-
[show abstract]
[hide abstract]
ABSTRACT: Familial platelet disorder with a propensity to develop acute myeloid leukemia (FPD/AML) is a rare autosomal dominant disease characterized by thrombocytopenia, abnormal platelet function, and a propensity to develop myelodysplastic syndrome (MDS) and AML. So far, > 20 affected families have been reported. Recently, a second RUNX1 alteration has been reported; however, no additional molecular abnormalities have been found so far. We identified an acquired CBL mutation and 11q-acquired uniparental disomy (11q-aUPD) in a patient with chronic myelomonocytic leukemia (CMML) secondary to FPD with RUNX1 mutation but not in the same patient during refractory cytopenia. This finding suggests that alterations of the CBL gene and RUNX1 gene may cooperate in the pathogenesis of CMML in patients with FPD/AML. The presence of CBL mutations and 11q-aUPD was an important "second hit" that could be an indicator of leukemic transformation of MDS or AML in patients with FPD/AML.
Blood 12/2011; 119(11):2612-4. · 9.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The influence of central nervous system (CNS)-directed chemotherapy on intelligence remains controversial. In this study, we investigated the influence of treatment on intellectual development in acute lymphoblastic leukemia (ALL) and brain tumor patients undergoing CNS-directed treatments.
Among patients treated in the Department of Pediatrics, St Luke's International Hospital between April 2000 and March 2009, the subjects were 38 patients with ALL or brain tumors who underwent regular Wechsler intelligence tests.
The subjects consisted of 26 patients with ALL and 12 with brain tumors. Prophylactic cranial irradiation was not performed in patients with ALL, whereas it was done for all those with brain tumor. In patients with ALL, the IQ 1 year later was not changed from the start of treatment. In those with brain tumors, the verbal IQ 1 year later was significantly lower than that at the start of treatment. In patients with ALL, intelligence tests were performed 3 years after the start of treatment and there were no marked changes between the two time-points (n = 11). In those with a brain tumor, intellectual functions further decreased after the completion of treatment to as late as 5 years after the initiation of treatment (n = 7).
There is no intellectual impairment in any patient with ALL at post-treatment follow-up 3 years after the start of treatment, while intelligence is serially reduced in brain tumor patients. An innovative intervention may be needed for this group of patients.
Pediatrics International 03/2011; 53(5):694-700. · 0.63 Impact Factor
-
Hiroaki Goto,
Takeshi Inukai,
Hiroyasu Inoue, Chitose Ogawa,
Takashi Fukushima,
Miharu Yabe,
Akira Kikuchi,
Kazutoshi Koike,
Keitaro Fukushima,
Keiichi Isoyama,
Tomohiro Saito,
Akira Ohara,
Ryoji Hanada,
Jiro Iwamoto,
Noriko Hotta,
Yoshihisa Nagatoshi,
Jun Okamura,
Masahiro Tsuchida
International journal of hematology 03/2011; · 1.17 Impact Factor
-
Hiroaki Goto,
Takeshi Inukai,
Hiroyasu Inoue, Chitose Ogawa,
Takashi Fukushima,
Miharu Yabe,
Akira Kikuchi,
Kazutoshi Koike,
Keitaro Fukushima,
Keiichi Isoyama,
Tomohiro Saito,
Akira Ohara,
Ryoji Hanada,
Jiro Iwamoto,
Noriko Hotta,
Yoshihisa Nagatoshi,
Jun Okamura,
Masahiro Tsuchida
[show abstract]
[hide abstract]
ABSTRACT: The Tokyo Children's Cancer Study Group (TCCSG) and the Kyushu Yamaguchi Children's Cancer Study Group (KYCCSG) performed a collaborative analysis of data on children with Down syndrome and acute lymphoblastic leukemia (DS-ALL). Among the 1,139 patients who were enrolled in the TCCSG L99-15, L99-1502, or the KYCCSG ALL 96 study, 13 patients with newly diagnosed ALL had DS. In the DS patients, a significantly higher proportion of patients developed ALL at age 5 years or older compared with the non-DS ALL patients (P < 0.001). The 5-year relapse-free or overall survival of DS-ALL patients was 50.0 or 61.5%, respectively. Relapse accounted for all causes of death. In the TCCSG L99-15 cohort, the overall survival of DS-ALL patients was 42.9%, which was significantly worse compared with 87.9% in the non-DS population (P < 0.001). The survival of patients who received reduced-dose chemotherapy was significantly worse than those who received full-dose chemotherapy (P < 0.001). However, a higher dose of methotrexate was not associated with a better outcome. Results of our preliminary study suggest that the survival of DS-ALL patients could be improved by treatment without dose reduction if possible, although the appropriate dose of methotrexate for DS-ALL needs to be determined.
