No conclusive reports indicate that renal function at diagnosis affects the subsequent clinical outcomes of pediatric patients with acute myeloid leukemia (AML). The present study aimed to determine the frequency of a decrease in estimated glomerular filtration rate (eGFR) at the diagnosis of AML in children, adolescents, and young adults (AYA) and its impact on patients’ clinical outcomes. We calculated the eGFR at diagnosis of 40 de novo AML patients aged 2 years or older and investigated the correlation between eGFR and clinical outcome. Decreased eGFR was defined as eGFR less than 90 ml/min/1.73 m2. Nine (22.5

The prognosis for pediatric hematological malignancies has improved greatly, but infectious diseases, especially invasive fungal infection (IFI), are an important complication that may make it difficult to continue treatment. In this study, IFIs in the treatment of the initial diagnosis of acute lymphoblastic leukemia (ALL), excluding relapse and transplantation, were investigated retrospectively. The patients were 152 first-diagnosed ALL cases (85 males and 67 females) admitted to our hospital between April 2007 and December 2024. The median age of these patients was 6.8 years. The median leukocyte count was 10.2×10 9 /L and the cell surface markers of the blasts were B precursor in 124 cases, T in 20 cases, mature B in 3 cases, and mixed lineage in 5 cases. The diagnosis of IFI was based on EORTC/MSG diagnostic criteria. Sixteen of the 152 patients (10.5%) were found to have IFIs; one was "proven," 7 were "probable," and 8 were "possible." The median time of IFI onset from the start of ALL treatment was 41 days (-7 to 258  d), with 56.3% of cases occurring at first onset of ALL or during induction therapy. Although 4 of 16 patients with IFIs died, IFI was the direct cause of death in 2 cases. Age 7.5 years or older was the only risk factor for IFI.

Idiopathic pneumonia syndrome (IPS) is a serious complication following allogeneic hematopoietic cell transplantation (HCT), often treated with methylprednisolone (mPSL) pulse therapy. However, treatment responses vary. This study aimed to identify predictors of poor response to mPSL monotherapy. Among 289 patients who underwent allogeneic HCT, 25 developed IPS and received mPSL pulse therapy. Clinical responses were categorized as complete (CCR), partial (PCR), or no response (NR), based on oxygen requirements within 28 days. We compared baseline characteristics of responders (CCR: n = 5; PCR: n = 6) and non-responders (NR: n = 14). Univariate analysis revealed that IPS onset on day +73 or later (p = 0.033), reduced intensity conditioning (p = 0.033), use of total body irradiation (p = 0.049) or fludarabine (p = 0.042), and nonuse of busulfan (p = 0.049) in preparative regimens were associated with poor response. Multivariate analysis identified a longer time from transplantation to IPS onset as a significant predictor of poor response (Odds Ratio 1.017 per 1-day increase; 95% CI 1.007-1.036; p = 0.045). The present study may provide valuable insights into how the responsiveness to mPSL varies depending on the time of IPS onset. Alternative therapeutic strategies may be needed for patients with late-onset IPS.

Although the treatment of pediatric hematological neoplastic diseases has improved greatly, the incidence of febrile neutropenia (FN) is more frequent and sometimes proves fatal as chemotherapy is intensified. A prospective, randomized study was performed to compare the usefulness of 2-hour drip infusions of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) for pediatric patients with FN. Ninety-three patients with 405 febrile episodes were randomly assigned to receive MEPM or PIPC/TAZ. MEPM 120 mg/kg/day was administered as a 2-hour drip infusion three times a day, whereas PIPC/TAZ 360 mg/kg/day was administered as a 2-hour drip infusion four times a day. In addition, in cases that failed first-line therapy, the antibiotic administration was alternated and randomized with or without intravenous immunoglobulin (IVIG) as the second-line treatment. As the first-line treatment, MEPM was effective in 74.8% of the 206 episodes, and PIPC/TAZ was effective in 74.9% of the 199 episodes. The total success rate in second-line treatment was 65.6%. MEPM was effective in 70.8% of the 48 episodes, and PIPC/TAZ was effective in 60.4% of the 48 episodes. The combined first- and second-line treatment efficacy rates were 89.4% for the first-line treatment with MEPM and the second-line treatment with PIPC/TAZ group and 91.3% in the first-line treatment with PIPC/TAZ and second-line treatment with MEPM groups, with an overall efficacy rate of 90.4%, an excellent result. However, the efficacy of IVIG could not be proven in this study. Adolescents and young adults in the present study also presented with lower rates of antibiotic efficacy.

