Myeloproliferative disorder (MPD) is a rare complication in individuals with Noonan syndrome (NS) and an RIT1 pathogenic variant; only three cases have previously been reported. However, this condition can be life-threatening. In the present case, a neonate with a massive capillary leak and compromised general condition caused by aggressive MPD, we employed cytoreductive chemotherapy using low-dose cytarabine, which proved to be a valuable therapeutic intervention. For patients presenting with suspected MPD and exhibiting features associated with NS early in life, genetic testing that includes sequencing of RIT1 may confer significant benefits to diagnosis and disease management.

Background: The present study aimed to examine the effect of magnesium (Mg) supplementation on cisplatin-induced nephrotoxicity (CIN) in pediatric cancer patients. Methods: The present phase II, open-label, multicenter, randomized controlled trial enrolled patients aged less than 20 years who were scheduled to receive cisplatin-containing chemotherapy and randomly allocated them at a ratio of 1:1 to a Mg supplementation arm with even-numbered chemotherapy courses (arm AB) or another arm with odd-numbered courses (arm BA). Analysis objects were reconstructed into two groups depending on whether the chemotherapy course had Mg supplementation (group B) or not (group A). The primary outcome was the proportion of chemotherapy courses resulting in elevating serum creatinine per chemotherapy course. The secondary outcomes included efficacies evaluated using other biomarkers and the safety of the Mg supplementation. Results: Twenty-eight patients were randomly allocated to either group (16 to arm AB and 12 to arm BA). The baseline characteristics of the groups were similar. There was no significant difference in elevated serum creatinine between the groups (group A: 10% vs. group B: 6%; P=0.465), nor was any significant difference observed in other biomarkers during any chemotherapy course. The Mg value during chemotherapy was significantly higher in group B than in group A. No adverse events related to magnesium administration were observed. Conclusions: The study design, which treated a single chemotherapy course as a study object, failed to detect a statistically significant benefit of Mg supplementation for preventing CIN in pediatric cancer patients.

Background The present study aimed to identify the predictive factors of acute respiratory events (ARE), including severe hypoxia, during initial induction chemotherapy in patients with newly diagnosed advanced neuroblastoma. Method The medical records of 75 consecutive patients in whom stage III or IV neuroblastoma was newly diagnosed between January 2003 and December 2018 at two medical institutions were retrospectively reviewed. The outcome was ARE concomitant with severe hypoxia between the first and 14th days of initial induction chemotherapy. Severe hypoxia was defined as grade 3 or higher according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4.0) or decreased oxygen saturation at rest (e.g., pulse oximeter < 88% or PaO2 ≤ 55 mmHg). Possible predictive factors on admission were first screened for using univariate analyses with a P value of 0.05, then models of the predictive power of the outcome were evaluated by generating receiver operating characteristic (ROC) curves. Results Eleven patients (14.7%) had the outcome, including three (4.0%) who required respiratory support in the intensive care unit. The area under the curve of the ROC for the predictive factors screened by univariate analyses were 0.84 (95% confidence interval (CI): 0.73-0.95) for lactate dehydrogenase (LDH) and 0.90 (95% CI: 0.82-0.98) for the disseminated intravascular coagulation (DIC) score. Conclusion The LDH value and DIC score on admission may be clinically useful predictors of ARE during initial induction chemotherapy in patients with advanced neuroblastoma.

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the non-surviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (p<0.01). Moreover, achieving a second complete remission (CR2) prior to hematopoietic cell transplantation was associated with a good prognosis (p<0.01). Etoposide, cytarabine and mitoxantrone (ECM)- or fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (p<0.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (p=0.04) and core binding factor-AML, t(8;21) and inv(16), as good prognostic markers (p<0.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.