The treatment outcomes of relapsed or refractory neuroblastoma have been unsatisfactory till date. We reported two cases of adoptive immunotherapy using cytokine-induced killer (CIK) cells against relapsed or refractory neuroblastoma. CIK cell production was attempted in three patients, out of which two patients exhibited adequate levels of CIK cell production. Two patients completed full term of CIK cell infusions (weekly for 6 weeks and then biweekly for 8 wk) without serious adverse events. The progression-free survivals for the two patients were 1.9 and 4.1 months. Their overall survivals were 16.7 and 28.7 months. Although the efficacy was unclear, CIK cell infusion combined with other treatment strategies may have prolonged overall survival in refractory neuroblastoma patients. Further studies are needed to determine the exact role of CIK cell-based immunotherapy in relapsed or refractory neuroblastoma patients.
Cytokine-Induced Killer Cells* ; Disease-Free Survival ; Humans ; Immunotherapy* ; Immunotherapy, Adoptive ; Neuroblastoma*

Spontaneous rupture with internal bleeding of solid tumors has rarely been described at the time of diagnosis or during chemotherapy. This rare event must be regarded as a life threatening condition. In these emergency situations, control of hemorrhage, which is life-saving, can be achieved by transcatheter arterial embolization (TAE) and/or surgical resection. This report describes two infants presenting with acute hemorrhagic shock due to spontaneous tumor rupture of hepatoblastoma and neuroblastoma during chemotherapy. TAE successfully arrested the tumor bleeding and a visibly reduced the tumor size in both children. Spontaneous rupture of solid tumors occur infrequently in children, but is a life threatening situation. Careful monitoring for the occurrence of this rare event especially in very young children presenting with a large tumor mass.
Child ; Diagnosis ; Drug Therapy ; Emergencies ; Hemorrhage ; Hepatoblastoma ; Humans ; Infant ; Neuroblastoma ; Rupture ; Rupture, Spontaneous ; Shock, Hemorrhagic

Transient myeloproliferative disorder (TMD) is similar to congenital leukemia, with leukocytosis, increased peripheral blast cells, and hepatomegaly in the neonatal period. Although TMD occurs only in patients with Down syndrome and trisomy 21 mosaicism, there have been reports of congenital leukemia with trisomy 21 limited to hematopoietic cells showing spontaneous resolution. We identified trisomy 21 in the leukemic cells in a patient with congenital leukemia. As there was no other gene abnormality, we stopped chemotherapy, and the disease resolved spontaneously. We reviewed the cases of clonal trisomy 21 TMD and found that their clinical features were similar to those of TDM associated with Down syndrome. In conclusion, in a phenotypically normal patient with suspected congenital leukemia, it is necessary to confirm the presence of 21 trisomy. If the neonate has only trisomy 21 without other gene abnormalities, intensive chemotherapy may not be required.
Chromosomes, Human, Pair 21 ; Down Syndrome* ; Drug Therapy ; GATA1 Transcription Factor ; Hepatomegaly ; Humans ; Infant ; Infant, Newborn* ; Leukemia ; Leukocytosis ; Mosaicism ; Myeloproliferative Disorders* ; Trisomy*

Unprovoked deep vein thrombosis (DVT) is uncommon in pediatric patients and, among those, combined hereditary thrombophilia is particularly rare. We present a 9-year-old Korean boy who developed lower extremity pain with swelling, and was diagnosed with unprovoked DVT due to hereditary (combined hereditary thrombophilia). Coagulation test revealed antithrombin III and protein S deficiency. The genetic work up confirmed the first case of combined antithrombin III deficiency and protein S deficiency by SERPINC1 heterozygous termination mutation [c.685C>T (p.Arg229*)] and PROS1 heterozygous missense mutation [c.1597G>A (p.Val533Met)]. He was treated with continuous heparin and catheter intervention but those were ineffective or transiently effective. His DVT gradually improved only after prolonged anticoagulation.
Antithrombin III Deficiency ; Antithrombin III* ; Catheters ; Child ; Heparin ; Humans ; Lower Extremity ; Male ; Mutation, Missense ; Protein S Deficiency* ; Protein S* ; Thrombophilia* ; Venous Thrombosis*

