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•HLA-DRB1 epitope mismatch (EM) in the graft-versus-host direction in cord blood transplantation (CBT) is associated with lower relapse risk and better survival in patients in complete/partial remission, whereas HLA class I EM is not.•These associations also were observed even within HLA-DRB1 allele-mismatched transplantations, indicating that HLA EM might have an impact on relapse risk independent of allele mismatch.•High HLA-DRB1 EM in the graft-versus-host direction in CBT is not associated with increased nonrelapse mortality.•High HLA-DRB1 EM may lead to potent graft-versus-tumor effects without increasing nonrelapse mortality.

Viral infection is one of the lethal adverse events after cord blood transplantation (CBT). Human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) ligand divergences can increase the risk of viral infection due to conflicting interactions between virus-infected cells and immune cells. However, the relationship between these disparities and the frequency of viral infection after CBT remains to be evaluated. Herein, we have conducted a retrospective multicenter study to assess the effect of HLA and KIR ligand mismatches on viral infections after CBT. The study included 429 patients, among which 126 viral infections occurred before day 100. Viral infection was significantly associated with poorer overall survival (OS; hazard ratio [HR] 1.74, p< 0.01). Patients harboring ≥3 mismatches in the HLA allele and inhibitory KIR ligand mismatches (HLA & KIR mismatches) had a significantly greater prevalence of viral infection (HR 1.66, p= 0.04). Thus, patients with HLA & KIR mismatches had poorer outcomes in terms of non-relapse mortality (HR 1.61, p= 0.05). Our study demonstrates the unfavorable impacts of HLA & KIR mismatches on viral infections and non-relapse mortality after CBT. Evaluating the viral infection risk and performance of an appropriate and early intervention in high-risk patients and optimizing the graft selection algorithm could improve the outcome of CBTs.

Graft-versus-host disease-free, relapse-free survival (GRFS) is a useful composite end point that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT within the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group of 17 transplantation centers in Japan. The primary end point was GRFS. A stacked ensemble of Cox Proportional Hazard (Cox-PH) regression and 7 machine-learning algorithms was applied to develop a prediction model. The median age for the patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other state-of-the-art competing risk models (ensemble model: 0.670; Cox-PH: 0.668; Random Survival Forest: 0.660; Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk group and 40.69% for the low-risk group (hazard ratio compared with the low-risk group: 2.127; 95% CI, 1.19-3.80). We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine-learning algorithms.

Background: The dimorphism at position -21 of exon 1 in HLA-B gives rise to leader peptides featuring either methionine (M) or threonine (T) as the second residue in the processed leader peptide (HLA-B leader). The cell surface abundance of HLA-E is positively correlated with the copy number of −21M HLA-B. In hematopoietic cell transplantation (HCT), the MM genotype in the recipients is associated with worse outcomes after HLA-matched and mismatched unrelated bone marrow and peripheral blood stem cell transplantation compared with TT (Kanaya M, et al. ASH Annual Meeting 2021, Petersdorf EW et al. Lancet Haematol. 2020 and Blood. 2020). Eurocord/EBMT study revealed HLA-B leader mismatch in HLA-B mismatched combination is associated with relapse and non-relapse mortality (NRM) risks after cord blood transplantation (CBT) (Petersdorf EW et al. Haematologica 2021). Notably, approximately 70% of patients in the literature administrated anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. The impacts of HLA-B leader dimorphism on the outcomes of CBT still needed to be elucidated more. Particularly, we were interested in the significance of HLA-B leaders in CBT without an ATG, then we conducted a retrospective study to elucidate it.

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I–II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P= 0.018] and CBT (HR = 0.48, P< 0.001), but not after MDT (HR = 0.80, P= 0.267) compared with patients without acute GVHD. Grade I–II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P= 0.060) and this positive effect was significant after CBT (HR = 0.39, P= 0.003). A negative impact of grade III–IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.