Hepatic cirrhosis is a very rare complication of hematopoietic stem cell transplantation (SCT) and of neuroblastoma. We encountered two patients developing cirrhosis after SCT against neuroblastoma. A 6-year-old boy who had received allogeneic bone marrow transplantation developed cirrhosis 10 years after the SCT with the massive upper gastrointestinal hemorrhage. A 27-year-old man receiving allogeneic cord blood transplantation against recurrence of neuroblastoma, died of liver failure due to histological cirrhosis 1 year after the SCT. We could not detect the definite etiologic candidates of cirrhosis; however, careful monitoring appears warranted to avoid overlooking the onset and progression of cirrhosis after SCT.

Abstract Background The management of chemotherapy-induced nausea and vomiting (CINV) is of primary concern for both patients with cancer and medical workers. Refractory or breakthrough CINV is especially difficult to deal with and necessitates a different approach. Vitamin B1 deficiency is likely to occur during cancer chemotherapy, with early symptoms of fatigue, anorexia, nausea and vomiting. The efficacy of vitamin B1 for the treatment of delayed or refractory CINV should be confirmed. Methods Serum vitamin B1 level was prospectively measured in patients experiencing persistent nausea and vomiting after chemotherapy. The response to vitamin B1 therapy was evaluated for three consecutive days after vitamin B1 infusion. Moreover, serum level of vitamin B1 at diagnosis of persistent delayed CINV was compared with the level before chemotherapy. Results In total, 408 courses of chemotherapy in 86 patients were analyzed. The median age at hospital admission of the enrolled patients was 10.7 years (0.2–25.2). Among these, 44 (10.8%) episodes of persistent delayed CINV were identified in 26 of the enrolled patients. At day 3, the overall response rate was 79.5%; 21 (47.7%) patients achieved a complete response and 14 (31.8%) patients achieved a partial response. The median vitamin B1 level at diagnosis of CINV was significantly lower than the value before chemotherapy (22.8, range 11.9–49.2 vs. 32.7, range 11.2 − 80.1, respectively, P < 0.001). Conclusion Patients with a malignant disease who experience persistent nausea and vomiting after chemotherapy often exhibit vitamin B1 deficiency. Vitamin B1 infusion may be beneficial for many of these patients.

Background: Control of bacterial and fungal infections is critical to improving outcomes in hematological neoplastic diseases of children and adolescents. In this study, a retrospective analysis of our previous studies on febrile neutropenia was performed to investigate bacteremia. Procedure: From August 2008 to December 2023, five antibiotic studies were performed for febrile and neutropenic pediatric patients who had been treated with chemotherapy, immunosuppressive therapy, or had received stem cell transplantation in the pediatric unit at Sapporo Hokuyu Hospital. The rate of positive blood culture, detected bacteria, and susceptibility of several types of antibiotics in febrile episodes were investigated. Results: Blood culture was positive in 133 of 1604 febrile episodes of 329 patients. Detected bacteria were Grampositive cocci (61.2 %), Gram-negative bacilli (27.6 %), Gram-negative cocci (0.7 %), and Gram-positive bacilli (10.4 %). The incidence of bacteremia over time showed a decreasing trend with each passing year. In particular, the incidence of bacteremia was around 10 % in 2008-2013, whereas it was often below 5 % after 2020; this decrease was statistically significant. Although almost all detected bacteria and their susceptibilities to antibiotics (piperacillin/tazobactam, meropenem, ceftazidime, and cefozopran) did not change over time, all Escherichia coli detected after 2014 were extended-spectrum beta-lactamase-producing bacteria.

We present the first demonstration of vortex surface reliefs with 2-, 4- and 6-spiral arms in azopolymers, herein termed a ‘galaxy-shaped surface relief’ by employing petal-like modes, formed of the positive and negative Laguerre-Gaussian modes.

