


American Journal of Hematology, Vol. 89, No. 1, January 2014



Figure 1. New cytogenetic classification of MDS. Reproduced with permission from Schanz et al. J Clin Oncol, 2012 March 10, 30(8), 820–829. Schanz et al. (Ref. 8). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

TABLE I. A Prognostic Model of Hypoplastic MDS [10] Prognostic factor


Hemoglobin < 10 (g/dl) Performance status  2 Unfavorable cytogenetics Bone marrow blast  5% Serum LDH > 600 (IU/l)

0.00026 0.00484 0.00667 0.00765 0.00990

development of new therapies. Another important concept is that a large majority of patients with MDS die from causes intrinsic to the disease and not due to progression to AML [6]. This has important implications for the development of therapies in MDS. A revised IPSS score (IPSS-R) was published in 2012 [7]. The new IPSS-R includes a new cytogenetic risk classification of the disease that divides patients into five cytogenetic categories (Fig. 1) [8]. At this point, it is unclear how the IPSS-R is going to be used in clinical practice and in drug development. It should be noted that the latest version of the American NCCN guidelines already include this prognostic model [9].

䊏 Diagnosis The diagnosis of MDS is suspected based on the presence of an abnormal CBC. Diagnosis is confirmed by performing a bone marrow aspiration and biopsy. Both procedures provide different information. The bone marrow aspirate allows for detailed evaluation of cellular morphology and evaluation of percent of blasts. The bone marrow biopsy allows for determination of bone marrow cellularity and architecture. There is some controversy regarding the utility of bone mar-


row biopsy. In my practice, we treat patients with hypocellular MDS (those with bone marrow cellularity 64 Platelets 3 109/L

Myelodysplastic syndromes: 2014 update on diagnosis, risk-stratification, and management.

The myelodysplastic (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of trans...
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