To report on a patient with multicentric Castleman's disease (MCD) who showed an orbital pseudotumor as an initial manifestation. A Japanese male patient, 65 years old, initially exhibited swelling of the left eyelid. Computed tomography and magnetic resonance imaging showed an infiltrating orbital mass around the left eye. The patient was treated several times with short courses of oral corticosteroids without significant response. Eight years after the first examination, he was referred to our neuroophthalmology clinic owing to persistent eyelid swelling. He exhibited an accelerated erythrosedimentation rate, polyclonal hypergammaglobulinemia, and multiple cervical and thoracic mediastinal lymphadenopathies. Histopathological examination revealed mixed-type MCD from a cervical lymph node and chronic inflammatory cell infiltration from eyelid swelling. Four months after his first visit, the patient's condition was complicated by fever, general fatigue, and hypoxemia. A cell marker study of the swollen lymph node showed monoclonality, indicating the development of non-Hodgkin's lymphoma. The clinical course in this case suggests that an inflammatory reaction in the orbital tissue was initially present, before MCD, and that non-Hodgkin's lymphoma subsequently developed. Jpn J Ophthalmol2005;49:505–508 © Japanese Ophthalmological Society 2005

Introduction: Unrelated cord blood (UCB) and haploidentical related donor transplantation using post-transplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a human leukocyte antigen (HLA)-matched donor. Although a previous phase III study showed better outcomes after bone marrow transplantation (BMT) using PTCy-haplo than those after double unit UCB, a donor selection algorithm including peripheral blood stem cell transplant (PBSCT) using PTCy-haplo or high-risk patients remains to be clarified. With the aim to assess the relative efficacies of UCB and PTCy-haplo transplant, we performed a multi-center retrospective analysis to compare the clinical outcomes in patients with hematologic malignancies.

Background: HLA-B leader encodes methionine (M) or threonine (T) at position 2 and gives rise to TT, MT, or MM genotype. HLA-B M leaders promote higher HLA-E expression than T leaders, enhancing T cell and natural killer (NK) cell recognition on HLA-E via NKG2A and NKG2C related to cytomegalovirus (CMV) recognition. The dimorphic HLA-B leader informs acute graft-versus-host disease (GVHD) risk in HLA 1 allele mismatched unrelated hematopoietic stem cell transplantation (HCT) (Petersdorf EW et al. Lancet Haematol. 2020 and Blood. 2020) and haploidentical HCT (Fuchs EJ et al. 62nd ASH Annual Meeting 2020). However, the impact of the HLA-B leader genotype in HLA-matched related/unrelated donor HCT from the viewpoints of CMV reactivation has not been elucidated fully yet. We performed this retrospective study to explore the significance of HLA-B leaders in HLA-matched related/unrelated HCT in the Japanese population.

Kanda: Amgen Astellas BioPharma: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Bristol-Myers Squibb Co: Honoraria; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; NextGeM Inc: Patents & Royalties; Novartis Pharma K.K.: Honoraria; Ono Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; TEIJIN PHARMA LIMITED.: Honoraria. Imada: Celgene Co., Ltd.: Honoraria; Bristol-Myers Squibb K.K.: Honoraria; Astellas Pharma Inc.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co. Ltd.: Honoraria; Takeda Pharmaceutical Co. Ltd.: Honoraria; Novartis Pharma K.K.: Honoraria. Kondo: Asahi Kasei Pharmaceutical: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Chugai Pharma: Honoraria; MSD Pharmaceutical: Honoraria; Sumitomo Dainippon Pharma: Honoraria. Takaori-Kondo: Bristol-Myers K.K.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Research Funding; Celgene: Research Funding.

Kanda: CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; NextGeM Inc: Patents & Royalties; Novartis Pharma K.K.: Honoraria; Ono Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; TEIJIN PHARMA LIMITED.: Honoraria; Bristol-Myers Squibb Co: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Amgen Astellas BioPharma: Honoraria. Ichinohe: Takeda Pharmaceutical Co.: Honoraria; Kyowa Kirin Co.: Honoraria, Research Funding; FUJIFILM Wako Chemicals.: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; CSL Behring: Honoraria, Research Funding; Taiho Pharmaceutical Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Honoraria, Research Funding; Ono Pharmaceutical Co.: Honoraria, Research Funding; Nippon Shinyaku Co: Research Funding; Takara Bio Inc.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Repertoire Genesis Inc.: Honoraria, Research Funding; Novartis Pharma K.K.: Honoraria; Celgene: Honoraria; Otsuka Pharmaceutical Co.: Research Funding; Eisai Co.: Honoraria, Research Funding; Chugai Pharmaceutical: Research Funding; Bristol-Myers Squibb: Honoraria; AbbVie Pharma: Research Funding; Astellas Pharma: Honoraria, Research Funding. Atsuta: Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; Meiji Seika Pharma Co, Ltd.: Honoraria; Astellas Pharma Inc.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria.

