Jun Okamura

Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: A nationwide retrospective study

Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as a curative option for adult T-cell leukemia (ATL), an intractable mature T-cell neoplasm causally linked with human T-cell leukemia virus type I (HTLV-I). We compared outcomes of 386 patients with ATL who underwent allogeneic HSCT using different graft sources: 154 received human leukocyte antigen (HLA)-matched related marrow or peripheral blood; 43 received HLA-mismatched related marrow or peripheral blood; 99 received unrelated marrow; 90 received single unit unrelated cord blood. After a median follow-up of 41 months (range, 1.5-102), 3-year overall survival for entire cohort was 33% (95% confidence interval, 28%-38%). Multivariable analysis revealed 4 recipient factors significantly associated with lower survival rates: older age (> 50 years), male sex, status other than complete remission, and use of unrelated cord blood compared with use of HLA-matched related grafts. Treatment-related mortality rate was higher among patients given cord blood transplants; disease-associated mortality was higher among male recipients or those given transplants not in remission. Among patients who received related transplants, donor HTLV-I seropositivity adversely affected disease-associated mortality. In conclusion, allogeneic HSCT using currently available graft source is an effective treatment in selected patients with ATL, although greater effort is warranted to reduce treatment-related mortality.

Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study

Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL.

Social outcomes and quality of life of childhood cancer survivors in Japan: a cross-sectional study on marriage, education, employment and health-related QOL (SF-36).

Social outcomes and quality of life (QOL) of childhood cancer survivors (CCSs) remain unknown in Japan. We investigated these outcomes in young adult CCSs compared to those of their siblings in Japan, and analyzed the association between social outcome and SF-36 health survey subscale scores. Between 2007 and 2009, we performed a cross-sectional survey using self-rating questionnaires. We estimated social outcomes and health-related QOL by performing the SF-36 in each group: CCSs with or without stem cell transplantation (SCT)/radiotherapy (RT) and their siblings. Adjusted odds ratios for outcomes of interest were estimated using logistic regression analysis. Questionnaires from 185 CCSs and 72 CCS’s siblings were analyzed. There were no differences in educational attainment or annual income. The SF-36 subscale scores of CCSs with SCT and RT were significantly lower than those of siblings in physical functioning (PF) (p < 0.001 and 0.003, respectively) and general health (GH) (both p = 0.001). Lower PF scores correlated with recurrence (p = 0.041) and late effects (p = 0.010), and poor GH scores with late effects (p = 0.006). The CCSs had made efforts to attain educational/vocational goals; however, a significant proportion of CCSs who had experienced late effects remain at increased risk of experiencing diminished QOL.

Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy

To examine the late effects and health-related quality of life of childhood cancer survivors (CCS) after radiotherapy (RT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: CCS treated with or without RT, and a general population matched for age, gender, residential area, and work status. The numbers in each group were 113, 72, and 1,000, respectively. The median ages of CCS at diagnosis and the time of the survey were 8 and 22xa0years, respectively. The mean final heights of males and females were significantly lower in CCS with RT than in the other 2 groups. Risk factors for a short stature were total body irradiation (TBI) [odds ratio (OR) 17.8, pxa0<xa00.001], spinal irradiation (OR 8.31, pxa0=xa00.033), and an age younger than 10xa0years at diagnosis. Late effects were observed in 68% of CCS with RT compared with 36% of CCS without RT. Multivariate analysis revealed that TBI was significantly associated with endocrine dysfunction (OR 12.3), skull and spinal irradiation with cognitive dysfunction (OR 16.1 and 11.5, respectively), and spinal irradiation with a short stature (OR 14.1), respectively. Physical dysfunction, psychological stress, and problems of social adaptation were observed in >50% of CCS with RT.

TBI and melphalan followed by allogeneic hematopoietic SCT in children with advanced hematological malignancies

We evaluated the efficacy and safety of the conditioning regimen that consisted of TBI and melphalan (L-PAM), followed by hematopoietic SCT (HSCT) in 23 children with advanced hematological malignancies. The median age at HSCT was 9 (range, 2–15) years. The underlying diseases were ALL in 16 patients (5 in CR2, 3 in CR3, 6 in relapse (RP) and 2 in induction failure (IF)), AML in 4 patients (3 in RP and 1 in IF) and non-Hodgkins lymphoma in 3 patients (1 in CR3, 1 in CR4 and 1 in RP). The stem cell sources were BM for 19 patients and cord blood for 4 patients. All patients received the conditioning regimen that consisted of TBI 12 or 13.2u2009Gy and L-PAM 210u2009mg/m2. In all, 22 patients engrafted on the median of day 16 (range, 10–23). The regimen was well tolerated and common regimen-related toxicities (RRTs) included grade II stomatitis and grade I hepatic toxicity. The cumulative incidences of RP and TRM were 47.6 and 21.5%, respectively. At a median follow-up of 24.4 months, the probability of disease-free survival was 41.0%. The regimen may provide sufficient anti-leukemic effect without increased RRT for advanced pediatric hematological malignancies.

Can allo-SCT with RIC cure ATLL? Long-term survivors with excellent PS and with heterogenous HTLV-1 proviral load level

Objective We evaluated the safety and feasibility of allogeneic hematopoietic stem cell transplantation with RIC from matched sibling donors (MSD) for ATLL pts using a conditioning regimen consisting of fludarabine and busulfan. Low-dose antithymocyte globulin was added in the 1st study (NST-1), while it was omitted for the 2nd study (NST-2). We present the results of long-term follow-up of the two trials as well as the longitudinal patterns of changes in HTLV-1 proviral load in survivors.

Outcome of children with refractory anaemia with excess of blast (RAEB) and RAEB in Transformation (RAEB-T) in the Japanese MDS99 study

We report the outcome of 16 children with refractory anaemia with excess of blasts (RAEB; n = 4) and RAEB in transformation (RAEB‐T; n = 12) following induction therapy with etoposide, cytarabine and mitoxantrone (ECM) prior to haematopoietic stem cell transplantation (HSCT). The median observation period was 77 months (range 5–123). Complete remission rate was 81% following induction; no toxic deaths occurred. Eight‐year event‐free survival and overall survival was 50% and 56%, respectively. None of the three patients with a complex karyotype survived, suggesting karyotype is a crucial prognostic factor for survival. This study indicates the safety and high remission rate of ECM and high survival rates after HSCT for paediatric RAEB and RAEB‐T.

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group.

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (Pxa0=xa00.061). The mean age of 13.0xa0years at the diagnosis of leukemia in the HLHxa0+xa0ALL group was significantly higher than the 6.05xa0years observed in the remaining ALL groups (Pxa0=xa00.001). A female predisposition was noted, as all four patients were female (Pxa0=xa00.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (Pxa0=xa00.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

The second therapeutic trial for children with hematological malignancies who relapsed after their first allogeneic SCT: long-term outcomes.

Nishikawa T, Inagaki J, Nagatoshi Y, Fukano R, Nakashima K, Ito N, Sawa D, Kawano Y, Okamura J. The second therapeutic trial for children with hematological malignancies who relapsed after their first allogeneic SCT: Long‐term outcomes.

Successful treatment with plasma exchange for disseminated cidofovir-resistant adenovirus disease in a pediatric SCT recipient

Successful treatment with plasma exchange for disseminated cidofovir-resistant adenovirus disease in a pediatric SCT recipient