Spinal epidural hematoma (SEH) is a rare neurosurgical emergency in which pressure on the spinal cord leads to acute neurological deficits, and is a rare complication in children with hemophilia. We report three cases of SEH in severe hemophilia A. An 8-month-old boy who presented with non-traumatic acute-onset irritability was found to have SEH and was later diagnosed with hemophilia. The two other patients presented with neck pain and magnetic resonance imaging confirmed the diagnosis of SEH. Two patients who received conservative management fully recovered, however the patient who presented with progressive neurological abnormalities at the time of diagnosis, received surgery but later developed breathing difficulties and quadriplegia. Early diagnosis and immediate, aggressive, clotting factor replacement therapy are crucial when managing SEH in children with hemophilia. Immediate and aggressive factor replacement, accompanied by both neurological monitoring and early imaging, are essential for hemophiliac with suspected SEH.
Child* ; Diagnosis ; Early Diagnosis ; Emergencies ; Hematoma ; Hematoma, Epidural, Spinal* ; Hemophilia A* ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neck Pain ; Quadriplegia ; Respiration ; Spinal Cord

Aplastic anemia may develop secondary to environmental exposure to entities such as chemicals, medical drugs, and infectious agents. Fatal complications from antiepileptic medications may occur despite careful and appropriate use. We report the case of a 9-year-old girl with a presenting diagnosis of aplastic anemia following treatment with ethosuximide for absence seizures. Aplastic anemia can now be cured with stem cell transplantation or immunosuppressive therapy. In this case, however, because of the impossibility of bone marrow transplantation and the specific needs of the patient's parents, three courses of methylprednisolone pulse therapy were administered. Following the therapy, there was improvement in pancytopenia and complete remission in the bone marrow. No adverse side effects of therapy were observed. The authors suggest that methylprednisolone pulse therapy may be a treatment for acquired aplastic anemia.
Anemia, Aplastic* ; Anticonvulsants ; Bone Marrow ; Bone Marrow Transplantation ; Child ; Diagnosis ; Environmental Exposure ; Epilepsy, Absence ; Ethosuximide ; Female ; Humans ; Methylprednisolone* ; Pancytopenia ; Parents ; Stem Cell Transplantation

Cytomegalovirus is a common virus that is mostly asymptomatic when infected, but rarely causes life-threatening hemolysis especially in immunocompromised children. We report a case of antiglobulin test negative severe hemolytic anemia caused by cytomegalovirus infection developed in an immune competent 9-year-old girl. The patient's hemoglobin level was 4.8 g/dL on the day of admission. The diagnosis was achieved by exclusion of other causes of hemolytic anemia and serological evidence of recent CMV infection. The patient was successfully treated with anti-viral agents and steroids resulting in recovery from anemia. Clinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in pediatric patients.
Anemia ; Anemia, Hemolytic* ; Child ; Coombs Test* ; Cytomegalovirus ; Cytomegalovirus Infections ; Diagnosis ; Diagnosis, Differential ; Female ; Hemolysis ; Humans ; Steroids

BACKGROUND: NUP98 has numerous partner genes of which plant homeodomain (PHD) finger protein 23 (PHF23) fusion with NUP98 (NP23) can be detected by RT-PCR in patients with cytogenetically normal acute myelogenous leukemia (AML). In this fusion transcript of NP23 PHD of PHF23 is known to specifically bind H3K4me3 residues and act as a chromatic modifier. Disulfiram (DSF) which inhibits the binding of PHD to H3K4me3 residues selectively killed NP23 myeloblasts in vitro and therefore, we planned to evaluate the efficacy of DSF in vivo. METHODS: Cultured 961C cells (CD45.2), NP23 myeloblast cells were transplanted into B57BL/6 mice (CD45.1). Using limit dilution assay the number of leukemic stem cells (LSCs) could be calculated. A certain amount of 961C cells were transplanted into B57BL/6 mice and DSF was treated after 1 week. The engraftment level was monitored with CD45.2. Kaplan Meier survival curve was used to compare the survival between therapeutic and control group. RESULTS: 961C cells could be transplanted without radiation in recipient mice. Calculated LSC was estimated to be 1 out of 184 cells (95% CI range, 56–609). When treated with DSF of different doses and administration routes in 961C recipient mice no survival advantage of DSF was observed in 961C transplanted immunocompetent mouse, however it was evident that engraftment level was consistent in both groups. CONCLUSION: No survival advantage of DSF in 961C transplanted immunocompetent mouse was observed, however it was evident that 961C cells shared niche with normal hematopoietic stem cells (HSCs). We expect that 961C cells and transplanted recipient mice have the potential to be used as in vivo system for new drugs development as well as for research dealing with niche for normal HSCs and LSCs.
Animals ; Disulfiram ; Fingers ; Granulocyte Precursor Cells ; Hematopoietic Stem Cells* ; Humans ; In Vitro Techniques ; Leukemia, Myeloid, Acute ; Mice ; Plants ; Stem Cells

BACKGROUND: Pneumocystis is difficult to culture or detect in laboratory environments. Its ecology including the timing and method of transmission as well as environmental sources and communicability remain unclear. METHODS: We retrospectively evaluated the pattern and treatment outcome of Pneumocystis jirovecii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL) who received chemotherapy. RESULTS: A total of 56 patients with ALL were evaluated. While on chemotherapy, all patients received PCP prophylaxis. PCP were found in a total of 6 patients, including definite PCP in 2, probable PCP in 2, and possible PCP in 2 patients. There were no significant differences in sex, age group, National Cancer Institute risk group, or pneumocystis prophylaxis type between PCP and non-PCP groups. However, there was a significant statistical difference in the times of ALL diagnosis. Regarding recent chemotherapy at the time of PCP diagnosis, there were one induction, one consolidation, and four maintenance cases. All PCP patients were treated with high-dose sulfamethoxazole (100 mg/kg/day) and trimethoprim (20 mg/kg/day) intravenously. Five patients survived, while one patient with endotracheal mechanical ventilation therapy died due to respiratory failure in spite of aggressive treatment. CONCLUSION: Pediatric PCP became extremely rare due to routine prophylaxis in clinical practice of pediatric malignancy. Nevertheless, we analyzed patients with acute lymphoblastic leukemia who had received PCP prophylaxis for 14 years, and analyzed the clustered outbreaks of PCP. It is still important to emphasize the need for prophylaxis and to increase the level of attention and isolation under environmental and personal risk factors.
Child ; Compliance ; Diagnosis ; Disease Outbreaks ; Drug Therapy ; Ecology ; Humans ; Methods ; National Cancer Institute (U.S.) ; Pneumocystis jirovecii ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Respiration, Artificial ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Sulfamethoxazole ; Treatment Outcome ; Trimethoprim

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a very rare disease and patients who do not receive timely treatment suffer from bleeding, infection, and malignancy. Hematopoietic stem cell transplantation (HSCT) has been recognized as an effective treatment, but the standard transplantation protocol has not been established. We report the outcomes of WAS patients who underwent HSCT in our institution. METHODS: We retrospectively studied patients who underwent HSCT at Seoul National University Children's Hospital from 2005 to 2018. Busulfan-based myeloablative conditioning regimen was used, and an intensive daily therapeutic drug monitoring (TDM) for busulfan dosing was started for effective myeloablation and to reduce toxicity since 2008. We collected and analyzed data regarding symptoms, engraftment, transplantation-related toxicities, and survival. RESULTS: Six WAS patients who received HSCT were evaluated. The median age of the patients at diagnosis was 5 years (range, 1–11). There were 2 matched unrelated donor bone marrow transplantations, 3 matched unrelated peripheral blood stem cell transplantations (PBSCT), and 1 haploidentical PBSCT. No patient experienced engraftment failure. Three patients developed grades II to IV acute graft-versus-host disease (GVHD). Two patients had veno-occlusive disease (VOD). Two patients died (due to VOD and acute GVHD). The 5-year overall survival was 66.7% with 8 years of median follow-up. Particularly, a patient who underwent haploidentical PBSCT using targeted busulfan is alive with a follow-up duration of 3 years after HSCT. CONCLUSION: In conclusion, WAS patients may be cured with HSCT with targeted busulfan-based myeloablative conditioning. But, long-term and multi-center studies are needed.
Bone Marrow ; Busulfan ; Diagnosis ; Drug Monitoring ; Follow-Up Studies ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Hemorrhage ; Humans ; Rare Diseases ; Retrospective Studies ; Seoul ; Stem Cell Transplantation ; Unrelated Donors ; Wiskott-Aldrich Syndrome