•The high-risk group is characterized by inadequate response to initial corticosteroids, cytomorphologic pattern, no complete response to treatment on day 33+, t(9;22)/BCR/ABL, t(4;11)/MLL-AF4 and MRD >103 3 months after start of treatment

2.6Characteristics and Prognosis of ALL in Infants

•Initially often high WBC, massive organ enlargement, severe thrombocytopenia, high rate of CNS involvement, poor response to treatment, and high rate of relapse in comparison with childhood ALL, particularly extramedullary relapse

•The leukemic cells of infants mainly display a more primitive phenotype (often HLA-DR antigen-positive, CD19+, CD10-negative, immunoglobulin or T cell receptor genes in germ-line configuration). Frequently involvement of chromosome 11 [11q23, MLL/AF4ALL-1 gene rearrangement, t(4;11)], simultaneous occurrence of lymphoid and myeloid markers; immunoglobulin genes often in germ-line configurations

2.7Differential Diagnosis

•Leukemoid reaction:

–Bacterial infection, acute hemolysis, tuberculosis, sarcoidosis, histoplasmosis, or metastatic tumors

–Increased WBC (up to 50 × 109/l) and/or peripheral immature granulocyte precursors

–Occurs frequently in neonates and children with trisomy 21

•Lymphocytosis:

–Pertussis and other viral infections

–Infants and small children often have physiological lymphocytosis with an incidence of approx. 85%

•Infectious mononucleosis

•Aplastic anemia:

–Pancytopenia and hypoplastic bone marrow

•Immune thrombocytopenia purpura (ITP):

–Without anemia (with exception of children with severe bleeding), normal morphology of white blood cell differentiation

•Bone marrow infiltration by a solid tumor (metastatic disorder):

–Neuroblastoma (increased level of urine catecholamines)

–Non-Hodgkin lymphoma (when >25% of blasts in the bone marrow are defined as leukemia)

–Rhabdomyosarcoma and retinoblastoma may have a similar infiltration of the bone marrow as leukemia, but usually with clusters of malignant cells

•Rheumatoid fever and rheumatoid arthritis, with similar initial symptomatology, but without alteration of peripheral blood cell count and bone marrow abnormalities