So-ichi Suenobu

Laparoscopic splenopexy for pediatric wandering spleen

Wandering spleen is an uncommon condition, showing a splenic hypermobility that results from laxity or maldevelopment of its suspensory ligament. This condition results in constant danger of splenic torsion and infarction. Wandering spleen was diagnosed in a 2-year-old girl who complained of intermittent abdominal pain, and viability of the spleen was confirmed by doppler ultrasound scan. Elective laparoscopic splenopexy was performed by anchoring the spleen wrapped in absorbable mesh. To our knowledge, this is the first reported case of laparoscopic splenopexy for wandering spleen. The authors believe that this approach is a safe and effective procedure for wandering spleen with the advantage of minimally invasive surgery.

IKZF1 deletion is associated with a poor outcome in pediatric B-cell precursor acute lymphoblastic leukemia in Japan

Genetic alterations of Ikaros family zinc finger protein 1 (IKZF1), point mutations in Janus kinase 2 (JAK2), and overexpression of cytokine receptor‐like factor 2 (CRLF2) were recently reported to be associated with poor outcomes in pediatric B‐cell precursor (BCP)‐ALL. Herein, we conducted genetic analyses of IKZF1 deletion, point mutation of JAK2 exon 16, 17, and 21, CRLF2 expression, the presence of P2RY8‐CRLF2 fusion and F232C mutation in CRLF2 in 202 pediatric BCP‐ALL patients newly diagnosed and registered in Japan Childhood Leukemia Study ALL02 protocol to find out if alterations in these genes are determinants of poor outcome. All patients showed good response to initial prednisolone (PSL) treatment. Ph+, infantile, and Down syndrome–associated ALL were excluded. Deletion of IKZF1 occurred in 19/202 patients (9.4%) and CRLF2 overexpression occurred in 16/107 (15.0%), which are similar to previous reports. Patients with IKZF1 deletion had reduced event‐free survival (EFS) and overall survival (OS) compared to those in patients without IKZF1 deletion (5‐year EFS, 62.7% vs. 88.8%, 5‐year OS, 71.8% vs. 90.2%). Our data also showed significantly inferior 5‐year EFS (48.6% vs. 84.7%, log rank P = 0.0003) and 5‐year OS (62.3% vs. 85.4%, log rank P = 0.009) in NCI‐HR patients (n = 97). JAK2 mutations and P2RY8‐CRLF2 fusion were rarely detected. IKZF1 deletion was identified as adverse prognostic factor even in pediatric BCP‐ALL in NCI‐HR showing good response to PSL.

Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group

The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR–ABL-negative ALL. Patients aged 15–24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58–75%) and 73% (95% CI 64–80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR–ABL-negative ALL.

A relapse of systemic type juvenile idiopathic arthritis after a rubella vaccination in a patient during a long-term remission period

An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis (JIA) had maintained in remission for the previous 4 years while taking only a small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart failure five days after receiving a live-attenuated rubella vaccine, which was a primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies increased, and her laboratory findings such as a leukocytosis, elevated serum levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the findings observed during her previous JIA active stage. After being administration of co-therapy with steroid pulse, ibuprofen, methotrexate and phosphodiesterase inhibitor gradually improved her clinical symptoms such as spiky fever, heart failure and arthralgia. Her intermittent fever and increased serum levels of CRP and IL-6, however, have been sustained for more than 2 years, and this prolonged active clinical course therefore differed from her previous JIA active stage.This abrupt relapse only five days after vaccination was suggested not to be directly related with rubella infection, but instead to be related with the molecular mimicry between rubella and JIA.

Theophylline-associated seizures and their clinical characterizations

Background: To elucidate the basic mechanism of theophylline‐associated seizures (TAS), the clinical symptoms, electroencephalogram (EEG) and neuroradiological imaging of eight pediatric patients were all retrospectively evaluated.

