工藤 寿子

BACKGROUND:The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan.;METHODS:A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative

:The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG

We analyzed 3 hematopoietic stem cell transplant (HSCT) recipients with inherited chromosomally integrated human herpesvirus-6 (inherited CIHHV-6). Cases 1 (inherited CIHHV-6A) and 2 (inherited CIHHV-6B) were inherited CIHHV-6 recipients. Case 3 received bone marrow from a donor with inherited CIHHV-6B. Following HSCT, HHV-6B was isolated from Case 1. HHV-6A and -6B messenger RNAs were detected in Cases 1 and 3.

Incorporation of imatinib into chemotherapeutic regimens has improved the prognosis of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). We investigated a role of imatinib immediately before hematopoietic stem cell transplantation (HSCT). Children with Ph+ALL were enrolled on JPLSG Ph+ALL 04 Study within 1 week of initiation of treatment for ALL. Treatment regimen consisted of Induction phase, Consolidation phase, Reinduction phase, 2 weeks of imatinib monotherapy phase, and HSCT phase (Etoposide+CY+TBI conditioning). Minimal residual disease (MRD), the amount of BCR–ABL transcripts, was measured with the real-time PCR method. The study was registered in UMIN-CTR: UMIN ID C000000290. Forty-two patients were registered and 36 patients (86%) achieved complete remission (CR). Eight of 17 patients (47%) who had detectable MRD at the beginning of imatinib monotherapy phase showed disappearance or decrease in MRD after imatinib treatment. Consequently, 26 patients received HSCT in the first CR and all the patients had engraftment and no patients died because of complications of HSCT. The 4-year event-free survival rates and overall survival rates among all the 42 patients were 54.1 ± 7.8% and 78.1 ± 6.5%, respectively. Four of six patients who did achieve CR and three of six who relapsed before HSCT were salvaged with imatinib-containing chemotherapy and subsequently treated with HSCT. The survival rate was excellent in this study although all patients received HSCT. A longer use of imatinib concurrently with chemotherapy should eliminate HSCT in a subset of patients with a rapid clearance of the disease.

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.

Despite several advances in the treatment of Epstein-Barr virus (EBV) in recent years, patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) do not always show satisfactory outcomes. We here conducted a nationwide survey in Japan to identify prognostic factors of EBV-HLH in children with this disease in an effort to improve the management and the outcomes of these patients.<br /> Between January 2003 and June 2008, we enrolled 98 children younger than 18 years of age who were diagnosed with EBV-HLH. We then studied the clinical characteristics and laboratory findings at the time of diagnosis with the aim to identify prognostic factors for EBV-HLH.<br /> The mean age of onset of EBV-HLH was 3.9 ± 2.8 years. Most of our patients presented with fever, hepatosplenomegaly, lymphadenopathy, and hemophagocytosis of bone marrow. Sixty-two percent of patients showed T cell clonality, and 97% had EBV infection in either T or natural killer cells. Most patients (60%) were treated with a multi-agent chemotherapeutic regimen, including corticosteroid, etoposide, and cyclosporine. After initial treatment, 90.3% of patients were in remission, and 7 patients (8.2%) experien

症例は9 か月男児。生後1 か月時に乳児急性リンパ性白血病と診断され寛解導入療法施行後，6 か月時に非血縁間臍帯血移植を施行。急性GVHD は軽快しシクロスポリン（CsA）を漸減，慢性GVHD 所見は認めず移植後101日目に退院。9 か月時（移植後115 日目），ネフローゼ症候群を来しステロイド内服を開始。しかし改善せず，ステロイド抵抗性ネフローゼ症候群と診断しステロイドパルス療法を3 クール施行し1 歳時（移植後6 カ月）に腎生検を施行。微小変化型と考え，CsA 増量と，ミゾリビン（MZR）を追加したうえでステロイドパルス療法を2 クール施行するが尿蛋白は陰性化を認めなかった。免疫抑制剤を多剤併用しており原疾患の再発も危惧されたが，原疾患がB 細胞性急性リンパ性白血病であったこともありリツキシマブ（RTX）を4 回投与したところ，尿蛋白陰性化し1 歳3 か月時に退院。その後は寛解を維持している。臍帯血移植後ネフローゼ症候群という稀な疾患を経験したため報告する。

造血幹細胞移植時の粘膜障害による疼痛に対して、フェンタニルを用いたPCAが使用された14例の小児を対象に後方視的研究を行った。PCA開始時のベース量とボーラス量は過去の報告より少なくロックアウトタイムは長く設定されていた。10例で疼痛が軽減して中止されたが、2例では効果が不十分のためモルヒネに変更された。有害事象として3例に眠気が認められた。今後は有用性の評価のために前方視的研究を行う必要がある。(著者抄録)