Introduction: Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy with very poor prognosis. We have initiated a all-case registration of ATL patients (Kagoshima ATL registry) to reveal the epidemiology, clinical profile and prognosis of ATL by constructing a database of ATL patients diagnosed in Kagoshima, Japan, one of the most pandemic areas for ATL in the world. Methods: We prospectively collected clinical information in newly diagnosed patients with ATL on or after April 1, 2021 at all facilities in Kagoshima Prefecture providing hematology services. The follow-up data in registered patients was then collected annually. This study was approved by the ethics committee of each institution. Results and Discussion; A total of 167 patients were registered during the period of April 1, 2021 to March 31, 2023, of which 161 patients were included in this analysis by excluding 3 patients who were not met the criteria of registration and 3 patients who had duplicated registration. The number of patients was 83, 52, 15, and 13 in acute, lymphoma, chronic, and smoldering types, respectively. In 161 cases, aggressive ATL (acute- and lymphoma-type, and chronic-type with unfavorable prognostic factors) and indolent ATL (smoldering-type and chronic-type without any unfavorable prognostic factors) was 143 cases, 18 cases, respectively. The median age of onset was 72 years old. The median observation period was 19.8 (0.6-35) months, and the median survival was 6.8, 11.6 months, not-reached, and not-reached for acute, lymphoma, chronic, and smoldering types, respectively. Survival stratification by the simplified ATL-prognostic index (sATL-PI) at diagnosis and the Japan Clinical Oncology Group (JCOG)-PI for acute and lymphoma-type ATL, and aggressive ATL were confirmed, respectively (P<0.0001). In aggressive ATL, 83.9 % (120/143) of patients received first-line treatment. Among them, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), VCAP-AMP-VECP (VCAP: vincristine, cyclophosphamide, doxorubicin, and prednisolone, AMP: doxorubicin, ranimustine, and prednisolone, and VECP: vindesine, etoposide, carboplatin, and prednisolone), any chemotherapy by cytotoxic agents combined with mogamulizumab (Moga+CTx), and CHP therapy combined with brentuximab vedotin (BV-CHP) were performed in 30.0 %, 28.3 %, 28.3 %, and 13.4% of patients, respectively. Allogeneic stem cell transplantation (Allo-HSCT) was performed in 11.2% (16/143) patients with aggressive ATL with a median age of 62.5 years (44-72 years). Allo-HSCT was performed in 25.9 % (15/58) of patients who were equal or younger than 70 years old at diagnosis. In 34 patients who received Moga+CTx and 16 patients who received BV-CHP in the first-line therapy, 94.1% and 68.7% of patients acquired CR or PR, respectively (P=0.073). The time to next treatment in patients who received Moga+CTx and BV-CHP were 8.1 and 3.2 months, respectively (P=0.0231), indicating that the remission by Moga+CTx was more durable than the BV-CHP in the first-line treatment. Second-line treatment was applied to 81 patients. BV or Moga with or without CTx were most frequently used in the second-line treatment (n=81). This registration is expected to provide real-world data of ATL by regional registry in one of the world's most endemic area in HTLV-1 under the circumstances of the decreasing of HTLV-1 infected individuals in younger people and recent introduction of novel therapeutic agents including tucidinostat and valemetostat in Japan.

A correction to this paper has been published: https://doi.org/10.1007/s12185-021-03125-7

