Efficacy of Paclitaxel in a Patient with Inoperable Pulmonary Vein Leiomyosarcoma.

Pulmonary vein leiomyosarcoma is extremely rare and has a poor prognosis. Surgical resection with a wide margin seems to offer the only chance of cure. The role of adjuvant therapy is controversial, and the exact efficacy of chemotherapy has not been observed. In this report, we present an 18-year-old male patient with pulmonary vein leiomyosarcoma in whom the use of paclitaxel (PAX) proved to be effective. Because the tumor originated from the left superior pulmonary vein and diffused into the left atrial wall and the junction of the right superior pulmonary vein and left atrium, the en bloc excision of the tumor was impossible. The first-line chemotherapy, including ifosfamide, doxorubicin, and dacarbazine, in conjugation with radiation therapy could not demonstrate any effect on the tumor size. However, the following PAX-containing regimen provided complete regression of the tumor. After PAX-based high-dose chemotherapy with autologous peripheral blood stem cell transplantation, the patient showed complete remission for 2 years. Although he suffered metastatic recurrences and died 4 years after the onset of symptoms, our patient's clinical course clearly reveals the efficacy of PAX.

Variations in ORAI1 Gene Associated with Kawasaki Disease.

Kawasaki disease (KD; MIM#61175) is a systemic vasculitis syndrome with unknown etiology which predominantly affects infants and children. Recent findings of susceptibility genes for KD suggest possible involvement of the Ca(2+)/NFAT pathway in the pathogenesis of KD. ORAI1 is a Ca(2+) release activated Ca(2+) (CRAC) channel mediating store-operated Ca(2+) entry (SOCE) on the plasma membrane. The gene for ORAI1 is located in chromosome 12q24 where a positive linkage signal was observed in our previous affected sib-pair study of KD. A common non-synonymous single nucleotide polymorphism located within exon 2 of ORAI1 (rs3741596) was significantly associated with KD (P = 0.028 in the discovery sample set (729 KD cases and 1,315 controls), P = 0.0056 in the replication sample set (1,813 KD cases vs. 1,097 controls) and P = 0.00041 in a meta-analysis by the Mantel-Haenszel method). Interestingly, frequency of the risk allele of rs3741596 is more than 20 times higher in Japanese compared to Europeans. We also found a rare 6 base-pair in-frame insertion variant associated with KD (rs141919534; 2,544 KD cases vs. 2,414 controls, P = 0.012). These data indicate that ORAI1 gene variations are associated with KD and may suggest the potential importance of the Ca(2+)/NFAT pathway in the pathogenesis of this disorder.

Early-onset hemophagocytic lymphohistiocytosis after the start of chemotherapy for advanced neuroblastoma.

The authors report the clinical course of a 3-year-old boy with stage 4 neuroblastoma (NB) complicated by hemophagocytic lymphohistiocytosis (HLH) immediately after the start of chemotherapy. The NB responded very well to the chemotherapy, but the patient developed high fever on the 2nd day, and was diagnosed as having HLH of the 7th day of chemotherapy. No infections were demonstrated, and massive tumor cell destruction resulting from the rapid effect of chemotherapy was thought to be a cause of systemic cytokine response, resulting in HLH. Methylprednisolone pulse therapy was effective for the HLH, which did not recur thereafter. HLH should be recognized as a serious adverse event during chemotherapy for advanced NB that has a large malignant cell load.

Primary anaplastic large cell lymphoma of the psoas muscle: a case report and literature review.

Primary anaplastic large cell lymphoma (ALCL) of skeletal muscle is very rare. We report a case of ALCL arising from the left psoas muscle. A 14-year-old girl presented with a large left inguinal tumor. She complained of a 2-month history of left leg pain, which had been exacerbated upon leg extension, and she had become aware of a rapidly growing left inguinal tumor 3 weeks before admission. CT scan and MRI revealed a large tumor arising from the left major psoas muscle and protruding into the inguinal region. In view of the tumor's location and the patient's age, soft tissue tumors such as rhabdomyosarcoma and primitive neuroectodermal tumor were initially considered. However, histopathological examination yielded a diagnosis of anaplastic lymphoma kinase-positive ALCL. The serum level of soluble interleukin-2 receptor was markedly elevated at 50,414 U/ml, and this also strongly suggested ALCL. Although rarely reported, ALCL is an important entity to consider in the differential diagnosis of skeletal muscle tumors in children and young adults.

Cytotoxic T-lymphocyte-associated antigen 4 gene polymorphisms in Japanese children with infection-associated hemophagocytic lymphohistiocytosis.

OBJECTIVE: This study examined whether genetic polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of T cells, are associated with infection-associated hemophagocytic lymphohistiocytosis (IHLH) in Japanese children. METHODS: We investigated the alleles of four polymorphisms in the CTLA-4 gene [-318CT, +49AG, CT60 and a dinucleotide repeat length polymorphism (AT)n] in 43 Japanese children with IHLH and 100 healthy Japanese controls. The hyper-polymorphic (AT)n alleles were divided into two types; the shortest allele (designated as AT(7)) and the longer alleles (designated as AT(>)(7)). RESULTS: A significant difference in the distribution of the (AT)n genotype was found between patients and controls (p = 0.028). Also, the frequency of the AT(>)(7) allele was significantly higher in the patients with IHLH than in the controls (p = 0.007). No significant linkage disequilibrium was found between each polymorphism. With regard to laboratory data, patients homozygous for the CTLA-4 AT(>)(7) allele showed significantly higher serum levels of lactate dehydrogenase and soluble interleukin-2 receptor than patients with the other alleles. CONCLUSION: These results suggest that CTLA-4 polymorphisms might play a role in the development of IHLH in Japanese children.

Clinical assessment of Mycoplasma pneumoniae-associated hemophagocytic lymphohistiocytosis.

BACKGROUND: Mycoplasma pneumoniae has been reported to be an etiologic pathogen of infection-associated hemophagocytic lymphohistiocytosis (HLH), but few case reports have been available to date. METHODS: The clinical features of four childhood cases of M. pneumoniae-associated hemophagocytic lymphohistiocytosis (Mp-HLH) were retrospectively assessed to obtain data that might be useful for early diagnosis and effective management. The previous English-language literature pertaining to Mp-HLH was also reviewed. RESULTS: The patients were two boys and two girls, aged between 1 and 11 years of age. One patient was demonstrated to have concurrent infection with rubella. All the patients had typical radiographic features of M. pneumoniae pneumonia, and one patient also had encephalopathy as a complication. All the children underwent bone marrow examination because of antibiotic-refractory fever, mild hepatosplenomegaly, cytopenia, hyperferritinemia and elevated levels of urine beta2-microglobulin. Cytopenia and hepatosplenomegaly in the present patients were relatively mild as compared to those in cases of other infection-associated HLH such as Epstein-Barr virus infection-associated HLH. Treatment with corticosteroids resulted in prompt and complete resolution in two cases, and i.v. high-dose gammaglobulin therapy achieved a complete response in another child. Spontaneous resolution under treatment with antibiotics alone was observed in one case. CONCLUSION: Although Mp-HLH is a rare complication of M. pneumoniae infection, it should always be considered in patients with antibiotic-refractory M. pneumoniae infections with cytopenia. Mp-HLH might be effectively treated by corticosteroids or high-dose gammaglobulin. To clarify the diverse clinical manifestations of M. pneumoniae infections, immunological interactions between M. pneumoniae and the host immune system should be further investigated.

Non-myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma.

The prognosis of patients with relapsed osteosarcoma is dismal despite the use of intensive chemotherapy. We describe a patient with refractory osteosarcoma who underwent non-myeloablative peripheral blood stem cell transplantation (PBSCT) from an human leukocyte antigen (HLA)-identical sibling during a third complete remission. The patient suffered pulmonary relapse after the transplantation. Cyclosporin A withdrawal induced a graft-vs.-osteosarcoma effect and graft-vs.-host disease, but eventually the tumor progressed. Although our experience in this case suggested the presence of a graft-vs.-osteosarcoma effect during non-myeloablative allogenic PBSCT, this strategy might have limited value for refractory osteosarcoma with rapid growth kinetics.