BACKGROUND:A prospective evaluation of non-alcoholic fatty liver disease (NAFLD) during induction therapy for acute lymphoblastic leukemia (ALL) has not been performed. Herein, we prospectively investigated the frequency, risk factors, and outcomes of NAFLD during induction therapy in children and adolescents with B-cell precursor ALL (BCP-ALL). METHODS:This study enrolled 74 newly diagnosed BCP-ALL cases aged 1 year and older who were admitted to our department between January 2011 and December 2020. Median age was 6.6 years (1.3-17.5 years). Plain computed tomography (CT) of the upper abdomen was performed before induction therapy, and on days 15 and 29 after initiation of induction therapy. Patients with a liver/spleen CT ratio <0.9 were defined as having NAFLD. RESULTS:The frequency of NAFLD was 73%. Patients with NAFLD had a higher rate of hypertriglyceridemia. There was no significant difference in 5-year overall survival and event-free survival (EFS) between patients with and without NAFLD. However, after restricting the target age to 10 years and older, 5-year EFS was significantly higher in patients with NAFLD than in those without (88.5 vs. 42.9%, respectively, P = 0.037). Similarly, 5-year cumulative incidence of relapse (CIR) was significantly lower in patients with NAFLD than in those without it (5-year CIR, 6.3 vs. 57.1%, respectively, P = 0.013). CONCLUSION:Patients with NAFLD exhibit better outcomes including 5-year EFS and CIR. Further studies are necessary.

Nephroblastomatosis (NBM) is a precursor of Wilms tumor.We herein report a case in which Wilms tumor was initially suspected and the affected kidney was removed.The tumor was subsequently diagnosed as intralobar NBM and a favorable outcome was achieved with postoperative chemotherapy.A 2-year-old boy who presented with gross hematuria was found to have an enlarged left kidney with hydronephrosis.Needle biopsy of the left kidney suggested Wilms tumor and left nephrectomy was performed.The tumor was histopathologically diagnosed as intralobar NBM.Although NBM is regarded as a precancerous lesion, a definite treatment plan has not yet been established.In the present case, we used a similar chemotherapy regimen to that for Wilms tumor.Eight years after the completion of chemotherapy, Wilms tumor has not developed or recurred.Appropriate management plans need to be developed by accumulating similar cases.

BACKGROUND Lymphocyte reconstitution after hematopoietic stem cell transplantation (HSCT) is important for the prevention of infections, as well as for the reduction of recurrence, by its graft versus tumor effect. However, these lymphocytes may also play a role in the development of graft-versus-host disease (GVHD). Few studies have investigated the association between lymphocyte reconstitution and clinical outcomes after HSCT. METHODS This issue was investigated by retrospectively analyzing pediatric patients who received their first allogeneic-HSCT using a newly developed parameter, the LD-index, which evaluates both the intensity and duration of lymphopenia. A total of 101 patients underwent allo-HSCT from April 2007 to August 2019 in our hospital. Excluding patients who died before lymphocyte recovery or underwent multiple HSCT, 78 patients were analyzed for associations between the LD-index with various factors relating to HSCT. RESULTS A significantly high association was observed between a low LD-index and the incidence of chronic GVHD (P = 0.0019). Analysis of predictive factors for chronic GVHD was carried out using univariate analysis. Lower LD-index, donor source and duration of lymphopenia were found to be significant factors associated with chronic GVHD. Multivariate analysis, however, only identified an association between a lower LD-index and an increased incidence of chronic GVHD (P = 0.00081). CONCLUSIONS Early reconstitution of lymphocytes after allo-HSCT is associated with a higher incidence of chronic GVHD.

BACKGROUND:Childhood cancer survivors are at an increased risk of impaired renal function. The aim of the present study was to assess the frequency of and risk factors for long-term renal dysfunction in patients with solid tumors using the estimated glomerular filtration rate (eGFR).METHODS:We retrospectively evaluated eGFR in 52 patients with solid tumors (25 females, 27 males) who received chemotherapy and were regularly followed up in our institute. Decreased eGFR was defined as <90 ml/min/1.73 m2 . Cases under treatment and of death were excluded.RESULTS:Median age at the diagnosis of the primary disease was 2.4 years (range, 0.0-23.9 years) and the median follow-up period was 98.4 months (range, 14.4-231.6 months). The mean cumulative incidence of decreased eGFR was 24.7 ± 2.2%. Multivariate analysis showed that decreased eGFR correlated with an older age at diagnosis (≥2.3 years) (hazard ratio 7.330, p = 0.018).CONCLUSION:Although previous studies have indicated that the risk of long-term nephrotoxicity is higher in patients treated at a younger age, the present study showed that patients treated at an older age were at an increased risk of decreased eGFR.

