Philadelphia chromosome-positive acute lymphoblastic leukemia and Down syndrome.

Children with Down syndrome (DS) are at high risk of developing acute lymphoblastic leukemia (ALL), but Philadelphia chromosome-positive (Ph+) ALL is rare in DS children. We report a case of Ph+ALL with DS complicated by chronic heart failure. Complete molecular remission was obtained after imatinib-combined chemotherapy, although infectious episodes during the neutropenic period worsened the heart condition. After two courses of intensification chemotherapy, the patient underwent reduced intensity stem cell transplantation from an HLA-identical sibling donor followed by post-transplant imatinib. The patient maintained molecular complete remission for >2 years. This case report is the first description of the safe and effective use of imatinib for DS-Ph+ALL. This case suggests the potential of molecular targeting therapy in DS-ALL, which is often complicated by congenital diseases, and the importance of treating DS-ALL while maintaining intensity and reducing treatment-related toxicity.

Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature.

Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD)10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin λ. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 × 10(9)/L). At the latest follow-up for each case (12-98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease.