Journal of Pediatric Hematology/Oncology最新文献

Background: Above 50% of LCH cases show BRAF-mutations, which can be targeted by dabrafenib in refractory disease.

Observations: Here, we report on a patient with neonatal multisystem, BRAF-mutated LCH refractory to conventional treatment with vinblastine and prednisolone. Duodenal involvement rendered oral nutrition impossible, and the patient was severely ill with pancytopenia, hepatic dysfunction, cholestasis, and septic episodes. After initiation of targeted therapy with dabrafenib, the patient achieved sustained clinical remission.

Conclusions: Multisystem LCH is a rare and potentially life-threatening disease that can mimic various neonatal conditions. A high index of suspicion is necessary for diagnosis. Timely initiation of targeted therapy may prevent irreversible organ damage.

Atypical teratoid/rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) tumors. Typically, AT/RT is classified as SMARCB1 (INI-1) deficient or as SMARCA4 (BRG1) deficient. In this case, we describe a unique case of AT/RT with a novel SMARCA4 missense variant identified on next-generation sequencing but retained expression of INI-1 and BRG-1 on immunohistochemistry. Diagnosis of the tumor and discovery of the novel SMARCA4 variant was only possible after comprehensive tumor molecular testing tailored for pediatric malignancies. This case highlights the importance of molecular genetic testing as part of a workup in neoplasms concerning for possible AT/RT.

Mutations that alter the structure of red blood cells, including the mutations that cause sickle cell disease (SCD), are common globally because they protect against malaria. Patients with SCD rarely develop severe anemia that requires blood transfusions before 6 months of age. We present the case of a patient with SCD who developed severe anemia requiring a blood transfusion at 6 weeks old and subsequent transfusions throughout her first two and a half years of life. Next-generation sequencing genetic testing revealed that the patient also had hereditary pyropoikilocytosis (HPP), a severe form of hereditary elliptocytosis (HE), and was heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Following splenectomy, the frequency of her transfusions slightly decreased. This case demonstrates that HPP modifies the severity of SCD and highlights the importance of considering additional hematologic conditions and obtaining genetic testing in patients with SCD and early-onset anemia.

Background: Rare factor deficiency (RFD) is characterized by a deficiency of factor (F)I, FII, FV, FVII, FX, FXI, FXII, FXIII, or a combined deficiency of FV+FVIII or vitamin K-dependent factors. The prevalence of RFD ranges from 1/1,000,000 to 3,000,000. Combined deficiencies of vitamin K-related factors have been described in 30 families worldwide, and these patients can present with a wide range of clinical symptoms, from mucocutaneous bleeding to life-threatening symptoms such as central nervous system and gastrointestinal bleeding.

Objective: This study aimed to contribute to the literature on RFD.

Material and methods: This retrospective study analyzed data from 43 children with RFD.

Results: The most common factor deficiencies were FVII (n=13); whereas the other deficiencies were FI (n=1), FV (n=2), FV+FVIII (n=2), FX (n=6), FXI (n=5), FXII (n=9), FXIII (n=3), and vitamin K-dependent combined factor deficiency (n=2). Acute and severe bleeding was controlled by treatment in 6 patients, and 12 patients with recurrent bleeding symptoms received prophylaxis. RFDs were more common in regions with high rates of consanguineous marriage, and in our study, 16 (16/43) of the cases were found to have consanguineous marriages between parents.

Conclusions: It is important to improve genetic counseling and access to testing for family members with RFD due to autosomal recessive inheritance. Delays in diagnosis and treatment and lack of adequate prevention are important risk factors for life-threatening bleeding.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from maternal antibodies targeting fetal platelets during pregnancy, often causing hemorrhagic manifestations detectable antenatally or shortly after birth. We report an atypical form of FNAIT with delayed onset in a healthy, breastfed male infant who developed diffuse petechiae 2 weeks after birth due to severe thrombocytopenia. The mother was shown to be negative for the human platelet antigen-1a (HPA-1a) allele but had anti-HPA-1a IgG antibodies, while the father and newborn were HPA-1a positive, confirming the diagnosis. Despite intravenous immunoglobulins and platelet transfusions, the recovery was slow. Analysis of breast milk demonstrated the presence of anti-HPA-1a IgG antibodies. The unusual clinical presentation 2 weeks after birth and the slow platelet recovery under appropriate treatment suggest postnatal transfer of maternal anti-HPA-1a antibodies or B lymphocytes producing these antibodies to the newborn, which may possibly have occurred through breastfeeding. Further research is needed to validate these findings and understand the role of breast milk in provoking the disease. Early detection and management remain essential to prevent serious complications associated with FNAIT.

Eosinophilia is rare in pediatric acute lymphoblastic leukemia. In this report, we present a case of acute lymphoblastic leukemia with marked eosinophilia, whose diagnosis was delayed because of clonorchiasis.

This offering represents part 2b of a second set of 5 additional contributions of pediatric hematology/oncology to the diagnosis, treatment, and potential cure of precursor B-cell acute lymphoblastic leukemia. It contains numbers 16 to 20 and includes (16) allogeneic hematopoietic stem cell transplantation, newer immunotherapies including (17) blinatumomab, and (18) inotuzumab ozogamicin, (19) ploidy, and (20) creation of the "day hospital" to administer outpatient care to children with acute lymphoblastic leukemia and other cancers. These and the other reviewed contributions have had a significant role in improving the quality and duration of the lives of children, most of whom faced tragic and painful death back in the 1950s and 1960s. Most of our early optimistic goals were achieved and have benefitted substantially our patients, providing those of us who participated in many of these key clinical trials, a profound sense of accomplishment.

Acute leukemias of ambiguous lineage (ALAL) is a rare type of acute leukemia, referring to a group of disorders characterized by a combination of myeloid, lymphoid, or more lineages, whose incidence is significantly lower in children than adults. Here, we summarized the clinical features and outcomes of 36 pediatric ALAL patients in past 16 years. The patients diagnosed as ALAL based on the criteria of EGIL scoring system in 1998 (EGIL 1998) and/or the 2016 revisions to the WHO classification (WHO 2016) from January 1, 2005 to December 1, 2021 were included, respectively. During follow-up for a median 22 months, the median leukemia-free survival (LFS) was 18 months (0 to 172 mo) and the median overall survival (OS) was 22 months (1 to 173 mo), with a 5-year LFS rate of 67.3±9.2% and a 5-year OS rate of 66.0±10.7%. Patients who sustained negative minimal residual disease after 2 courses of standardized chemotherapy contributed to better 5-year OS (100% vs. 37.2±22.0%, P =0.028) and LFS (100% vs. 46.7±16.6%, P =0.028).