Pediatrics InternationalVolume 64, Issue 1 e15267 Clinical Notes Hepatic cirrhosis after hematopoietic stem cell transplantation for neuroblastoma Daiki Hori, Corresponding Author Daiki Hori pippen33_dh@yahoo.co.jp orcid.org/0000-0003-0634-6961 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanCorrespondence: Daiki Hori, MD, Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan. Email: pippen33_dh@yahoo.co.jpSearch for more papers by this authorRyoji Kobayashi, Ryoji Kobayashi orcid.org/0000-0002-3937-0856 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorHirozumi Sano, Hirozumi Sano orcid.org/0000-0003-4183-4602 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorDaisuke Suzuki, Daisuke Suzuki Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorKunihiko Kobayashi, Kunihiko Kobayashi Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this author Daiki Hori, Corresponding Author Daiki Hori pippen33_dh@yahoo.co.jp orcid.org/0000-0003-0634-6961 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanCorrespondence: Daiki Hori, MD, Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Higashi-Sapporo 6-6, Shiroishi-ku, Sapporo 003-0006, Japan. Email: pippen33_dh@yahoo.co.jpSearch for more papers by this authorRyoji Kobayashi, Ryoji Kobayashi orcid.org/0000-0002-3937-0856 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorHirozumi Sano, Hirozumi Sano orcid.org/0000-0003-4183-4602 Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorDaisuke Suzuki, Daisuke Suzuki Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this authorKunihiko Kobayashi, Kunihiko Kobayashi Department of Hematology/Oncology for Children and Adolescents, Sapporo Hokuyu Hospital, Sapporo, JapanSearch for more papers by this author First published: 18 October 2022 https://doi.org/10.1111/ped.15267Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Supporting Information Filename Description ped15267-sup-0001-FigureS1.tiffTIFF image, 25.8 MB Fig. S1 CT of Case 1 on admission shows a tumor with huge cysts and partial calcification between the right lobe of the liver and the right kidney. ped15267-sup-0002-FigureS2.tiffTIFF image, 25.8 MB Fig. S2 CT and scintigraphy of Case 2 at the first presentation. (a, b) CT shows right adrenal neuroblastoma with calcifications (circle). (c) MIBG scintigraphy shows uptake in the right adrenal mass and bones. (d) Bone scintigraphy shows uptake in bones throughout the body, including the skull. ped15267-sup-0003-TableS1.docxWord 2007 document , 16.8 KB Table S1 Cumulative doses of chemotherapy. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume64, Issue1January/December 2022e15267 RelatedInformation

Administration of mesenchymal stromal cells (MSCs) represents a promising therapy for steroid-resistant acute graft-versus-host disease (aGVHD). However, its efficacy in pediatric patients with steroid-dependent aGVHD remains unclear, given the paucity of studies performed in children. In addition, the duration between the onset of aGVHD and MSC therapy is reportedly critical; a delay in MSC administration negatively impacts overall survival and response rate. Herein, we describe a case of a 14-year-old girl with steroid-dependent aGVHD who was successfully treated with MSCs following a prolonged duration from aGVHD diagnosis. The patient was diagnosed with T-cell lymphoblastic leukemia with central nervous system involvement and underwent cord blood transplantation (CBT). She developed severe gastrointestinal aGVHD on day +14 after CBT and was treated with a steroid; however, her aGVHD was repeatedly exacerbated upon tapering the steroid, later complicated by diabetic ketoacidosis. We eventually implemented MSC therapy for steroid-dependent aGVHD on day +109 after CBT. She rapidly responded to therapy, and her aGVHD was ameliorated even with steroid tapering. This case exemplifies the potential role of MSCs in treating pediatric patients with steroid-dependent aGVHD or late aGVHD.

The widespread recognition of the concept of sarcopenia, or muscle loss, has impacted the prognosis of patients undergoing high-intensity treatments. We focused on the effect of muscle loss on the prognosis of pediatric patients with hematologic diseases. A total of 65 patients with hematologic malignancies who underwent allogeneic HCT once were investigated. The change in cross-sectional psoas muscle area (PMA) measured on computed tomography (CT) images was expressed as the muscle loss index (MLI), which was calculated by dividing the pre-HCT PMA by the baseline PMA. In this study, patients with MLI values less than 0.85 were classified into the muscle loss group. Muscle loss was observed in 27 patients (41.5%). Patients who experienced muscle loss were older than those who did not. Muscle loss was an independent predictor of higher non-relapse mortality (NRM) (p = 0.012) and inferior overall survival (OS) (p = 0.045) at 5 years. Multivariate analysis showed that muscle loss was an independent risk factor for higher NRM (p = 0.046), and inferior EFS (p = 0.048). Muscle loss observed pre-HCT may be a predictor of increased NRM, poor OS and EFS in pediatric patients with hematologic malignancies undergoing allogeneic HCT.

