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Hiroshi Tsujimoto, Shinji Kounami, Takayuki Ichikawa, Taketsugu Hama, Hiroyuki SuzukiDepartment of Pediatrics, Wakayama Medical University, Wakayama, JapanCorrespondence: Hiroshi TsujimotoDepartment of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama City 641-8509, JapanTel +81 73 441 0633Fax +81 73 444 9055Email tujimoto@wakayama-med.ac.jpPurpose: Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal hyperinflammatory disorder. For further understanding of the pathogenesis of HLH, we examined serum levels of high mobility group box protein 1 (HMGB1) in children with HLH.Patients and methods: Serum HMGB1 levels were measured in 28 patients with HLH and 6 normal controls using a quantitative enzyme-linked immunosorbent assay. The patients were 21 boys and 7 girls, aged from 10 days to 21 years, with a median age of 8.5 years. The underlying conditions of HLH were infection-associated HLH in 18 patients, malignancy-associated HLH in 7 patients, and genetic HLH in 3 patients. The relations between serum HMGB1 levels and clinical symptoms and laboratory parameters were analyzed.Results: Serum HMGB1 levels were significantly higher in patients with HLH than in normal controls (median, 6.5 ng/mL, interquartile range, 4.25–13.1). The serial serum HMGB1 levels in one patient fell to reflect the disease activity. Serum HMGB1 levels were significantly higher in patients with disseminated intravascular coagulation (DIC) than in patients without DIC (p

Background and Objectives: Granulocyte transfusion (GTX) is a treatment option for severe infections in patients with neutropenia. In previous studies, hydroxyethyl starch (HES) was used to enhance red blood cell sedimentation for granulocyte collection (GC). However, there are safety concerns about HES, and HES is not readily available in some countries. Therefore, we compared the granulocyte counts and GC efficiency achieved by two apheresis systems without HES., Materials and Methods: All consecutive GC procedures performed between July 2011 and March 2018 at our hospital were analysed. COBE Spectra was used until 5 February 2016, and Spectra Optia was used afterwards. HES was not used., Results: Twenty-six GC procedures were performed, including 18 performed using COBE Spectra and 8 using Spectra Optia. When Spectra Optia was used, >1 × 10 10 neutrophils were collected from seven of the eight (88%) procedures. Although there was no significant difference in the granulocyte yield between COBE Spectra-based and Spectra Optia-based GC procedures, the collection efficiency of Spectra Optia was significantly higher than that of COBE Spectra (p = 0.021). Furthermore, the granulocyte yields of Spectra Optia-based GC tended to be more strongly correlated with the peripheral blood neutrophil count on the day of apheresis than those of COBE Spectra-based GC., Conclusion: Our results suggest that Spectra Optia achieves greater GC efficiency than COBE Spectra, even without HES. GTX may be a therapeutic option for severe neutropenia, even in places where HES is not available., (© 2023 International Society of Blood Transfusion.)

A huge abdominal cystic lesion with ascites was detected in a male neonate at 31 weeks of gestation. Increasing ascites and the appearance of subcutaneous edema were detected, which caused fetal hydrops. The patient was delivered by emergency cesarean section at 33 weeks of gestation. The birth weight was 2,407 g, and the Apgar score was 8/9 points (1-/5-min values). Breathing at birth was stable, but the patient presented with remarkable abdominal distention due to the ascites. Later, the patient presented with tachypnea, and breathing gradually worsened, so an emergency operation was performed. There were no intraoperative findings within the small intestine, but there was a large amount of ascites and a cystic mass arising from the liver. The patient's breathing and circulation dynamics could only be stabilized by ascites removal, so only a tumor biopsy was performed. The pathological findings led to the diagnosis of an inflammatory myofibroblastic tumor, and steroids were administered early after surgery for the purpose of an anti-inflammatory effect and tumor shrinkage. The abdominal distention was alleviated, and blood examinations showed a reduced inflammatory response. There was no apparent shrinkage of the tumor, however; thus, radical surgical treatment was performed on day 24. The postoperative course was uneventful, so the patient was discharged on day 36. Seven years after the operation there has been no recurrence or distant metastasis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Acute lymphoblastic leukemia (ALL) presenting as Fanconi syndrome (FS) is extremely rare. Here, we report a case of ALL presenting as bilateral nephromegaly following FS. A 2-year-old girl was unexpectedly diagnosed with bilateral nephromegaly. After 2 weeks, she developed general fatigue, thirst, and polyuria. Laboratory examinations revealed renal tubular acidosis, hypokalemia, hypophosphatemia, and aminoaciduria, and FS was diagnosed. Replacement of bicarbonate and potassium did not improve her condition. Two weeks after the onset of FS, leukemic cells appeared on a peripheral blood smear, and the patient was diagnosed with precursor B-cell ALL presenting as nephromegaly and FS. Chemotherapy brought about a prompt resolution of acidosis and electrolyte abnormalities, without renal dysfunction. The patient remains well 4 years after the onset of the disease. Although extremely rare, FS should be recognized as one of the emerging renal complications of ALL.

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.

Neonatal acute megakaryoblastic leukemia (AMKL) without Down syndrome (DS) is an extremely rare disorder. We report of a one-day-old male infant without DS who developed AMKL with leukemia cutis and right facial nerve palsy. Magnetic resonance imaging of the patient's brain revealed multiple intracranial tumors. A biopsy specimen of the skin lesion was suggestive of AMKL, but the bone marrow leukemic cells were less than 5% of the marrow nucleated cells. The skin and intracranial lesions had spontaneously regressed within one and a half months, but the patient's anemia and thrombocytopenia gradually worsened and the leukemic cells in the bone marrow gradually increased to more than 20% of the nucleated cells. In addition, multiple intracranial lesions reappeared at 72 days of life. We diagnosed the patient with AMKL, and chemotherapy followed by unrelated cord blood transplantation after a reduced-intensity conditioning regimen resulted in sustained complete remission. At present, the patient is well, and he has demonstrated normal development for five years.

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 (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., (Copyright © 2012 S. Karger AG, Basel.)

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.

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.

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., (Copyright 2005 S. Karger AG, Basel)

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.

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.

Various kinds of second malignant neoplasms after sucessful treatment for childhood acute leukemia have been reported. The authors describe an unusual case of an olfactory neuroblastoma in a patient previously treated for childhood acute leukemia including autologous bone marrow transplantation. The prophylactic cranial irradiation and the total body irradiation during autologous bone marrow transplantation may have induced the development of their patient's olfactory neuroblastoma. Although a second primary olfactory olfactory neuroblastoma is rare is rare, it should be added to the list of second malignant neoplasms in the sinonasal region.

We report a case of transient abnormal myelopoiesis (TAM) with Down's syndrome. As the blast cells had additional chromosome abnormalities (50,XY,+12,+14,+21 x 2), a possibility of acute leukemia was considered from a cytogenetic point of view. But the abnormal clone gradually disappeared without antileukemic therapies. Viewing it together with previous reports of TAM with additional chromosome abnormalities in Down's syndrome babies, its presence does not immediately indicate an aggressive clinical course as in acute leukemia and spontaneous complete hematological remission may be achieved. Thus, a careful follow-up should precede cytogenetic findings helping to determine the therapeutic intervention.