BACKGROUND:Vitamin B12 deficiency is a significant health problem in infancy, particularly in developing countries. Oral treatment has emerged as an alternative to intramuscular therapy, but optimal dosing in infants remains unclear. METHODS:This retrospective study included 93 infants aged 1 to 12 months diagnosed with nutritional vitamin B12 deficiency. Patients received either 500 or 1000 µg oral cyanocobalamin. Laboratory parameters were evaluated at baseline, 2 months, and 4 months. RESULTS:Both treatment groups demonstrated significant increases in serum vitamin B12 levels and decreases in homocysteine levels (P<0.001). No significant difference was observed between the 500 and 1000 µg groups regarding hematological or biochemical response. Treatment was well tolerated with no reported adverse effects. CONCLUSIONS:Oral cyanocobalamin was associated with biochemical improvement and was well tolerated in infants under 1 year of age. Although no significant difference was observed between the 500 and 1000 µg regimens in this retrospective cohort, prospective noninferiority studies are needed to determine whether the lower dose is comparable with the higher dose.
Background: Loss of SDHB by immunohistochemistry (IHC) is a practical screening marker for SDH-deficient GIST. Observation: A 14-year-old boy had a gastric GIST (KIT/DOG1 positive). Next-generation sequencing identified a truncating SDHA variant (c.1401T>A, p.Cys467Ter). Notably, SDHB IHC was strongly positive despite molecular evidence of SDH deficiency. Conclusions: Retained SDHB staining does not exclude SDH-deficient GIST. When clinicopathologic features suggest SDH deficiency, comprehensive molecular testing—including germline assessment—should be pursued, even in the context of SDHB positivity, to avoid false reassurance and to inform counseling and surveillance.
BACKGROUND:Cytomegalovirus (CMV) infection is an underrecognized complication in children with acute lymphoblastic leukemia (ALL). While CMV disease is well documented in transplant recipients, its clinical course in nontransplant settings remains poorly defined. Disseminated ganciclovir-resistant CMV infection is a rare complication in nontransplant children with ALL, and its optimal management remains uncertain. OBSERVATIONS:We describe an 8-year-old patient with T-ALL receiving maintenance chemotherapy who developed high levels of CMV viremia without initial end-organ disease and subsequent emergence of ganciclovir-resistant CMV infection. Despite prolonged valganciclovir therapy and the subsequent use of foscarnet and maribavir, the patient developed CMV-related complications, including CMV retinitis. CONCLUSION:This case underscores the potential severity of CMV in nontransplant pediatric ALL with prolonged lymphopenia, challenges of antiviral resistance, and limited treatment options for central nervous system involvement. The progression from asymptomatic viremia to clinically significant CMV disease remains poorly understood. Enhanced CMV surveillance protocols and resistance-guided treatment strategies may be warranted in selected high-risk populations.
BACKGROUND:Laparoscopic nephrectomy for Wilms tumor remains controversial despite growing evidence supporting its feasibility. This study analyzed surgical and oncological outcomes according to the SIOP criteria and evaluated the hilar-to-central vessel distance as a potential selection parameter. METHODS:Retrospective analysis of 50 children with unilateral Wilms tumor treated between 2014 and 2020. Patients underwent open (ON=38) or laparoscopic (LN=12) nephrectomy following SIOP protocols. Laparoscopic selection required: tumor confined to the kidney, not crossing vertebral border, no venous thrombus, volume ≤300 mL, and adequate chemotherapy response. CT/MRI measurements included tumor volume and the distance between the hilar vessels and the aorta/vena cava. Outcomes included operative time, complications (Clavien-Dindo classification), conversion rate, lymph node yield, recurrence, and survival. RESULTS:Groups differed significantly in staging (stage I: LN 83.3% vs. ON 26.3%, P=0.003). Mean tumor volume after chemotherapy was lower in the LN group (87.81 vs. 394.72 cm3, P<0.001). Hilar-to-central vessel distance after chemotherapy was greater in the LN group (10.83 vs. 5.42 mm, P=0.005). Conversion rate was 16.7% (2/12) due to bleeding. No intraoperative tumor spillage occurred in the LN group, compared with 3 in the ON group. Postoperative complications occurred only in the ON group (4/38, 10.5%). Average LOS was 2.42 days (LN) versus 4.53 days (ON). Five-year event-free survival was 91.7% (LN) and 84.2% (ON). CONCLUSION:Laparoscopic nephrectomy for carefully selected Wilms tumor patients treated according to SIOP protocols demonstrated favorable perioperative outcomes consistent with appropriate patient selection. The hilar-to-central vessel distance showed statistical association with surgical approach at the group level, but did not discriminate conversion risk at the individual level. Integration of this metric should be studied as a potential adjunct to comprehensive assessment by experienced surgical teams, with prospective multicenter validation required before clinical implementation.
Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm typically defined by BCR::ABL1 p210 fusions isoforms. Observations: An 8-year-old female CML patient harbored a typical t(9;22)(q34;11) Philadelphia chromosome and BCR::ABL1 fusion by conventional karyotyping and FISH but lacked BCR::ABL1 p210 fusion transcripts by RT-PCR. Targeted next-generation sequencing (NGS) revealed BCR :: SPECC1L :: ABL1 fusion transcripts predicted to encode an in-frame BCR-exon-8::SPECC1L-exon-4::ABL1-exon-2 fusion protein retaining the tyrosine kinase domain. FISH and NGS were used for therapeutic imatinib monitoring given this atypical isoform. Conclusions: This case highlights the role of multimodal molecular diagnostics to diagnose and monitor pediatric CML patients with atypical fusion isoforms.
BACKGROUND:Central nervous system (CNS) immune reconstitution inflammatory syndrome (IRIS) is well characterized in HIV but exceedingly rare in pediatric hematologic malignancies. OBSERVATION:An 11.5-year-old girl with acute myeloid leukemia (AML) and probable invasive pulmonary mold infection developed an expansive right parieto-occipital lesion with a 14 mm midline shift during neutrophil recovery. Evaluation excluded leukemic infiltration and active infection. Probable CNS IRIS was diagnosed; dexamethasone with continued antifungal therapy produced rapid clinical and radiologic recovery, with sustained AML remission at 29 months. CONCLUSIONS:CNS IRIS should be considered in pediatric AML with unexplained neurological deterioration during neutrophil recovery; timely corticosteroid therapy can be life-saving.
BACKGROUND:Sirolimus is a first-line treatment for venous malformations in pediatric patients. Current studies describing adverse events have not shown an increased incidence of venous thromboembolism (VTE). OBSERVATION:We present a pediatric patient with a vascular anomaly who developed bilateral pulmonary emboli while on sirolimus with minimal other risk factors for clot development. CONCLUSIONS:While it is not possible to conclusively prove that the development of pulmonary emboli was related to sirolimus, given the possible association, clinicians who treat patients with vascular anomalies may need to consider patients treated with sirolimus at a higher risk for VTE.
Background: Primary renal Ewing sarcoma (EWS) is a rare but aggressive pediatric malignancy with poor outcomes and limited knowledge of its behavior and biology. The use of molecular markers as prognostic factors and local control strategies with surgical resection and radiation is not well-described for renal EWS. Observation: We document a case of stage IV renal EWS with 4.5 years of durable remission. Conclusion: We hypothesize the favorable outcome may be associated with the lack of specific genomic signatures ( STAG2 , CDKN2A , and TP53 ) and the use of upfront surgical resection followed by radiation for local control.