International journal of hematology 02/2011; 93(2):192-8. · 1.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Acute lymphoblastic leukemia (ALL) is known to cause several ocular involvements, but exudative retinal detachment is a rare complication. We describe a case report of a 4-year-old boy with T cell ALL who developed bilateral exudative retinal detachment caused by leukemic infiltration in the retinas after achieving hematological remission. Intravenous steroid pulse therapy and local irradiation reversed the condition, but it recurred concurrently with disease progression after a second relapse in the bone marrow. It is suggested that ophthalmic examination is crucial for ALL patients, especially for those whose white blood cell count is very high at onset.
International journal of hematology 10/2010; 92(3):535-7. · 1.17 Impact Factor
-
Shizuka Watanabe,
Kumiko Miyake, Chitose Ogawa,
Haruna Matsumoto,
Kenichi Yoshida,
Shinsuke Hirabayashi,
Daisuke Hasegawa,
Tadao Inoue,
Junko Kizu,
Reiko Machida,
Akira Ohara,
Ryota Hosoya,
Atsushi Manabe
[show abstract]
[hide abstract]
ABSTRACT: Patients with acute lymphoblastic leukemia (ALL), who develop antiasparaginase antibodies without clinical allergic reactions ("silent inactivation") during L: -asparaginase (L: -Asp) treatment, have poor outcomes. Ammonia is produced by hydrolysis of asparagine by L: -Asp. We postulated that plasma ammonia level might reflect the biological activity of L: -Asp. Five children with ALL treated according to the Tokyo Children's Cancer Study Group (TCCSG) protocol were enrolled. Plasma ammonia levels were analyzed immediately and 1 h after incubation at room temperature and "ex vivo ammonia production" was defined as increase in ammonia concentration. Ex vivo ammonia production well correlated with L: -Asp activity (r = 0.882, P < 0.01, n = 23). It always exceeded 170 microg/dL (170-345 microg/dL) in induction therapy. We found 3 patients whose ammonia production was negligible during later phases of therapy. Antiasparaginase antibody was detected and L: -Asp activity decreased in these patients. Ex vivo ammonia production is a surrogate marker of L: -Asp biological activity.
International journal of hematology 09/2009; 90(3):347-52. · 1.17 Impact Factor
-
Keitaro Arima,
Daisuke Hasegawa, Chitose Ogawa,
Itaru Kato,
Toshihiro Imamura,
Ayako Takusagawa,
Hiroka Takahashi,
Yoshiro Kitagawa,
Toshinari Hori,
Masahito Tsurusawa,
Atsushi Manabe,
Ryota Hosoya
[show abstract]
[hide abstract]
ABSTRACT: Testicular relapse has an impact on the prognosis of boys with acute lymphoblastic leukemia (ALL). Because isolated testicular relapse often precedes hematological relapse, systemic therapy is required in addition to local therapy. However, a rationale for the use of a combination of systemic chemotherapy and local therapy is unclear. A 12-year-old boy with T-ALL suffered from isolated testicular relapse at 27 months after diagnosis. He was successfully treated with systemic chemotherapy with orchiectomy and prophylactic irradiation to the contralateral testis. We retrospectively estimated the minimal residual disease in the bone marrow (BM) and the testis by detection of clone-specific T-cell receptor rearrangement of leukemic cells. We detected leukemic cells in the affected testis at relapse, as well as in the BM at initial diagnosis. In addition, we confirmed submicroscopic disease in the unaffected testis and the BM at relapse. We conclude that molecular analysis could reveal the submicroscopic disease in the patient with apparently isolated testicular relapse. This finding may provide a rationale for intensified systemic treatment of patients with isolated testicular relapse.
International journal of hematology 09/2009; 90(3):370-3. · 1.17 Impact Factor
-
Miharu Yabe,
Masahiro Sako,
Hiromasa Yabe,
Yuko Osugi,
Hidemitsu Kurosawa,
Taemi Nara,
Mika Tokuyama,
Souichi Adachi,
Chie Kobayashi,
Masakatsu Yanagimachi,
Yoshitoshi Ohtsuka,
Yozo Nakazawa, Chitose Ogawa,
Atsushi Manabe,
Seiji Kojima,
Tatsutoshi Nakahata
[show abstract]
[hide abstract]
ABSTRACT: A pilot study was undertaken using a myeloablative conditioning with fludarabine, busulfan, and melphalan to improve the outcome of HSCT in 10 children, aged six months to six yr, with JMML. All patients were conditioned with oral busulfan (560 mg/m(2)), fludarabine (120 mg/m(2)), and melphalan (180-210 mg/m(2)) prior to HSCT, and received stem cells from bone marrow in seven cases, and from cord blood in three cases. Engraftment was documented in eight patients, whereas graft failure occurred in two, one of whom had received HLA-mismatched cord blood and other had received bone marrow from HLA-mismatched mother. Three patients, including two in who graft failure had occurred, relapsed. Five patients developed acute GVHD and two developed chronic GVHD. Seven patients are alive and in remission 27-69 months after transplantation. Thus, our study showed that HSCT following conditioning with fludarabine, busulfan, and melphalan was well tolerated and appeared to be effective for JMML.
