Four Different Presentations of Transient Myeloproliferative Disorder.

Abstract Transient myeloproliferative disorder (TMD) develops in 10 % of the newborns with Down syndrome and resolves spontaneously by 2 – 3 month of life. It can also occur in a newborn with normal karyotype and trisomy 21 restricted to the abnormal clone in the bone marrow. We report 4 cases with TMD, who were diagnosed and followed in our institution between 2001–2005. Two newborns had normal germline karyotype but trisomy 21 in the bone marrow and two newborns had Down syndrome. Case 1: Full term phenotypically normal newborn presented with hepatosplenomegaly. WBC was 50,000/mm3 with 48% blasts. Bone marrow showed 84% blasts that were CD10, CD19, CD20, partial CD34, partial HLA-DR positive. Skin biopsy revealed normal karyotype 46 XY, but cytogenetics of bone marrow showed that 8/20 cells had 48 XY, +21, +22. Patient's counts improved by second month of life. At 7 months of age, he developed pancytopenia and bilateral temporal swelling with bony involvement. BMA showed AML (CD13+ and CD33+). He was treated with chemotherapy following CCG-2981. Currently he is 4 years old and in remission. Case 2: Full term phenotypically normal newborn presented with thrombocytopenia. WBC count was 20,000/mm3 with 5% blasts. Bone marrow aspiration showed 26% blasts that expressed CD33, CD13, CD4, Cd117, Cd56, partial HLA-DR and partial CD34. Cytogenetics of the blood was normal, however bone marrow revealed 47, XY, +21. His CBC normalized during the second month of life. Currently he is 4 years old and doing well. Case 3: Full term phenotypically normal newborn presented with respiratory distress, organomegaly and WBC: 115,000/mm3 with 60% blasts. Immunophenotype demonstrated expression of CD 45 with two populations; one CD33+, CD34 + and the other CD61+, CD42+. The karyotype of the blood and buccal smear revealed 47,XY, +21. Patient was treated with low dose ARA-C due to critical condition and WBC decreased to 20,000/mm3. During the next weeks he developed multiorgan failure (cardiorespiratory, renal and hepatic). Despite all measures he expired on Day 21 of life. Case 4: Full term baby with Down syndrome was diagnosed with AV canal and Tetralogy of Fallot during the prenatal period. Initial WBC count was 36,000/mm3 with 65% blasts. Immunophenotype was positive for CD33, CD34, CD4, CD117, partial HLA DR, partial CD13, partial CD56. The karyotype of the blood and buccal smear both revealed trisomy 21. Her clinical course was complicated by cardiac surgery, sepsis with persistent thrombocytopenia. Currently she is 6 months old with a normal CBC. Conclusion: TMD can have many variable presentations and outcomes ranging from spontaneous remission to leukemia to death. Any newborn with TMD should have cytogenetic studies and be followed up closely for development of leukemia. Clinical characteristics of newborns with TMD Patient Initial WBC/Blast % Karyotype Cytogenetics (bone marrow) Treatment Immunophenotype Outcome 1 50.000/ 48% 46 XY (skin biopsy) 48 XY, +21, +22 CCG 2981 CD 10, CD 19, CD 20, CD 34 partial, HLA DR. At leukemia CD13 and CD 34 CCR, alive (4 y) 2 20.000/26% 46 XY(peripheral blood) 47 XY, +21 supportive Low dose ARA CD 33, CD 13, CD 4, CD 7, CD 56, CD 34 partial, HLA DR partial CCR, alive (4 y) expired 3 115.000/ 60% 47 XY, +21 (buccal smear) 47 XY, +21 C x 5 days CD 33, CD 34, CD 61, CD 42 CD 33, CD 34, CD 4, CD 117, CD 56 Day 21 CCR, alive 4 36.000/65% 47 XX, +21 (buccal smear) 47 XX, +21 supportive partial, HLA DR partial, CD 13 partial. (6mo) CCR: continous clinical remission, y: year, mo: months