Background and Aims: Methylene-tetrahydrofolate dehydrogenase 1 (MTHFD1) deficiency is a rare inborn error of immunity (IEI) involving defects in folate metabolism. It can present with combined immunodeficiency and variable phenotypic features, including recurrent bacterial infections, megaloblastic anemia, and failure to thrive. Methods: We describe 2 unrelated Kuwaiti children with MTHFD1 deficiency caused by a homozygous pathogenic variant [c.517C>T (Arg173Cys)]. Results: Both cases presented with unexplained megaloblastic anemia, recurrent sinopulmonary infections, failure to thrive, and developmental delay. The first patient, a 10-year-old girl, was diagnosed with combined immunodeficiency and autoimmune thyroiditis. Treatment with folic acid resulted in significant clinical improvement. The second patient, a 3-year-old girl, presented with sepsis secondary to progressive lobar pneumonia and bone marrow failure. Despite intensive treatment, including broad-spectrum antibiotics, antifungals, IVIG, and dexamethasone for suspected hemophagocytic lymphohistiocytosis, she developed severe complications and passed away on day 18 of PICU admission. Conclusion: As there is no specific clinical or laboratory phenotype for most IEIs, we emphasize the importance of molecular diagnosis through urgent genetic testing in patients with suspected MTHFD1 deficiency. Precision therapy with prompt folate or folinic acid supplementation can significantly improve outcomes, as evidenced by the survival of one patient with minimal intervention.
Racial and ethnic survival disparities exist in pediatric and young adult acute lymphoblastic leukemia (ALL), with differential treatment toxicity and setting of care as possible drivers. Whether treatment cost and utilization disparities exist, or how they may contribute to differences in ALL survival, is unknown. Patients with ALL diagnosed between 2000 and 2019 at ages 1 to 24 years were identified using ICD-9/10 codes in the administrative claims data from the OptumLabs Data Warehouse and the Surveillance, Epidemiology, and End Results program. Sex, race and ethnicity, age, year, and subtype of ALL diagnosis were collected. Reimbursed treatment cost and utilization (number of inpatient and outpatient days) were computed over the initial 8 months of treatment. Regression models assessed associations with demographic and clinical characteristics. Survival analyses assessed associations between race and ethnicity and overall survival. Among 374 individuals with ALL, treatment costs were 57% lower for Black patients than for White patients (estimate 0.43, 95% CI: 0.19-0.96; P =0.04). Utilization was similar across groups, though Black patients had 24% fewer outpatient visits (estimate 0.76, 95% CI: 0.58-0.99; P =0.04). No significant differences in survival were detected, but observations are consistent with previous reports. Despite a small sample size, the statistically significantly lower cost and utilization among Black relative to White ALL patients are concerning and warrant further research.
Neuroblastoma (NB) associated with opsoclonus-myoclonus ataxia syndrome (NB-OMAS) has a favorable cancer prognosis but complicated long-term neurological sequelae. The aim was to evaluate the clinical profile and outcomes of NB-OMAS in children at a single tertiary care center in India. Children aged younger than 14 years with NB-OMAS treated between January 1, 2013 and December 31, 2022, were retrospectively analyzed. Among 189 children with NB, 12 (6.3%) had OMAS. The mean age at diagnosis was 17.17±5.35 months. All patients were either stage L1 or L2; 7 (58.3%) had NB diagnosed before 18 months of age, and 9/12 (75%) had low-risk NB. Ataxia (83.3%) and opsoclonus (66.6%) were common symptoms with a mean symptom duration of 12.08±12.05 months. The mean OMAS score significantly improved from 6.17±2.87 (baseline) to 0.75±1.21 (treatment completion) (P=0.002). Immunosuppressive therapy (IST) was given for a mean duration of 15.14±6.59 months to 58.3% of patients. At a median follow-up of 16.5 months (range: 3 to 118 mo), 91.7% and 75% had complete remission of NB and OMAS, respectively. Higher OMAS scores at presentation predicted prolonged symptoms (P=0.001) and incomplete OMAS response (P=0.048). Four (33%) had developmental delay at the last follow-up. In an LMIC setting, NB-OMAS has excellent oncological outcomes, but long-term neurological challenges remain, especially for children with a high OMAS score.