Adult T-cell leukemia/lymphoma (ATLL), which is a peripheral T-cell lymphoma related to human T-lymphotropic virus type I (HTLV-1), is known as a poor prognostic disease and its median age of onset is late 60s. Allogeneic hematopoietic stem cell transplantation is considered a treatment modality to contribute prolonging the survival in some population of patients. Although cord blood transplantation (CBT) widely practiced for hematological malignancies, a Japanese registry data suggested that 1 yr and 2 yrs overall survival (OS) after CBT in ATLL patients was only about 30% and 20%, respectively (Kato K, et al. 2014 BBMT). On the other hand, promising results were reported in the patients who were received CBT during their disease was controlled (Fukushima T, et al. 2013 IJH). Since it would be considered that CBT with non-TBI regimens, especially using reduced intensity conditioning (RIC), have a potential of engraftment failure compared to TBI regimen, it is less common conditioning regimen for CBT. Here we report a safety and an efficacy of CBT with non-TBI-RIC regimen using fludarabine (Flu) and melphalan (Mel) in 34 ATLL patients. We analyzed days from the beginning of systemic chemotherapy to transplantation, engraftment of neutrophil (EN), overall survival (OS), incidence of GVHD, non-relapse mortality (NRM) and disease-mortality (DRM), respectively. OS was defined as survival days from transplantation. OS were analyzed with logrank test. Cumulative incidence of EN and GVHD was considered with early death and NRM was considered with DRM as a competing risk. Incidence of GVHD, EN, NRM, and DRM was analyzed with Gray's method. Statistical significance defined P<0.05. Statistical analysis was carried out using the EZR. Thirty-four patients (18 male, 16 female) were consecutively undergone CBT with non-TBI-RIC regimen using Flu 125 mg/m2 and Mel 140 mg/m2 between January, 2014 and August, 2018 at our institute where is located in HTLV-1-endemic area. Twenty-eight patients used tacrolimus 0.02 mg /kg/day (TAC) and methotrexate (MTX) 5 mg/m2 / day at day 1, 3, 6 after transplantation, 5 patients TAC and mycophenolate mofetil (MMF) 750-2000 mg/day and one patient TAC alone as a GVHD prophylaxis. Median age at CBT was 61 years (44-70) and 30 patients were diagnosed as acute type ATLL whereas 4 lymphoma type. Sixteen patients were status in CR and 18 non-CR at CBT. Median duration of observation was 839.5 days (370-1890) and median time to CBT from the beginning of systemic chemotherapy was 113 days (61-416). Cumulative incidence of EN was 91.2 % and median time to EN was 20 days (14-68). OS at 2 years after transplantation (2 yr OS) was 43.9 %. 2 yr OS in CR patients was 68.2 % whereas 22.2 % in non-CR. There is no statistical significance about OS in age, gender, and incidence of GVHD. Cumulative incidence of NRM at day 100 and DRM at 1 year after CBT was 26.5 % and 26.5 %, respectively. CBT with non-TBI-RIC regimen using Flu/Mel was safe based on the result of feasible incidence of EN and NRM after CBT. Since 43.9 % of 2 yr OS was relatively high rate compared to previous report of Japanese registry data, CBT with non-TBI-RIC regimen using Flu/Mel can be a promising treatment strategy for ATLL. Figure Disclosures Nakano: Novartis: Honoraria.

Adult T‐cell leukemia‐lymphoma (ATL) is a lymphoid malignancy caused by humanT‐cell leukemia virus type I. ATL is divided into four clinical subtypes (smoldering, chronic, lymphoma, and acute) according to Shimoyama's classification. Smoldering‐type ATL, recognized as indolent ATL, sometimes has been shown to transform to acute‐type ATL. An international consensus meeting recommended watchful waiting (carefully observed unless transformation occurs) or treatment with interferon‐alpha and zidovudine (IFN/AZT) for patients with smoldering‐type ATL. Determining the risk factors of transformation is important to help determine therapeutic strategies for smoldering‐ type ATL. Because ATL cells release a large amount of soluble interleukin‐2 receptor (sIL‐2R), the serum level of sIL‐2R in ATL patients reflects disease activity and tumor burden better than lactate dehydrogenase (LDH). In the latest retrospective nationwide survey, Katsuya et al found that sIL‐2R was a probable independent prognostic factor for indolent ATL. However, even the patients with smoldering‐type ATL whose levels of sIL‐2R are slightly increased (sIL‐2R ≤ 1000 U/

Enhancer of zests homologous (EZH)1 and its close homolog EZH2 are component of polycomb repressive complex (PRC) 2 protein complex, and play redundant and crucial role for the maintenance of transcriptional repression by tri-methylating histone H3 lysine 27 (H3K27). Hyper tri-methylation of H3K27 has been associated with lymphoma and myeloma progression, suggesting that PRC2 is a therapeutic target for hematological malignancies. Selective EZH2 inhibitors induce compensatory activation of EZH1 which in turn re-activates PRC2 function. We hypothesized that dual inhibition of EZH1 and EZH2 is more effective than selective EZH2 inhibition as anti-tumor therapy.