Graft-versus-host-disease-free, relapse-free survival (GRFS) is a useful composite endpoint that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS.This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT at the Kyoto Stem Cell Transplantation Group (KSCTG), a multi-institutional joint research group of 17 transplantation centers in Japan. The primary endpoint was GRFS. A stacked ensemble of Cox proportional hazard regression and seven machine learning algorithms was applied to develop a prediction model.The median age of patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other top-of-the-art competing risk models (ensemble model: 0.670, Cox-PH: 0.668, Random Survival Forest: 0.660, Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk and 40.69% for the low-risk group, respectively (hazard ratio [HR] compared to the low-risk group: 2.127; 95% CI: 1.19-3.80).We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine learning algorithms.

Kanda: MSD: Honoraria; Takeda: Honoraria; Bristol-Meyers Squib: Honoraria; Otsuka: Honoraria; Daiichi Sankyo Company: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Astellas: Honoraria; Chugai: Honoraria; Kyowa Hakko Kirin: Honoraria; JCR Pharmaceuticals: Honoraria; NextGeM Incorporation: Patents & Royalties: 2019-011392. Imada:Bristol-Meyer Squibb K.K.: Honoraria; Celgene K.K.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Nippon Shinyaku Co.,Ltd.: Honoraria; Takeda Pharmaceutical Co.,LTD.: Honoraria; Novartis Pharma K.K.: Honoraria; Astellas Pharma Inc.: Honoraria. Takaori-Kondo:Takeda: Research Funding; Ono: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria; Kyowa Kirin: Research Funding; Chugai: Research Funding; Janssen: Honoraria; Pfizer: Honoraria.

Background: GvHD-free, relapse-free survival (GRFS) is a useful composite endpoint that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to establish a predictive model of GRFS after allo-HSCT, using a machine learning algorithm within the Kyoto Stem Cell Transplantation Group (KSCTG), a multi-institutional joint research group of 17 transplantation centers in Japan.

Ichinohe: Janssen Pharmaceutical K.K.: Honoraria; Taiho Pharmaceutical Co.: Research Funding; Bristol-Myers Squibb: Honoraria; MSD: Research Funding; Ono Pharmaceutical Co.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; JCR Pharmaceuticals: Honoraria; Nippon Shinyaku Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Alexion Pharmaceuticals: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Co.: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Eisai Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Novartis.: Honoraria; Mundipharma: Honoraria; Astellas Pharma: Research Funding.

Induced pluripotent stem cells (iPSC) have the capacity to generate various tissues/organs, and clinical application in autologous settingsin humans has just begun. However, autologous transplantation is hampered by the high time and cost required for the individual production of iPSC. To solve these issues, allogeneic iPSC transplantation (allo-iPS-T) from iPSC banking has been proposed. A candidate for this is iPSC induced from individuals with a homozygous HLA haplotype (HLA-homo), on the basis that HLA-homo iPSC might not be rejected by HLA haplotype-matched patients. Concerns have been raised over whether allo-iPS-T from HLA-homo iPSC induces immunogenicity in clinical settings. Cord blood transplantation (CBT) might be a suitable model for evaluating these concerns, because HLA mismatch CBT from donors with less than two HLA loci mismatches is common, and carries a high engraftment failure rate, with a range of 10% to 20%. Further, cord blood cells are reported to be good source for the production of iPSC. Here, we report an analysis of allogeneic immunogenicity which focuses on engraftment of unrelated transplantation from HLA-homo cord blood.

Imada: Celgene: Honoraria; Bristol-Meyers Squibb: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Nippon Shinyaku: Honoraria; MSD: Honoraria; Chugai: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Shire Japan: Honoraria; Ono: Honoraria; Mundipharma: Honoraria. Takaori-Kondo:Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Janssen Pharmaceuticals: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria.