This retrospective observational study examined the timing and sequence of clinical events during terminal hospitalization in pediatric oncology patients with progressive, treatment-refractory disease. The study included 54 children with solid tumors who died as inpatients at a tertiary center in Turkey between 2015 and 2025. Clinical events were mapped from admission to death, including both the time from admission to event onset and the interval from event onset to death. The most common diagnoses were neuroblastoma, Ewing sarcoma, and osteosarcoma. Patients experienced a mean of 3.1 ± 1.9 clinical events during terminal hospitalization. The most frequent events were intubation (64.8%), hypotension (57.4%), sepsis (48.1%), and electrolyte imbalance (35.2%). Temporal analysis showed that sepsis and hypotension occurred relatively early, with median onset times of 15.5 and 15 days after admission, respectively, whereas acute renal failure emerged later, with a median onset of 49 days. New-onset hypotension, intubation, and acute renal failure were closely associated with imminent death, with median intervals from event onset to death of 6, 7, and 3.5 days, respectively. These findings suggest that terminal decline in pediatric oncology follows measurable temporal patterns, and objective events such as hypotension, intubation, and acute renal failure may help clinicians recognize irreversible deterioration earlier.
Hepatobiliary complications are common in children with sickle cell anemia (SCA) due to chronic hemolysis and vaso-occlusion, but are often underdiagnosed in low-resource settings where imaging is limited. This hospital-based cross-sectional study, conducted from March to May 2023, assessed the prevalence and characteristics of hepatobiliary abnormalities using ultrasound among children younger than 18 years with SCA at a tertiary hospital in Tanzania. Demographic and clinical characteristics, laboratory findings, and abdominal ultrasonography were obtained. Logistic regression was used to identify factors associated with hepatobiliary abnormalities. A total of 194 children aged 2 to 16 years were enrolled, of whom 52% were male and 47.9% were receiving hydroxyurea. The overall prevalence of hepatobiliary abnormalities was 57.2%. The most common findings were hepatomegaly (41%), low portal vein peak systolic velocity (14%), and biliary calculi or sludge (9%). Children aged 6 to 10 years (aOR=0.1, 95% CI: 0.05-0.3; P <0.001) and 11 to 16 years (aOR=0.1, 95% CI: 0.03-0.2; P <0.001) had lower odds of abnormalities compared with those aged 2 to 5 years, while biliary calculi or sludge were more frequent in older children ( P =0.005). Hepatobiliary abnormalities are highly prevalent and often asymptomatic, highlighting the importance of early screening and routine monitoring.
BACKGROUND:Pneumocystis jirovecii pneumonia (PJP) is a rapidly progressive and potentially fatal opportunistic infection in non-HIV immunocompromised children. Mortality is particularly high when PJP progresses to acute respiratory distress syndrome (ARDS). The role of extracorporeal membrane oxygenation (ECMO) in this setting remains limited to select reports. CASE PRESENTATION:We report a 3-year-old boy with multisystem Langerhans cell histiocytosis receiving vinblastine and corticosteroids who developed severe PJP during consolidation therapy. Despite early initiation of high-dose trimethoprim-sulfamethoxazole, adjunctive corticosteroids, and escalation to invasive mechanical ventilation, he developed refractory hypoxemic and hypercapnic respiratory failure. Bronchoalveolar lavage multiplex polymerase chain reaction confirmed Pneumocystis jirovecii with concurrent Klebsiella pneumoniae. In the absence of hemodynamic compromise or multiorgan dysfunction, venovenous (V-V) ECMO was initiated as rescue support. Rapid improvement in gas exchange allowed decannulation on day 6 and extubation by day 8. Radiologic resolution occurred within 2 weeks. The child completed antimicrobial therapy, resumed maintenance chemotherapy, and remains well at 10-month follow-up on secondary PJP prophylaxis. CONCLUSION:This case underscores the importance of early recognition and aggressive supportive care. In selected patients with isolated, potentially reversible respiratory failure, timely initiation of V-V ECMO can be lifesaving and may facilitate recovery while definitive antimicrobial therapy takes effect.