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status >= 2, hematopoietic cell transplantation- specific comorbidity index (HCT-CI) score >= 3, European Group for Blood and Marrow Transplantation (EBMT) risk score >= 5, HSCT from an HLA-mismatched donor, serum soluble interleukin- 2 receptor (sIL-2R) level >= 10,000 U/mL, lymphocyte count >= 4000/mu L, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

Mogamulizumab is a humanized monoclonal antibody against CC chemokine receptor 4 that induced a clinical response in 50% of patients with relapsed adult T-cell leukaemia-lymphoma (ATL) in a phase II study (Ishida et al, 2012). It has been reported that mogamulizumab is more effective against tumour cells in peripheral blood (PB) than in the skin and lymph nodes (LNs), and it frequently induces cutaneous adverse reactions (CARs) (Ishida et al, 2012). In this report, we retrospectively analysed patients with relapsed or refractory ATL who were treated with mogamulizumab as salvage therapy with a particular emphasis on CAR at 4 institutes in Kagoshima (Southwestern Japan), which is one of the most endemic areas of human T-cell leukaemia virus type I in the world. This study was approved by the institutional review boards at each institute. We analysed 72 patients with ATL who had received mogamulizumab monotherapy between June 2012 and December 2014. Therapeutic results [objective response rate (ORR), defined as complete response (CR) and partial response rate], adverse events (AEs), and survival rates were investigated in this study. AEs, including CARs, were graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 3.0 (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf). Overall survival (OS) was defined as the time from the initiation of mogamulizumab therapy to death. Statistical analyses were performed using Stata software (StataCorp LP, College Station, TX, USA) and EZR (Kanda, 2013). The comparisons between mean values were performed using a Student's t-test. The association between the categorical variables was assessed by the chi-square test. OS was determined according to the Kaplan–Meier method and analysed by the log-rank test. Univariate and multivariate analyses of OS were performed using a Cox hazards regression model with stepwise selection, and the incidence of CARs was treated as a time-varying covariate. Statistical significance was defined as P < 0·05. Patient characteristics are shown in Table 1. Twenty-seven patients (37·5%) were aged 70 years or older. None of the patients were treated with antiviral therapy using zidovudine and interferon-α. The median number of mogamulizumab treatment cycles was 5 (range: 1–10 cycles). The ORR was 36·1%, including 17 cases of CR (23·6%), and ORRs according to the disease lesions were 74·5% (35 of 47), 31·5% (17 of 54) and 57·7% (15 of 26) for PB, LNs and skin, respectively. ORRs according to the Eastern Cooperative Oncology Group performance status (PS) at the initiation of mogamulizumab therapy were 43·6% and 27·3% for patients with PS 0 or 1 and PS 2–4, respectively. The median follow-up time from the initiation of mogamulizumab therapy for censored cases was 14·5 months (range: 5·2–36·2 months). Median OS and 1-year OS were 5·4 months [95% confidence interval (CI): 4·5–8·3 months] and 28·5%, respectively. Fifty-seven patients died [51 due to disease progression, 5 due to infection, and 1 due to graft versus host disease (GvHD) after allogeneic stem cell transplantation]. Infusion reactions (41·7%), neutropenia (26·4%) and cytomegalovirus antigenaemia (26·4%) were frequently observed AEs, and 22 patients (30·6%) experienced CARs; however, all cases were manageable. CARs developed following a median of 5 cycles (range: 2–10 cycles), and the median period between the initial treatment with mogamulizumab and the occurrence of CARs was 40·2 days (95% CI: 27·0–53·0 days). The severity of CAR was grade 1 in three patients, grade 