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Background: Patients with childhood cancer are at increased risk for the development of second cancers. Methods: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. Results: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. Conclusion: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. Methods: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry. Results: MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively. Conclusion: In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.

Patients with acute myeloid leukemia (AML) and hyperleukocytosis, defined as an initial white blood cell (WBC) count of ≥ 100 × 109/L, are often treated with leukapheresis. In this study, we have reported our experience of treating AML without leukapheresis. Methods: From November 1, 1995, to May 31, 2012, there were 74 children (≤18 years old) with de novo AML other than acute promyelocytic leukemia. Seventeen patients had an initial WBC count ≥ 100 × 109/L. Prompt chemotherapy was started within hours whereas leukapheresis was not performed. Results: The median age of the 17 patients with hyperleukocytosis was 7.4 years (range: 0–16 years), and the median initial WBC count was 177 × 109/L (range: 117–635 × 109/L). The median time between admission and initiation of chemotherapy was 4.5 hours (range: 2–72 hours) in patients with hyperleukocytosis, whereas it was 13 hours (range: 2–120 hours) in those without hyperleukocytosis. Seven patients (7/17, 41%) had one or more early complications before or during the first 2 weeks of chemotherapy. Fifteen of the 16 patients who received prompt chemotherapy achieved complete remission (93.8%), comparable with those without hyperleukocytosis (98.2%; p = 0.33). Conclusion: Children with AML and hyperleukocytosis, treated with prompt chemotherapy without leukapheresis, had minimal early morbidities.

In a previous study, we demonstrated that in vitro cell growth stimulated by human placental conditioned medium distinguished between transient leukemia (TL) and congenital acute myeloid leukemia (AML) in neonates. We then sought to determine whether the application can be expanded if in vitro cell growths are stimulated by recombinant human cytokines including granulocyte-macrophage colony-stimulating factor (rhGM-CSF), interleukin-3 (rhIL-3), stem cell factor (rhSCF) and thrombopoietin (rhTPO). Methods: Eight neonates with features indistinguishable from AML were studied. Seven patients had Down syndrome and the eighth a normal phenotype. Bone marrow or peripheral blood mononuclear cells (MNC) were cultured in the presence of rhGM-CSF + rhIL-3 + rhSCF or of rhTPO alone. After incubation, granulocyte- macrophage colony-forming units (CFU-GM)-derived colonies and clusters were scored on an inverted microscope. Colony-forming units-megakaryocyte (CFU-MK)-derived colonies were counted with an in situ CD61 immunostained dish. Liquid suspension cultures of MNC were stimulated by rhGM-CSF and/or rhTPO. Results: CFU-GM-derived colonies and clusters from bone marrow and peripheral blood MNC revealed normal patterns in seven patients. RhTPO-stimulated megakaryocyte colony formation was normal in one patient. Cytospin smears of liquid suspension cultures all showed good myeloid or megakaryocytic maturation consistent with TL rather than AML. One neonate died on the 2nd day of life, but in the seven remaining patients, blasts disappeared from the peripheral blood within 10 months. Among four patients followed long-term, one developed myelodysplastic syndrome at 21 months. This child was given tailored chemotherapy and had a disease-free survival > 20 months. Conclusion: In vitro cell growth stimulated by recombinant human cytokines can help to diagnose TL in neonates.