Helicobacter pylori infection in children with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Recently a high prevalence of Helicobacter pylori infection has been reported in adult patients with chronic idiopathic thrombocytopenic purpura (cITP). Furthermore, after H. pylori eradication therapy in such patients, their platelet counts have been observed to increase, suggesting that H. pylori may be a causative agent of adult cITP. However, there have been only a few reports of children with cITP. The purpose of the present paper was to examine the association between H. pylori infection and cITP in Japanese children. METHODS: Helicobacter pylori stool antigens (HpSA) were measured and the prevalence of H. pylori infection was determined in 10 children with cITP. RESULTS: Helicobacter pylori infection was found in only two of the subjects. In a boy, the urea breath test (UBT) was also positive and the patient received eradication therapy using amoxicillin, clarithromycin, and lansoprazole for 1 week. The therapy was successful and the patient's platelet count increased. The response was maintained throughout more than 1 year of follow up. CONCLUSIONS: The prevalence of H. pylori infection in children with cITP is not high. However, the platelet count increased after eradication therapy in a boy with cITP. It is suggested that the eradication of H. pylori infection would be valuable in children, as well as in adults, with cITP.

Macrophage activation syndrome in children with systemic-onset juvenile chronic arthritis.

Macrophage activation syndrome (MAS) is a life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile chronic arthritis (SOJCA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study assessed the clinical features of nine MAS events in five children with SOJCA. Nonremitting fever and decreased platelet and white blood cell counts led to a diagnosis of MAS. The urinary beta2-microglobulin (beta2MG) level was a sensitive indicator of MAS. Serum levels of beta2MG and soluble interleukin-2 receptor were also elevated. These biologic markers reflecting hyperactivated cellular immunity are useful indicators of MAS. Four children treated with cyclosporin A (CSP) achieved rapid and complete recovery, but one patient without CSP died due to rapidly progressive respiratory failure. All children treated with CSP responded quickly, and fever abated within 36 h of initiation of treatment. CSP should be added to first-line therapy of MAS.

Central hypothyroidism in infants who were born to mothers with thyrotoxicosis before 32 weeks' gestation: 3 cases.

We describe 3 infants who were born to mothers with Graves' disease and developed central hypothyroidism that persisted for >6 months after birth. Two were preterm infants, and the other was a term infant who was born to a euthyroid mother who had been treated with an antithyroid drug since week 31 of gestation. These cases suggest that passage of thyroid hormones can occur from a thyrotoxic mother to the fetus and that the gestational period earlier than 32 weeks may be the critical time for development of central hypothyroidism.

Severe hypercalcemia in a child with acute nonlymphocytic leukemia: the role of parathyroid hormone-related protein and proinflammatory cytokines.

Among the hematological malignancies, hypercalcemia has often been reported in lymphoid malignancies such as multiple myeloma and adult T cell leukemia/lymphoma, but it has only rarely been described in acute nonlymphocytic leukemia. We describe here a 14-month-old girl with acute monocytic leukemia complicated by severe hypercalcemia (4.6 mmol/l) at presentation. A bone survey showed generalized bone resorption, but no localized osteolytic lesions. A search for the etiology of the hypercalcemia revealed that the serum levels of parathyroid hormone-related protein (PTHrP) and also proinflammatory cytokines with stimulatory effects on osteolytic bone resorption - TNF-alpha, IL-6 and M-CSF - were elevated. The patient achieved complete remission with induction chemotherapy, and the levels of PTHrP and the cytokines became normalized. In this case, PTHrP and cytokines might have acted cooperatively to exacerbate bone resorption, resulting in severe hypercalcemia.

Fatal pulmonary thromboembolism after a second course of high-dose chemotherapy with autologous peripheral blood stem cell transplantation.

We describe a 4-yr-old boy with an occult primitive neuroectodermal tumor, who suffered fatal PTE after a second course of HDC with autologous PBSCT. On day + 52 after a second PBSCT, he was admitted because of respiratory distress. Respiratory failure rapidly progressed and he died within 4 days. The diagnosis of PTE was confirmed by a lung perfusion study with technetium-99m macroaggregated albumin, but too late to allow treatment. Although rare, PTE must be recognized as an important differential diagnosis when respiratory symptoms are observed after HDC with PBSCT.