2 in seven patients, grade 3 in nine patients and grade 4 in three patients (two patients eventually developed toxic epidermal necrolysis). As the patients who developed CARs received more cycles of mogamulizumab compared with those who did not (median 7 cycles vs. 4 cycles, P = 0·002), we analysed 46 patients who received more than 4 cycles of mogamulizumab. Of the remaining 26 patients, 20 patients and 6 patients discontinued due to disease progression and underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT), respectively. The best responses of patients with CARs were superior to those of patients without CARs (P = 0·001) (Table 1). In the patients who received more than 4 cycles of mogamulizumab and experienced CARs [n = 20, median duration between initial therapy with mogamulizumab and incidence of CAR = 43·8 days (95% CI: 29·0–63·0 days)], the ORR was high (75·0%) including 11 cases of CR. In these patients, the ORRs according to the disease lesions were 92·3% (12 of 13) for PB, 81·8% (9 of 11) for skin and 71·4% (11 of 14) for LNs. In the patients who received more than 4 cycles of mogamulizumab, the OS for the patients who developed CARs was significantly longer compared with those of the patients who did not experience CARs (median OS: 15·7 vs. 5·4 months, P < 0·001) (Fig 1). With regard to the multivariate analyses, poor PS and hypoalbuminaemia at the beginning of mogamulizumab therapy were significant adverse prognostic factors, and the development of CARs was a significantly favourable prognostic factor [hazard ratio: 0·21 (95% CI: 0·10–0·42), P < 0·001] (Table SI). It has been suggested that a reduction of regulatory T cells by mogamulizumab would induce CARs (Ishida et al, 2013; Yonekura et al, 2014), and that CARs were observed in patients who received several cycles of treatment with mogamulizumab. The development of grade I to II mild acute GvHD was significantly associated with superior OS compared with the absence of acute GvHD (Kanda et al, 2012). With regard to the immune response, the prognostic impact of CARs following mogamulizumab therapy is highly similar to that of GvHD after allo-HSCT. In conclusion, mogamulizumab monotherapy is indicated to be safe and effective for patients with relapsed or refractory ATL. In particular, this multicentre study demonstrated that the response to mogamulizumab and the survival in patients who developed CARs were significantly superior to those in patients without CAR, and the development of CAR as a result of treatment with mogamulizumab is a favourable sign in terms of efficacy. We would like to thank all the patients and their families, the nurses, clinical research coordinators, and medical experts who were involved in this study for their excellent cooperation. This study was supported in part by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development (AMED). M.T., K.Y., M.Y., K.I., and A.U. were involved in the conception and design of the study; M.T., K.Y., D.N., K.H., T.T. and M.Y. were responsible for acquisition of data; M.T., K.Y., M.Y., K.I. and A.U. analysed and interpreted the data; M.T., K.Y., N.N., M.Y., K.I., and A.U. wrote the manuscript; all authors reviewed the manuscript and approved the final version for submission. All authors declare no competing interests. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Introduction: Epigenetic regulators are an emerging new target class for cancer therapy. Enhancer of zeste homolog 1 (EZH1) and EZH2 are alternative subunits of polycomb repressive complex 2 (PRC2), and catalyze tri-methylation of the 27th lysine residue of histone H3 (H3K27). The tri-methylation of H3K27 (H3K27me3) plays an important role in the repression of genes associated with tumor suppression and cell differentiation. DS-3201b is a dual inhibitor of EZH1/2 with activity against hematological cancer cell lines that include acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), and