INTRODUCTION:Allogenic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment modality in patients with transfusion-dependent thalassemia (TDT). Over the past decade, there has been a shift towards reduced-toxicity conditioning regimens such as Treosulfan-Thiotepa-Fludarabine (TTF) due to its favorable toxicity profile, potent immunosuppression, and myeloablative effects. This study explores the outcomes of TTF-based conditioning in pediatric TDT patients undergoing allogenic HSCT. METHODS:This is a single-center retrospective analysis of 74 pediatric patients who underwent allogenic HSCT using the TTF conditioning regimen at our center from January 2017 to May 2025. RESULTS:The median age at transplant was 6.2 years (range: 1 to 18 y) and Male: female was 1.8:1. Donor types included matched sibling donor (MSD) in 45 patients (60.8%), matched unrelated donor (MUD) in 16 (21.6%), haploidentical donor in 9 (12.2%) and matched related donor (MRD) in 4 patients (5.4%). Pesaro classes I, II, and III were seen in 24 (32.4%), 32 (43.2%), and 18 (24.3%) patients, respectively. Peripheral blood was the stem cell source in all patients. Median stem cell dose was 5.2 million/kg (range: 4.2 to 6.5 million/kg). Four patients (5.4%) had primary graft failure. In the remaining patients, neutrophil and platelet engraftment occurred at a median of 14 days (range: 11 to 25 d) and 18 days (range: 13 to 36 d), respectively. Mixed chimerism was observed in 10 (13.5%) patients, of whom 2 developed secondary graft failure with autologous recovery. Acute and chronic graft-versus-host disease occurred in 25 (33.7%) and 7 (9.4%) patients, respectively. Cytomegalovirus reactivation was seen in 42 patients (56.7%). Six children (8.1%) suffered from veno-occlusive disease. At a median follow-up of 45.2 months (range: 1.5 to 102 mo), 5-year overall and thalassemia-free survival were 82.2% and 77.7%, respectively. Subgroup analysis by Pesaro classification showed 5-year OS rates of 83.9% for class 1+2 and 78.6% for class 3 (P=0.28). Five-year TFS was 82% for class 1+2 and 65.5% for class 3 (P=0.049). When comparing matched sibling and matched related donor transplants with alternate donor transplants (haploidentical and matched unrelated), the 5-year OS and TFS were significantly higher in the matched donor group (95% vs. 57.3%, P=0.001, and 88.3% vs. 57.3%, P=0.024). CONCLUSION:TTF conditioning with a peripheral blood stem cell graft is a well-tolerated and effective approach for allogeneic HSCT in thalassemia. It demonstrates reduced toxicity and favorable transplant outcomes, with superior results in the matched family donor setting compared with the alternate donor group, supporting its role as a promising alternative to traditional busulfan-based conditioning regimens.
BACKGROUND:Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is useful for staging rhabdomyosarcoma. Using this modality as a predictor of outcome and for disease surveillance in rhabdomyosarcoma is conflicting. OBSERVATIONS:Case report of an adolescent being treated for metastatic fusion-positive rhabdomyosarcoma who had a new 18F-FDG-PET avid focus in the radiation field of the primary site with increasing standard uptake value during systemic chemotherapy and primary tumor local therapy that was worrisome for disease progression. CONCLUSIONS:This lesion was resected and confirmed as terminally cytodifferentiated (mature) rhabdomyoblasts on histopathology. He remains in remission 26 months following resection and 20 months following treatment.