Pediatric Transplantation 05/2008; 12(8):862-7. · 1.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.
Pediatric Blood & Cancer 04/2008; 50(3):676-8. · 1.89 Impact Factor
-
Cancer Genetics and Cytogenetics 03/2008; 181(1):67-8. · 1.39 Impact Factor
-
Pediatrics International 05/2006; 48(2):181-4. · 0.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The success of allogeneic bone marrow transplantation (allo-BMT) in children with myelodysplastic syndrome (MDS) is mainly affected by relapse. The role of additional immunotherapy for pediatric patients with MDS relapsing after allo-BMT remains to be established. Because immunotherapy is generally more effective for patients who bear a low tumor burden, monitoring of minimal residual diseases (MRD) is essential for early diagnosis at molecular relapse. We report here that a patient with relapsed MDS after allo-BMT was successfully treated by the rapid discontinuation of immunosuppressive therapy at molecular relapse while monitoring Wilms tumor (WT1) gene expression levels. Quantitative analysis of WT1 gene expression appeared to be a useful tool to monitor MRD in the present case.
American Journal of Hematology 03/2006; 81(2):139-41. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study reports a 1-year-old boy with precursor B cell acute lymphoblastic leukemia (ALL) carrying t(16;21)(p11;q22). Reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequence analysis showed TLS/FUS-ERG chimeric mRNA with a novel junctional pattern of exon 7 of TLS/FUS and exon 6 of ERG. He did not respond to ALL-oriented therapy. Complete remission (CR) was achieved by chemotherapy oriented for acute myeloid leukemia. Allogenic bone marrow transplantation was done and he has been in CR for 24 months. TLS/FUS-ERG chimeric mRNA was not detected after CR. This is the first report of an ALL patient with a TLS/FUS-ERG fusion transcript.
Leukemia and Lymphoma 01/2006; 46(12):1833-5. · 2.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The treatment of massive osteolysis with lymphangioma and/or hemangioma (Gorham-Stout syndrome) has been controversial. The authors report on a patient with multiple massive osteolyses and extensive lymph-hemangiomatosis whose lesions were reduced by interferon alfa therapy. A 2-year-old girl had complained of left chylothorax. Thoracoscopy showed an increase in small lymphatic vessels in the chest wall. The chylothorax was improved by coagulation of the lymphatic vessels. Later, multiple massive osteolyses appeared in the left 11th and 12th ribs, the TH10-L3 vertebrae, and the right femur. There were also hemangiomas in the liver and spleen, a tumor lesion in the left lower chest wall, and hemangiomatous change on the skin surface of the left back. The left lung had only a minimal air content. After OK-432 was injected into the femur and chest wall lesions, the femur lesion disappeared. Then, as right chylothorax appeared, OK-432 was injected into the right pulmonary cavity. The chylothorax disappeared, but pericardial effusion appeared. After steroid pulse therapy, pericardial effusion disappeared. During these treatments, the 7th to 10th ribs disappeared from the x-ray and scoliosis developed. One month later, a cloudy fluid collection in the right lung was found on computed tomography. Interferon alfa and steroid pulse therapy were started. Interferon alfa (1,500,000 units) was subcutaneously administered daily for 2 months and was gradually reduced and maintained at 1,500,000 unit/wk. Steroids were also reduced and maintained at 5 mg/d of predonine. Later, the progress of osteolysis and the extension of lymph-hemangiomatosis stopped. Ten months later, hemangioma in the back disappeared, and the 7th to 10th ribs, which had disappeared, reappeared. The interferon alfa therapy was stopped 14 months after it was administered. The patient's condition has been stable for 10 months since then. At this time, computed tomography shows regression of the hemangiomatous lesion in the back. The authors clinically diagnosed the patient as having Gorham-Stout syndrome with extension of lymph-hemangiomatosis. Interferon alfa with or without steroid therapy should be a choice for patients with extension lesions.
Journal of Pediatric Surgery 04/2005; 40(3):E47-50. · 1.45 Impact Factor
-
Takashi Nitta,
Hidekazu Koike,
Yoshitatsu Fukabori,
Motoaki Hatori,
Yoshitaka Ono,
Hiroshi Matsui,
Kazuhiro Suzuki,
Hidetoshi Yamanaka,
Youko Shigawa,
Takashi Kanazawa, Chitose Ogawa
[show abstract]
[hide abstract]
ABSTRACT: A 8-year-old boy with acute lymphocytic leukemia (ALL) had received chemotherapy and a complete bone marrow remission was obtained. Then he underwent bone marrow transplantation. After 6 months, he suddenly got left flank-low abdominal pain. Sequentially, he had swelling and redness of left scrotum, left testicular swelling and tenderness. Incision was done and enlarged and hard testis was diagnosed as testicular tumor, left orchiectomy was performed. Histological diagnosis was involvement of ALL, so he received radiotherapy. He remains free of disease by the present after 7 months.
Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 08/2004; 95(5):722-4.