adult T-cell leukemia-lymphoma (ATL). The first-in-human (FIH) study (NCT02732275) is on-going to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and potential anti-tumor activity in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), including ATL. This preliminary analysis was aimed to develop a population PK model, to explore the exposure-response (E-R) relationships for key safety and PD endpoints, and to find the optimal dose and schedule for DS-3201b. Methods: As of August 2, 2017, clinical data that include plasma levels of DS-3201a (a free form of DS-3201b) and platelet counts were collected from 15 patients with NHL who were participated in the FIH study. They received DS-3201b oral once-daily dosing ranging from 150 mg to 300 mg in 28-day cycles. Population PK analysis for DS-3201a in plasma was carried out and the potential influence of patient characteristics on the PK of DS-3201a was investigated in a covariate analysis. The PK/PD model for platelet counts was developed using a semi-mechanistic model which consists of compartments that imitate platelet proliferation, maturation, circulation, and a feedback on proliferation. Preliminary E-R analyses were also performed for PD biomarker. Results: A 2-compartment PK model with first order elimination and absorption lag-time best characterized the plasma concentration-time profile of DS-3201a. Serum albumin was a significant covariate for total clearance. In the FIH study, platelet counts decreased to a nadir during the first treatment cycle and it returned to baseline without drug interruption in most patients who received 150 mg or 200 mg doses, whereas all patients who received 300 mg required dose interruption. The PK/PD model with drug effect on platelet proliferation and feedback compartments aptly described the time-course of platelet counts. Model-based simulations showed that up-titration schedule based on each patient's platelet count after cycle 1 treatment could allow administration of higher DS-3201b doses to a subset of patients with low risk of grade ≥3 thrombocytopenia. The results of E-R relationship for the inhibition of H3K27me3 in surrogate tissues will also be presented. Conclusion: We developed preliminary population PK and E-R models for DS-3201b in patients with relapsed or refractory NHL. Model-based simulations suggested that up-titration approach can be effective for DS-3201b to ensure continuity of treatment benefit while minimizing dose-dependent thrombocytopenia. Disclosures Atsumi: Daiichi Sankyo Co., Ltd.: Employment. Yoshiba: DaiichiSankyo Co., Ltd: Employment. Maruyama: Dai-ichi Sankyo, Chugai, Kyowa Hakko Kirin, Ono, Celgene, Janssen, GSK, Eisai, Mundipharma, Takeda, AbbVie, MSD, Sanofi, Pfizer, Otsuka, Novartis, Solasia, Zenyaku: Research Funding; Chugai, Kyowa Hakko Kirin, Ono, Celgene, Janssen, Eisai, Mundipharma, Takeda: Honoraria. Tobinai: HUYA Bioscience: Honoraria; Janssen: Honoraria, Research Funding; AbbVie: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Servier: Research Funding; Daiichi Sankyo Co., Ltd: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Ishida: Kyowa Hakko Kirin Co., Ltd. Celgene K.K. Bayer Pharma AG: Honoraria, Research Funding. Ishitsuka: Celgene Kyowa Hakko Kirin Bristol-Myers Squibb Chugai Pharmaceutical Takeda Pharmaceutical mundiharma Taiho Daiichi Sankyo Janssen Novartis Pfizer Astellas sanofi Genzyme Alexion Sumitomo Dainippon Eisai Mochida Shire Otsuka Ono Teijin: Honoraria, Research Funding. Tsukasaki: Kyowa-Kirin: Honoraria; Chugai/Roche: Honoraria; DaiichiSankyo: Consultancy; Celgene: Honoraria, Research Funding; Mundypharma: Research Funding; Takeda: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria; HUYA: Honoraria. Adachi: Daiichi Sankyo Co., Ltd.: Employment. Fujitani: DaiichiSankyo: Employment. Tachibana: Daiichi Sankyo Co., Ltd: Employment. Yoshihara: Daiichi Sankyo Co., Ltd: Employment. Ishizuka: Daiichi Sankyo Co., Ltd: Employment.