Background: Three drug combinations are the standard treatment for newly diagnosed multiple myeloma (NDMM). However, induction, consolidation, and maintenance therapy have not been standardized in Japan. Therefore, in this single arm Phase II study, we evaluated bortezomib-based induction, autologous stem cell transplantation (ASCT), bortezomib-based consolidation, and bortezomib maintenance in transplant eligible NDMM patients and assessed clinical outcomes as well as the minimal residual disease (MRD) status.

Introduction:Natural killer (NK) cells are important components of graft-versus-leukemia alloreactivity after allogeneic hematopoietic cell transplantation (HCT) for leukemia, due to the inhibitory killer-cell immunoglobulin-like receptors (KIRs). Only NK cells expressing inhibitory KIRs to self human leukocyte antigen (HLA) can become licensed and more responsive to activating stimuli. However, NK cells with inhibitory KIRs for non-self HLA are proposed to exhibit transient alloreactivity after early allogeneic HCT. The inhibitory KIR2DL group of receptors interacts with HLA-C, which comprises two mutually exclusive groups: HLA-C1 (Asn80) and HLA-C2 (Lys80). KIR2DL1 receptor, which shows the most powerful inhibitory effect and is very frequently expressed in the Japanese population, recognizes the HLA-C2 group. Therefore, we studied combinations of donor and recipient HLA-C groups in children with acute leukemia who underwent unrelated cord blood transplantation (CBT) to clarify the impact of KIR2DL1 mediated-NK alloreactivity on clinical outcomes.

Ozawa: Celgene Japan: Consultancy; Sumitomo Dainippon Pharma Co. Ltd: Research Funding; JCR Pharmaceutical Inc: Consultancy; Takara Bio Inc: Research Funding. Takaori-Kondo:Pfizer: Research Funding; Eisai: Research Funding; Takeda Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; Kyowa Kirin: Research Funding; Cognano: Research Funding; Toyama Chemical: Research Funding; Mochida Pharmaceutical: Research Funding; Shionogi: Research Funding; Alexion Pharmaceuticals: Research Funding; Chugai Pharmaceutical: Research Funding; Janssen Pharmaceuticals: Speakers Bureau; Merck Sharp and Dohme: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau.

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and a high propensity to transform into acute myeloid leukemia (AML). Although hematopoietic stem cell transplantation can cure some MDS patients, most patients are not eligible to undergo the treatment because of advanced age or comorbidities. In order to choose the optimal treatments, predicting prognosis is crucial. Chromosomal karyotype, bone marrow (BM) blast percentage, and cytopenia are well-known prognostic factors for MDS patients. These factors are incorporated into the international prognostic scoring system and its revised version (IPSS-R). However, the impact of morphological abnormalities has not been fully determined. Thus, to elucidate this, we examined the influence of the number of dysplastic lineages and the presence of increased ring sideroblasts (RS) on the survival of MDS patients whose BM blast percentages were <5%.

