Takeshi Higa

Childhood blastic NK cell leukemia successfully treated with L-asparagenase and allogeneic bone marrow transplantation

Blastic NK cell lymphoma/leukemia is a rare and highly malignant neoplasia in both adults and children. It is characterized by lymphoblastoid morphology without cytoplasmic granules and immature NK cell immunophenotypes (CD56+, CD57−, CD16−). It has predilection for extranodal organ involvement, and the prognosis of affected patients is extremely poor under the current chemotherapy. We present a 14‐year‐old girl who was diagnosed as having blastic NK cell leukemia with mediastinal, pleural, and pericardial involvement. Immunophenotyping of her leukemic cells showed positive for CD2, CD5, CD7, CD34, CD56, HLA‐DR, and cytoplasmic CD3. T cell receptor (TCR) and Immunoglobulin heavy chain genes were not rearranged. She received chemotherapy for acute lymphoblastic leukemia incorporating L‐asparaginase (L‐asp) which successfully induced complete remission. Bone marrow transplantation (BMT) from her HLA‐identical sibling was conducted after two courses of consolidation therapy. Expression of aspargine synthetase (AS) protein in the leukemic cells at diagnosis was examined by an immunocytochemical method. She remains in hematological remission for over 36 months after BMT. The expression of AS protein was negative, suggesting that the leukemic cells were sensitive to L‐asp. Induction and consolidation therapy incorporating L‐asp followed by allo‐BMT might be a promising treatment for child hood blastic NK cell leukemia, but more samples of the rare leukemia need to be studied before any definitive conclusions can be drawn.

Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipients lymphocytes reached almost half of normal level within two years after BMT. For the successive 9 + years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donors, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA.

Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study.

The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high‐dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS).

Germline Mutation of CBL Is Associated With Moyamoya Disease in a Child With Juvenile Myelomonocytic Leukemia and Noonan Syndrome‐Like Disorder

Germline mutations in CBL have been identified in patients with Noonan syndrome‐like phenotypes, while juvenile myelomonocytic leukemia (JMML) harbors duplication of a germline CBL, resulting in acquired isodisomy. The association between moyamoya disease and Noonan syndrome carrying a PTPN11 mutation has recently been reported. We present a patient with JMML who developed moyamoya disease and neovascular glaucoma. Our patient exhibited a Noonan syndrome‐like phenotype. Genetic analysis revealed acquired isodisomy and a germline heterozygous mutation in CBL. This is a rare case of CBL mutation associated with moyamoya disease. Prolonged RAS pathway signaling may cause disruption of cerebrovascular development. Pediatr Blood Cancer 2015;62:542–544.

Possible involvement of IL-6-producing tissue-resident macrophages in early-onset pericardial effusion pathogenesis after hematopoietic stem cell transplantation

Pericardial effusion (PE) is a potentially life‐threatening complication following hematopoietic stem cell transplantation (HCT). A higher incidence of early‐onset PE, unrelated to graft‐versus‐host disease, before day 100 after HCT has been reported in pediatric patients, but the pathogenic mechanism is poorly understood. Aiming to determine the pathogenesis of early‐onset PE in pediatric patients, we analyzed the cytokine concentration and cell population in the pericardial fluid of four pediatric patients with PE.

Prophylactic use of octreotide for asparaginase-induced acute pancreatitis

In the present study, we sought to evaluate the prophylactic use of octreotide for asparaginase-induced acute pancreatitis. We reviewed the medical records of seven patients in two institutions who received prophylactic octreotide for re-administration of asparaginase after asparaginase-induced acute pancreatitis. Three patients completed asparaginase treatment without developing pancreatitis, and four experienced recurrence of pancreatitis. A literature search using PubMed identified four additional patients in whom asparaginase was successfully re-administered with octreotide. Prophylactic use of octreotide may, thus, be warranted for patients who would benefit from re-administration of asparaginase for cancer treatment; however, careful observation is needed to monitor for breakthrough recurrence of pancreatitis.

Sarcomatoid Carcinoma of the Bladder in a Child: Case Report of a Successful Treatment Including Gemcitabine and Cisplatin

This report describes an unusual case of sarcomatoid carcinoma of the bladder in a 3-year-old girl. Although saving the patients life is most essential, it is also essential to consider quality of life. The patient underwent neoadjuvant chemotherapy with gemcitabine and cisplatin for bladder preservation. The tumor considerably decreased in size. After 4 courses of chemotherapy, the patient underwent a partial cystectomy followed by postoperative irradiation with 2 courses of chemotherapy. Seventy months after the operation, she remains alive, showing complete remission with normal bladder function. Chemotherapy resulted in tumor shrinkage and allowed for bladder preservation.