Akira Shimada

Acute liver failure in the neonatal period is commonly caused by infections, metabolic disorders, immune disorders, or neonatal hepatitis-like diseases of unknown etiology; however, malignant diseases are rarely included in the differential diagnosis, and leukemia may be overlooked. We report a case of neonatal acute liver failure that required living-donor liver transplantation from the patient’s father, which was later diagnosed as acute megakaryoblastic leukemia (AMKL) harboring an RBM15::MKL1 fusion transcript. After liver transplantation, leukemic blasts infiltrated the transplanted liver, necessitating the initiation of chemotherapy. The patient achieved remission and has survived for four years after completion of reduced-intensity AML-type chemotherapy. RBM15::MKL1-positive AMKL is characteristically associated with both myelofibrosis and hepatic fibrosis. Congenital cases have also been reported, suggesting that RBM15::MKL1 AMKL may originate in the intrauterine fetal liver. A literature search for “acute liver failure” and “acute megakaryoblastic leukemia” revealed five cases reported since 2000. All patients had an RBM15::MKL1 fusion transcript and all died. In contrast, survival has been reported in patients with RBM15::MKL1-AMKL who did not present with acute liver failure. We speculate that our patient survived because acute liver failure was successfully managed with living-donor liver transplantation.

Transient abnormal myelopoiesis (TAM) occurs in 10% of neonates with Down syndrome (DS). Although most patients show spontaneous resolution of TAM, early death occurs in ∼20% of cases. Therefore, new biomarkers are needed to predict early death and determine therapeutic interventions. This study aimed to determine the association between clinical characteristics and cytokine levels in patients with TAM. A total of 128 patients with DS with TAM enrolled in the TAM-10 study conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group were included in this study. Five cytokine levels (interleukin-1b [IL-1b], IL-1 receptor agonist, IL-6, IL-8, and IL-13) were significantly higher in patients with early death than in those with nonearly death. Cumulative incidence rates (CIRs) of early death were significantly associated with high levels of the 5 cytokines. Based on unsupervised consensus clustering, patients were classified into 3 cytokine groups: hot-1 (n = 37), hot-2 (n = 42), and cold (n = 49). The CIR of early death was significantly different between the cytokine groups (hot-1/2, n = 79; cold, n = 49; hot-1/2 CIR, 16.5% [95% confidence interval (CI), 7.9-24.2]; cold CIR, 2.0% [95% CI, 0.0-5.9]; P = .013). Furthermore, cytokine groups (hot-1/2 vs cold) were independent poor prognostic factors in the multivariable analysis for early death (hazard ratio, 15.53; 95% CI, 1.434-168.3; P = .024). These results provide valuable information that cytokine level measurement was useful in predicting early death in patients with TAM and might help to determine the need for therapeutic interventions. This trial was registered at UMIN Clinical Trials Registry as #UMIN000005418.

CD25 is an aberrant marker expressed on the leukemic stem cell (LSC) surface and an immunotherapy target in acute myeloid leukemia (AML). However, the clinical prevalence and significance of CD25 expression in pediatric AML are unknown. High IL2RA/CD25 expression in pediatric AML showed a stem cell‐like phenotype, and elevated CD25 expression was associated with lower overall survival (p < .001) and event‐free survival (p < .001) in the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐05 study. This finding was reproduced in AML without a core‐binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.

Immune thrombocytopenia (ITP) is a common childhood acute autoimmune bleeding disorder caused by numerous viruses and characterized by isolated thrombocytopenia. Although cases of ITP caused by coronavirus disease 2019 (COVID‐19) infection have been reported in adults, pediatric reports are limited. We present the case of a 1‐year‐old girl who developed COVID‐19‐infection‐related ITP with a very low platelet count (0.0 × 10⁴/μL). We searched for COVID‐19‐related pediatric ITP cases and found 10 other cases, with the majority having platelet counts of 4/μL. Although pediatric ITP cases caused by COVID‐19 infection may be severe, further studies are needed.

We previously reported that risk‐stratified therapy and intensive postremission chemotherapy (PRC) contributed to the improved survival of childhood acute myeloid leukemia (AML) in the AML99 study, which led us to consider a reduction in the number of PRC courses with more restrictive indications for stem cell transplantation (SCT) in the successor AML‐05 study. We here report the outcome of AML patients without core‐binding factor mutation (non‐CBF AML) in the AML‐05 study. Two‐hundred eighty‐nine children (age < 18 years old) with non‐CBF AML were eligible. Patients with unfavorable cytogenetics and/or poor bone marrow response to the first induction course were candidates for SCT in the AML‐05 study. After two courses of induction, a further three courses of PRC were given in AML‐05, while four courses were given in the AML99 study. The 3‐year event‐free survival (EFS) rate in the AML‐05 study (46.7%, 95% CI: 40.6‐52.6%) was comparable to that of non‐CBF AML in the AML99 study (51.5%, 95% CI: 42.7‐59.6%) (P = .16). However, the 3‐year overall survival (OS) rate in the AML‐05 study (62.9%, 95% CI: 56.3‐68.8%) was slightly lower than that in the AML99 study (71.6%, 95% CI: 63.2‐78.5%) (P = .060), mainly due to decreased remission induction rate and increased nonrelapsed mortality. In conclusion, reductions in the number of PRC courses from four to three, together with repetitive cycles of high‐dose cytarabine, were acceptable for non‐CBF childhood AML.