Paroxysmal nocturnal hemoglobinuria (PNH) often affects young adults, including women of childbearing age. Because PNH hemolysis increases the risk of complications such as thrombosis during pregnancy and the postpartum period, proper management should be provided for pregnant patients with PNH. Eculizumab, a C5 complement inhibitor, could be a therapeutic option for such patients.Japan PNH Study Group aimed to survey the current status of management of pregnant PNH patients and to propose a consensus recommendation for such a challenging situation in the treatment of PNH. Clinical data were collected from 10 pregnant PNH patients from 7 institutes and analyzed. We had consensus meetings 5 times since January 2012.Summary of patients' characteristics are shown in Table. Age of the patients at the time of conception ranged from 29 to 40 years old (median 30). Plasma levels of LDH at the baseline assessment were 200-2300 IU/L (median 1900). PNH clone sizes in granulocytes were 1.6-96.0% (median 81). Prophylactic anticoagulation with heparin was employed in all patients except one who showed little hemolysis due to a small size of PNH clone. Four patients received eculizumab during pregnancy with favorable efficacy. Complications including preeclampsia, hemolytic episodes and deep venous thrombosis were manageable. Newborn babies were all healthy. A negligible amount of eculizumab was detected in cord blood of three babies.Recently successful pregnancy outcomes have been reported in patients with PNH on eculizumab therapy during pregnancy, and we also experienced additional 4 cases. As eculizumab inhibits intravascular hemolysis itself, it can be expected to lower the risk of complications during pregnancy and postpartum period in women with PNH. Eculizumab is a hybrid of IgG4 and IgG2, and the latter is known to be less prone to cross the placenta. In fact eculizumab concentrations in the cord blood was much lower than therapeutic levels. Importance of anticoagulation therapy has been emphasized for the management of pregnancy with PNH. Theoretically, if intravascular hemolysis is completely inhibited by eculizumab, the risk of thromboembolic complication would become as low as that in non-PNH pregnancies. It is not clear whether the use of anticoagulant is mandatory for the pregnant patients who are receiving eculizumab, although the use of anticoagulant should not be hesitated.Eculizumab could be safely and effectively used in pregnant patients with PNH. Taking these findings into account, we propose the following protocol for the management of a pregnancy with PNH, as shown in Figure.The patients are classified into 4 categories based on eculizumab use and the history of venous thromboembolisms or anticoagulant use.Usuki: Alexion Pharmaceuticals: Speakers Bureau. Urabe:Alexion Pharmaceuticals: Speakers Bureau. Kawaguchi:Alexion Pharmaceuticals: Honoraria. Miura:Alexion Pharmaceuticals: Research Funding. Morita:Alexion Pharmaceuticals: Research Funding. Nishiwaki:Alexion Pharmaceuticals: Research Funding. Ninomiya:Alexion Pharmaceuticals: Honoraria. Gotoh:Alexion Pharmaceuticals: Honoraria. Shichishima:Alexion Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Nishimura:Alexion Pharma: Research Funding, Speakers Bureau. Kanakura:Alexion Pharmaceuticals: Research Funding, Speakers Bureau.

Paroxysmal nocturnal hemoglobinuria (PNH) often affects young adults, including women of childbearing age. Because PNH hemolysis increases the risk of complications such as thrombosis during pregnancy and the postpartum period, proper management should be provided for pregnant patients with PNH. Eculizumab, a C5 complement inhibitor, could be a therapeutic option for such patients.

Standard treatment for localized diffuse large B cell lymphoma (DLBCL) has been rather a short cycle of immunochemotherapy followed by involved field radiotherapy or prolonged cycles of immunochemotherapy. There is no convincing evidence in favor of either strategy. This retrospective analysis is an attempt to compare these treatment options.Patients were eligible if they had histologicaly newly diagnosed localized DLBCL by the Osaka Lymphoma Study Group (OLSG) central review panel and registered between 2003 and 2011, and received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) like immunochemotherapy with more than three consecutive courses as initial therapy. In this study, we defined a localized DLBCL as DLBCL with Ann Arbor stage I or non-bulky (<10cm) stage II. One hundred thirty-seven localized DLBCL patients were analyzed retrospectively. Of 137 patients, 83 had 6 to 8 cycles of R-CHOP like immunochemotherapy (Chemo group), and 28 had 3 to 4 cycles of R-CHOP like immunochemotherapy followed by radiotherapy (Chemo+RT group). In this study, the efficacy and tolerability of the 2 treatment groups, Chemo group and Chemo+RT group, in localized DLBCL patients were compared. Treatment outcomes were evaluated, overall survival (OS), progression free survival (PFS) and toxicity were compared according to each treatment option and risk factor.With a median follow-up time of 34 months, neither OS nor PFS differ between these treatment groups. The 3-year OS were 85.5% in Chemo group and 96.2% in Chemo+RT group, respectively (P=0.225). The 3-year PFS were 74.3% in Chemo group and 89.7% in Chemo+RT group, respectively (P=0.185). A multivariate Cox regression model showed that Chemo+RT group have a tendency to improve PFS [hazard ratio =0.33; 95% confidence interval 0.10–1.07; P =0.066] of localized DLBCL compared with Chemo group. Grade 3 to 4 neutropenia and neutopenic fever were more frequent in patients with Chemo group (P<0.01, P<0.01, respectively).For the treatment of localized DLBCL, although the difference between two treatment options was not significant in efficacy, short cycle of immunochemotherapy followed by radiation therapy seems to be superior to prolonged cycles of immunochemotherapy in terms of safety. Further studies are needed to define the optimal treatment option for localized DLBCL in the rituximab era.No relevant conflicts of interest to declare.

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