Symposium on Advances in Hematology
Myelodysplastic Syndrome V. Tilak, D.D. Sookmane, V. Gupta1 and J. Shukla Departments of Pathology and 1Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
ABSTRACT Pediatric myelodysplastic syndrome (MDS), though rare, constitutes a distinct entity quite different from adult MDS. They have unique clinical features, aggressive clinical course with an overall mean survival of only 9.9 months. A pediatric approach to the WHO classification has become necessary since the WHO classification of MDS has failed to address the uniqueness of pediatric MDS. A new prognostic system also needs to be evolved since the international prognostic system has limited prognostic impact in children. Intensive chemotherapy such as the one used in de novo –acute myeloid leukemia (AML) leads to complete remission in some children and this may be the treatment of choice in pediatric MDS. [Indian J Pediatr 2008; 75 (7) : 729-732] E-mail :
[email protected] Key words : Myelodysplastic syndrome; Acute myeloid leukemia, Refractory anemia
The myelodysplastic syndrome (MDS) represents a spectrum of stem cell malignancies that manifest dysplastic and ineffective hematopoiesis, which is associated with a variable risk of transformation to acute leukemia. MDS should exclude cases of low blast count leukemias that show one of the following AML type cytogenetic abnormalities: t (8; 21), inv (16), t (15; 17), 11q23.1 In comparison to MDS encountered in adults and elderly, pediatric MDS is relatively rare and their occurrence in childhood is limited to a few case reports.2,3,4 They account for 1 to 5.5 % of all pediatric hematological malignancies.5 There is overall male predominance (4:3).2,6 It is now becoming increasingly apparent that the natural history of childhood/adolescent MDS differs substantially from that of their adult counterparts. A significant number of pediatric MDS are associated with constitutional genetic abnormalities accounting for differences in treatment response and overall outcome7. The predisposing conditions for childhood MDS have been presented in table 1.8 CLASSIFICATION The WHO classification of MDS9 is based on review of adult cases. Pediatric MDS is a unique entity which differs in many ways from adult MDS (Table 2). In addition there
Correspondence and Reprint requests : Dr. Vijai Tilak, Reader, Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi – 221005. Tel. 91-9415447682. [Received May 27, 2008; Accepted May 27, 2008]
Indian Journal of Pediatrics, Volume 75—July, 2008
TABLE 1. Predisposing Conditions for Childhood MDS8 Constitutional conditions Congenital bone marrow failure • Fanconi anemia • Kostmann syndrome • Shwachman-Diamond syndrome • Blackfan-Diamond anemia Trisomy 8 mosaicism Familial MDS (at least one first degree relative with MDS/AML) Associated conditions • Prior chemotherapy /radiation, Aplastic anemia
is no data to indicate whether the blast threshold of 20% is better than the traditional 30% to distinguish MDS from AML in children.8 The WHO classification has thus failed to address the uniqueness of childhood MDS. To overcome the drawbacks of the WHO classification, Hasle et al have proposed a pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases which emphasizes the subtypes of MDS found in children, eliminating adult subtypes that are rare or unseen. The classification recommends recording of pre-existing related conditions, whether congenital, acquired, or iatrogenic. (Table 3 and 4). In brief the recommendations have been as follows: 1. Refractory cytopenia (RC) may be a more appropriate term than refractory anemia since anemia is not always present. 2. The term Refractory anemia with excess blasts in transformation (RAEB-t) may be retained for cases with 20-30% blasts in the marrow until more data are available. 3. Patients with 20-30 % blasts in the marrow with significant hepatosplenomegaly and increased WBC 729
V. Tilak et al are suggestive of AML. If patients with the aforesaid blast percentage have no clinical or cytogenetic changes characteristic of MDS or true de novo AML then a repeat BM examination 2 weeks later should be done. If blast % has increased to above 30% the patient most likely has true de novo AML. If the blast count is stable an arbitrary period of 4 weeks is suggested before establishing a diagnosis of RAEB-T. 4. The dysplastic prodrome of AML in Down syndrome is classified within myeloid leukemia in Down syndrome and excluded from population –based studies of MDS However the pediatric approach to the WHO classification fails to segregate RAEB-T into separate category, fails to accommodate syndromes other than Down syndrome, fails to address dysplasia; and retains high blast threshold of 30% required for diagnosis of AML. In addition because of strict diagnostic criteria it may miss atypical cases of MDS, myeloproliferative disease.7 CLINICAL FEATURES Most children with MDS present with nonspecific
symptoms as a result of pancytopenia, including pallor, fatigue, bruising, petechiae, and infections. However there are certain unique clinical features of paediatic TABLE 3. Diagnostic Categories of Myelodysplastic and Myeloproliferative Diseases in Children8 I. Myelodysplastic/Myeloproliferative disease • Juvenile myelomonocytic leukemia (JMML) • Chronic myelomonocytic leukemia (CMML) (secondary only) • BCR-ABL-negative chronic myeloid leukemia (Ph- CML) II. Down syndrome (DS) disease • Transient abnormal myelopoiesis (TAM) • Myeloid leukemia of DS III. Myelodysplastic Syndrome (MDS) • Refractory cytopenia (RC) (PB blasts
