Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Case presentationsCase 1A 3-year-old boy presented with a leukocyte count of 5.9 3 10 9 /L and was found to have near-haploid B-lineage acute lymphoblastic leukemia (ALL) with a 27, X, 1Y, 113, 118, 121 karyotype.He was enrolled in the St. Jude Children's Research Hospital Total Therapy XV study.After 19 days of remission induction therapy with 1 high dose of methotrexate, 14 days of prednisone, 2 doses of vincristine and daunorubicin, and 6 doses of Escherichia coli-derived asparaginase, flow cytometry examination of his bone marrow revealed the presence of minimal residual disease (MRD) amounting to 3 leukemic cells per 10 000 mononucleated cells (0.03%).Upon completion of the remaining remission induction therapy consisting of 1 dose of cyclophosphamide, 14 days of mercaptopurine, and 8 onceper-day doses of cytarabine, he attained a morphologic remission on day 46, with undetectable (,0.01%)MRD by flow cytometry and polymerase chain reaction.Because of the near-haploid ALL karyotype and negative day 46 MRD, he was assigned to receive intensive chemotherapy for 3 years.MRD remained undetectable throughout treatment.He has remained in continuous complete remission for 11.6 years. Case 2A 9-year-old boy presented with a 3-month history of progressive pallor and upper respiratory tract infection.He had no hepatosplenomegaly or mediastinal mass.An abnormal blood count with hemoglobin 3.4 g/dL, leukocytes 4.2 3 10 9 /L with 15% neutrophils, 52% lymphocytes, 33% blasts, and platelets 123 3 10 9 /L prompted a bone marrow examination which disclosed 96% replacement with leukemic lymphoblasts.By flow cytometry, the blasts expressed CD45, surface CD3, CD2, CD7, T-cell receptor g/d, CD11b, and CD13, with a subset of cells positive for CD56, a cell profile indicative of T-cell ALL.He was enrolled on the Total Therapy XV study and began remission induction therapy with high-dose methotrexate followed by prednisone once per day, vincristine once per week, daunorubicin once per week, and E coli-derived asparaginase 3 times per week.On day19 of treatment, 62.9% of bone marrow mononucleated cells were leukemic lymphoblasts by flow cytometry (31% of all cells were blasts by morphology).Three additional doses of asparaginase were given, and the remaining remission induction therapy consisted of cyclophosphamide, mercaptopurine, and cytarabine.On day 46, he attained morphologic remission (with 3% lymphoblasts), but MRD by flow cytometry was 5.82%.After consolidation treatment with 4 courses of high-dose methotrexate plus mercaptopurine as well as 1 course of re-intensification therapy with dexamethasone, etoposide, high-dose cytarabine, and asparaginase, MRD decreased to 0.18%.He attained MRD-negative status (,0.01%) after a second course of re-intensification treatment and subsequently underwent a matched-related allogeneic hematopoietic stem cell transplantation.He has remained in continuous complete remission for 11.9 years.