Background The risk factors for invasive fungal infection have gradually become evident for pediatric patients with hematological diseases. Here we analyze the efficacy of liposomal amphotericin (L-AMB) for pediatric patients with febrile neutropenia using prophylactic voriconazole (VRCZ). Method We administered L-AMB (2.5 mg/kg/day) in patients with febrile neutropenia who were receiving prophylactic VRCZ (10 mg/kg/day, orally) and were resistant to second-line antibiotics therapy. Thirteen patients (5 males, 8 females) with 19 febrile neutropenia episodes were targeted in this analysis. The median age of the patients was 14 years (range, 1-19 years). Eighteen out of 19 episodes occurred in patients with acute myeloid leukemia, with the remaining episode occurring in a patient with acute unclassified leukemia. Results The median period from start of L-AMB administration to resolution of fever was 4 days (1-27 days). In 15 out of 19 episodes, fever resolved within 5 days from commencement of L-AMB administration. Using criteria proposed by T. J. Walsh et al., the success rate of L-AMB for febrile neutropenia was 89.5% in this study. Conclusions Although the sample size of our study was small, the extremely high efficacy of L-AMB warrants its administration in patients with febrile neutropenia who are receiving VRCZ.

High-dose methotrexate (HD-MTX) therapy is widely used in patients with acute lymphoblastic leukemia (ALL) and lymphoma. However, some patients experience delayed MTX elimination, which requires treatment suspension or dose reduction to avoid organ damage. This single-center retrospective analysis reviewed the clinical data of 88 children with ALL or non-Hodgkin lymphoma who received a total of 269 courses of HD-MTX therapy between April 2008 and April 2019. HD-MTX was defined as MTX administration at 2.0, 3.0, or 5.0 g/m2 over a 24-h period, and delayed MTX elimination was defined as a serum MTX concentration ≥ 1.0 µmol/L at 48 h after the start of HD-MTX. Clinical factors were compared between courses with and without delayed MTX elimination. MTX elimination was delayed in 21 of the 269 courses (7.8%). Multivariate analysis showed that first HD-MTX course (OR 4.04), lower urine volume per BSA on the first day of HD-MTX administration (< 2,675 mL/m2, OR 5.10), higher total bilirubin (> 0.5 mg/dL, OR 5.11), lower eGFR (< 136 mL/min/1.73 m2, OR 3.90), higher dose of MTX(> 3.0 g/m2, OR 10.8), and lower urine volume per BSA on the next day of starting HD-MTX (< 2,107 mL/m2, OR 3.43) were independent risk factors for delayed MTX elimination.

Background The impact of paranasal sinusitis on the clinical outcome of patients with cancer remains unknown. The aim of this study was to determine whether paranasal sinusitis at the initiation of chemotherapy (SAI) affects the development of infectious complications in children and adolescents with cancer. Methods A retrospective cohort analysis of patients aged 0-20 years with cancer who received chemotherapy was performed. SAI was defined as the presence of a fluid level or mucosal swelling or total opacity on sinus computed tomography examination before the initiation of chemotherapy. The primary outcome measures were the incidence of bacteremia, septic shock, and invasive fungal disease (IFD, including proven, probable, and possible cases). Results SAI was observed in 57 (44%) of 130 enrolled patients. There were no significant differences in age, sex, and disease distribution between the patients with SAI (SAI group) and those without (non-SAI group). There was no significant difference in the 1-year cumulative incidence of bacteremia or septic shock after treatment initiation between the two groups (bacteremia, SAI group 33% vs. non-SAI group 35%, P = 0.53; septic shock, SAI group 4% vs. non-SAI group 4%, P = 0.87). The 1-year cumulative incidence of IFD was higher in the SAI group than in the non-SAI group (22% vs. 6%, P = 0.012). Cumulative incidence analysis after inverse probability of treatment weighting adjustment showed that the SAI group was more likely to develop IFD (HR: 3.5, 95% CI: 1.1-11.2, P = 0.033). Conclusions Our findings suggest that patients with SAI may be at higher risk for IFD during chemotherapy.