An overall characterization of pediatric acute lymphoblastic leukemia with CRLF2 overexpression

For an overall characterization of pediatric B‐cell precursor acute lymphoblastic leukemia (BCPALL) with CRLF2 overexpression (OE), we conducted genetic analysis of CRLF2 in 167 pediatric BCPALL patients. CRLF2 OE was detected in 30 (18%) of 167 patients, the P2RY8‐CRLF2 fusion was identified in only 3 (1.8%) of 167 patients, all of which demonstrated CRLF2 OE. Moreover, CRLF2 gain was identified in 18 (11%) of 167 patients. Messenger RNA sequencing revealed a novel fusion transcript, CSF2RA‐CRLF2, in a case with CRLF2 OE, suggesting that this fusion is associated with CRLF2 OE. In survival analysis, no significant differences in 5‐year event‐free survival (EFS) and overall survival were observed between patients with and without CRLF2 OE (70.7 vs. 75.4%, log rank P = 0.68 and 96.4 vs. 82.1%, log rank P = 0.11, respectively). However, a significant difference in 5‐year EFS between CRLF2 OE patients with and without IKZF1 deletion was observed (44.4 vs. 83.1%, log rank P = 0.02). In multivariate analysis, only IKZF1 deletion was a significant predictor of inferior OS (hazard ratio: 2.427, P = 0.04).These findings suggest that CRLF2 OE is not an independent prognostic factor in pediatric BCPALL.

The indication and effectiveness of low-dose erythromycin therapy in pediatric patients with bronchial asthma*

Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S‐i, Izumi T. The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma.
Pediatr Allergy Immunol 2010: 21: 489–492.
© 2010 John Wiley & Sons A/S

The subclassification of schizencephaly and its clinical characterization

We subclassified schizencephaly based on the association with optic nerve hypoplasia (ONH) and the absence of the septum pellucidum (ASP), and then characterized their clinical presentation and prognosis. The subjects of our study consisted of 10 cases with a mean age at the final evaluation of 10 years 3 months (range, 7 months to 25 years). The subclassification of schizencephaly consisted of the septo-optic dysplasia (SOD) group (n=3), with ONH and ASP; the optic hypoplasia (OHP) group (n=2), with ONH and without ASP, and; the classical group (n=5), without ONH. The subjects with an open-lip cleft in the SOD and the classical group showed hydrocephalus, but those in the OHP group did not. The SOD and the OHP group displayed severe psychomotor retardation regardless of the cleft morphology, but in the classical group, the subjects with an open-lip cleft or with diffuse cortical dysplasia were severely retarded. The SOD and the OHP group displayed intractable epilepsy. In contrast, all subjects in the classical group showed good control of epilepsy. The results of our investigation show that the subclassification of schizencephaly based on the association with ONH and ASP is useful. The SOD group means early fetal brain injury which results in extended cortical dysplasia while the OHP group means severe destructive brain injury which results in cerebro-cerebellar disruption.

Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG).

This study reviewed the clinical characteristics of 112 pediatric B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) patients with TCF3‐PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL02 protocol (n = 82) and Childrens Cancer and Leukemia Study Group (CCLSG) ALL 2004 protocol (n = 30). The 3‐year event‐free survival (EFS) and overall survival (OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5‐year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3‐PBX1 positive BCP‐ALL.

Detection of platelet-binding anti-measles and anti-rubella virus IgG antibodies in infants with vaccine-induced thrombocytopenic purpura.

A 15-month-old infant presented with thrombocytopenic purpura after sequential administration of measles-rubella combined vaccine, varicella vaccine and mumps vaccine every 4 weeks. Her thrombocytopenia persisted for more than 12 months. Both anti-measles and anti-rubella virus IgG antibodies were detected in the patients-isolated platelets on day 154 of illness, which were not detected when there was a reduction of the serum IgG antibody titers on days 298 and 373 of illness, respectively.We also detected the isolated platelet-binding anti-measles and anti-rubella virus IgG antibodies in two other pediatric patients. This is the first report demonstrating direct evidence of vaccine-induced thrombocytopenic purpura.