Nonaccidental trauma (NAT) can present with bleeding symptoms. Judicious use of hematologic testing is recommended to evaluate for medical causes of bleeding, while acknowledging inherited bleeding disorders and NAT may be present concurrently. A retrospective chart review using the Pediatric Health Information System database identified pediatric patients <18 years of age with an ICD diagnostic code for NAT associated with admission. Using laboratory charge data, we identified the hematologic testing sent and the number of encounters with expanded hematologic testing (EHT), defined as testing beyond CBC, PT, PTT, Factor IX, and von Willebrand testing (and fibrinogen/d-dimer in cases of intracranial hemorrhage). In 9561 admissions meeting inclusion criteria, laboratory testing was sent in 91.9% of encounters and EHT in 35.9% of encounters. The most common EHT test being fibrinogen. EHT was associated with a significant increase in laboratory-associated charges. Only 69 children (0.7%) were later identified to have an underlying bleeding disorder, most commonly von Willebrand Disease. Factors associated with EHT included hematology consultation, young age, higher income, and private health insurance. Despite few patients diagnosed with underlying bleeding disorders, EHT was frequently obtained. Sociodemographic features may influence testing decisions. Adherence to guidelines for evaluation may help reduce disparities.
BACKGROUND:Chemotherapy for pediatric leukemia induces profound immunosuppression, resulting in waning protection against vaccine-preventable diseases. Despite high survival rates, standardized revaccination protocols for non-transplant survivors remain controversial. We aimed to assess the serologic immunity to measles, mumps, rubella, and varicella among pediatric leukemia survivors and to identify clinical and treatment-related determinants of immune persistence. METHODS:In this retrospective cohort study, 192 pediatric leukemia survivors treated with non-HSCT chemotherapy at Phoenix Children's Hospital (2021 to 2023) underwent serologic testing for measles, mumps, rubella, and varicella IgG antibodies. Demographic, clinical, and immunization data were retrieved from institutional and state registries. Associations between patient characteristics and serologic immunity were analyzed using logistic regression. RESULTS:At a mean of 6.51 years following chemotherapy completion, the overall seropositivity rates were 37.0% for measles, 40.6% for mumps, 70.8% for rubella, and 24.5% for varicella. Survivors who received post-chemotherapy vaccination demonstrated significantly higher seropositivity for rubella (81.9% vs. 64.1%, P =0.004) and varicella (35.6% vs. 16.3%, P =0.005), with higher but non-significant seropositivity for measles and mumps. Low-risk B-cell acute lymphoblastic leukemia (ALL) patients exhibited higher immunity compared with high-risk patients, with significant differences observed for mumps (53.6% vs. 24.6%, P =0.0009) and rubella (81.2% vs. 66.7%, P =0.039). Moreover, a shorter interval from therapy completion was associated with improved rubella immunity (adjusted OR=0.753; 95% CI: 0.66-0.86). Post-chemotherapy revaccination was independently associated with increased odds of rubella (adjusted OR=4.89; 95% CI: 1.762-13.572) and varicella (adjusted OR=2.65; 95% CI: 1.124-6.26) immunity. CONCLUSION:Substantial attenuation of vaccine-derived immunity persists years after chemotherapy completion in pediatric leukemia survivors. Both treatment intensity and absence of post-chemotherapy revaccination contribute to impaired long-term humoral immunity. These findings support routine revaccinations for all non-transplant pediatric leukemia survivors and underscore the need for risk-adapted, individualized survivorship immunization strategies.
BACKGROUND:Systemic mastocytosis (SM) with associated acute myeloid leukemia (AML) is a rare malignancy usually linked to KIT p.D816V mutations. OBSERVATIONS:We report a 17-year-old female with RUNX1::RUNX1T1 -positive AML and florid mast cell proliferation harboring a rare KIT exon 8 deletion (p.Asp419del). Diagnosis required integration of morphology, immunophenotyping, and polymerase chain reaction, as routine NGS failed to detect the mutation. Despite remission following intensive chemotherapy and imatinib, the patient developed persistent mastocytosis and succumbed to septic shock. CONCLUSIONS:This first reported case of SM-AML with KIT p.Asp419del highlights the need for comprehensive molecular testing and tailored therapy in atypical presentations.