Gender differences in physical function and muscle mass change in patients undergoing allogeneic hematopoietic stem cell transplantation

Background: Enhancer of zeste homolog 1 (EZH1) and EZH2 are alternative subunits of polycomb repressive complex 2 (PRC2), and catalyze tri-methylation of the 27th lysine residue of histone H3 (H3K27). This tri-methylated H3K27 (H3K27me3) is epigenetically important for downregulating genes associated with tumor suppression and cell differentiation. DS-3201b is a potent inhibitor with high specificity for EZH1 and EZH2 that has demonstrated anti-tumor activity against various hematological malignancies in preclinical studies (S. Fujita, et al. Blood 2015 126: 457) (D. Honma, et al. Cancer Sci. 2017). This Phase I study explored safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of DS-3201b in patients with relapsed or refractory non-Hodgkin lymphomas (NHLs), including adult T-cell leukemia-lymphoma (ATL) associated with human T-lymphotropic virus type I.

A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development.

Recovery of physical function and quality of life in patients undergoing hematopoietic stem cell transplantation: a 1-year follow-up

Allogeneic hematopoietic stem cell transplantation (HSCT) for advanced hematological diseases dose not reach a satisfactory result so far. Recently, umbilical cord blood transplantation (UCBT) is widely practiced for advanced hematological diseases by its tolerance of HLA matching. However, high incidence of transplant related complications such as engraftment failure, infections, pre-engraftment immune reaction (PIR) etc. are still issues to resolve. Although non-TBI regimens are easy to prepare, few reports investigated non-TBI regimens for UCBT. With respect to UCBT with non-TBI conditioning regimens, we examined efficacy and feasibility of them for high-risk hematological diseases.

An adult male patient was admitted to our hospital with systemic lymphadenopathy. He was diagnosed as having ALK-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Immunohistochemical staining revealed positive reaction for CD4, CD30, CD25, TIA-1, and Granzyme B, but negative for ALK and EBER. Although anti-HTLV-1 antibody in his serum was positive, monoclonal integration of HTLV-1 provirus DNA was not detected in his lymph node by Southern blot analysis. He was treated by combination chemotherapy, and complete remission was obtained by 8 courses of CHOP therapy. Subsequently he received autologous stem cell transplantation (auto-SCT). Fifteen months after auto-SCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis of abnormal lymphocytes revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of T-cell receptor b. The patient was therefore diagnosed as chronic type of adult T-cell leukemia-lymphoma (ATL), and immediately progressed to acute type with central nervous system involvement. He died of tumor progression regardless of intensive chemotherapy. We analyzed genomic alterations of the ALCL cells and the chronic type ATL cells using high-resolution array comparative hybridization. These results revealed that the genomic alteration pattern of ALCL was different from those of the chronic type. Chronic type ATL cells had the genetic alterations such as 1q gain and CD58 loss that were frequently observed in acute type ATL than the chronic type, suggesting that these genetic events might contribute to the transformation of this case. TCR rearrangement analyses using PCR were performed for the tumor cells of ALCL and ATL to evaluate the origin of these tumor cells. Results showed that tumor cell clone of the ATL might have already proliferated in ALCL lymph node. This finding suggests that lymph nodes can serve as a niche for ATL development.

Introduction: Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy, which is caused by human T-cell leukemia virus type I (HTLV-1) and is considered to be derived from regulatory T cells (Treg). ATL is usually resistant to conventional chemotherapies and the patients with ATL have very poor prognosis. Mogamulizumab (Moga) is a humanized monoclonal antibody against CC chemokine receptor 4 (CCR4) which is expressed on T-helper type 2, Treg and tumor cells from most patients with ATL. It was reported that Moga used to treat ATL with 50% efficacy in a phase II study and frequently developed cutaneous adverse reactions (CAR). In that study, development of CAR was reported to be closely associated with the response to Moga therapy. To confirm efficacy and safety of Moga therapy for ATL, we retrospectively analyzed relapsed or refractory ATL patients who were treated by Moga at 4 institutes in Kagoshima, one of the endemic areas of HTLV-1 infection, Southwestern Japan.