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A novel anti-cytomegalovirus (CMV) agent, letermovir (LMV), could reportedly improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients because of its high potential to prevent CMV reactivation. Therefore, 685 Japanese allo-HCT recipients, of whom ~80% had a high risk of CMV reactivation, were retrospectively analyzed to assess the impacts of prophylactic LMV on the incidence of clinically significant CMV (csCMV) infection as well as their transplant outcome. By comparing 114 patients who received LMV prophylaxis for a median 92 days to 571 patients without prophylaxis, we observed that prophylactic LMV could significantly (1) reduce the 180-day cumulative incidence of csCMV infection (44.7 vs. 72.4%, p

BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of gene expression very similar to that seen in ALL with BCR-ABL1 with poor prognosis. A 22-year-old female was diagnosed with common-B-cell-ALL positive for CD10, CD19, CD22, CD79a, CD34, HLA-DR, and TdT in January 2017, and achieved complete remission (CR) with induction therapy, followed by consolidation therapy and maintenance therapy. In March 2020, 6 months after the completion of maintenance therapy, she relapsed. Inotuzumab ozogamicin (IO) was administered, and on day 28, bone marrow evaluation showed a morphologic CR. She had an HLA-identical sibling, and transplantation in her 2nd CR was planned. Because her ALL had been identified as BCR-ABL1-like ALL with CCDC88C-PDGFRB fusion, she was treated with imatinib for 2 months accompanied by 2 intrathecal methotrexate therapies, and 1 course of l-asparaginase, vincristine, and prednisolone in an outpatient setting. MRD analysis revealed potent efficacy of 2 months imatinib therapy; IgH MRD decreased from 1 × 10−2 to 1 × 10−3, and CCDC88C-PDGFRB/104ABL from 37.3 to 0. It is earnestly desired that well-designed clinical trials of TKI in ABL class-mutant BCR-ABL1-like ALL be conducted in Japan.

Background Factor V (FV) deficiency is a monogenic inherited coagulation disorder considered to be an ideal indication for gene therapy. To investigate the possibility of therapeutic application of genome editing, we generated induced pluripotent stem cells (iPSCs) from a FV-deficient patient and repaired the mutation of factor V gene (F5) using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9). Methods The patient's peripheral blood mononuclear cells were reprogrammed for iPSCs. The targeting vector was designed with homology arms against F5 containing the corrected sequence. Cas9 ribonucleoprotein (RNP) complex and targeting vector were electroporated into iPSCs. Gene-edited iPSCs were differentiated into hepatocyte-like cells (HLCs). Results The mutation of F5 in patient-derived iPSCs was repaired by CRISPR/Cas9. In concentrated culture supernatants of patient-derived iPS-HLCs, neither FV antigen nor activity was detected, while in those of gene-corrected iPS-HLCs, FV antigen and specific activity were 67.0 ± 13.1 ng/mL and 173.2 ± 41.1 U/mg, respectively. Conclusions We successfully repaired the mutation of F5 using the CRISPR/Cas9 and confirmed the recovery of FV activity with gene-corrected iPS-HLCs. Gene-edited iPSCs are promising for elucidating the pathophysiology as well as for a modality of gene therapy.

We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 109/L (high risk) or

Understanding of the impact of stem cell donation on donors’ health-related quality of life (HRQOL) remains limited. A prospective observational study of eligible unrelated donors enrolled in the Japan Marrow Donor Program was conducted to compare HRQOL and adverse events (AEs) between peripheral blood stem cell (PBSC) and bone marrow (BM) donors. In total, 107 PBSC donors and 108 BM donors were enrolled. HRQOL scores for physical status were significantly lower in BM donors 1 week post-harvest (P

It remains unclear whether the HLA haplotype of unrelated cord blood (UCB) should be matched to that of the patient in single UCB transplantation. Thus, using data from a Japanese registry, we analyzed the effect of haplotype matching on outcomes. Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included (N = 1347). The effects of haplotype matching and high-frequency HLA haplotype on outcomes were analyzed. Median patient age was 55 years. The cumulative incidences of neutrophil engraftment among groups with 0, 1, and 2 HLA haplotype matches were 79%, 82%, and 88%, respectively (P = .008). In a multivariate analysis, the group with 0 haplotype matches was marginally associated with worse neutrophil engraftment (P = .087) and significantly associated with platelet engraftment (P = .044) compared with the group with 1 haplotype match. Two-haplotype matches were associated with a higher risk of relapse. In the group with 1 haplotype match, the top 3 shared haplotypes were "A*24:02-B*52:01-C*12:02-DRB1*15:02" (HP-P1), "A*33:03-B*44:03-C*14:03-DRB1*13:02" (HP-P2), and "A*24:02-B*07:02-C*07:02-DRB1*01:01" (HP-P3). The presence of HP-P2 but not HP-P1 or HP-P3 was associated with a decreased risk of grades II to IV acute graft-versus-host disease (hazard ratio, .56; P = .001) but an increased risk of relapse (hazard ratio, 1.35; P = .045). HLA haplotype matching might be considered to improve engraftment. Two-haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute graft-versus-host disease and relapse.

In the ALCYONE trial, daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) reduced the risk of disease progression or death by 50% versus bortezomib, melphalan, and prednisone (VMP) in patients with transplant-ineligible newly diagnosed multiple myeloma. Here, we report a subanalysis of East Asian patients from ALCYONE. After a median follow-up of 17.1 and 15.9 months for Japanese (n = 50) and Korean (n = 41) patients, respectively, median progression-free survival for D-VMP versus VMP was not reached (NR) versus 20.7 months in Japanese patients and NR versus 14.0 months in Korean patients. The overall response rate for D-VMP versus VMP was 96% versus 92% in Japanese patients and 91% versus 61% in Korean patients. Using next-generation sequencing, minimal residual disease negativity at 10−5 sensitivity for D-VMP versus VMP was 33% versus 8% among Japanese patients and 17% versus 0% among Korean patients. Rates of any grade and grade 3/4 pneumonia were consistent with the rates observed for the global safety population. Similar efficacy and safety findings were observed in the combined Japanese and Korean subgroup and ≥ 75 years of age subgroup. In conclusion, D-VMP was safe and efficacious in East Asian patients, consistent with the global ALCYONE population. Electronic supplementary material The online version of this article (10.1007/s00277-019-03794-9) contains supplementary material, which is available to authorized users.

The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300–400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidation therapy with nilotinib; 90 patients maintained MR4.5 with consolidation therapy, and 87 proceeded to discontinuation of nilotinib. The treatment-free remission (TFR) (MR4.5) rate at both 1 and 3 years after discontinuation of nilotinib was the same, at 60.9% (90% CI 51.6–69.7). Among 34 patients with molecular relapse, nilotinib was resumed in 33 patients; all of them attained MR4.5. There was no significant association between molecular relapse and age, sex, Sokal score, previous interferon-α exposure, duration of tyrosine kinase inhibitors treatment, or trough concentration of nilotinib. With nilotinib, it might be possible to avoid prognostic factors for TFR that exist with imatinib discontinuation. Cessation of nilotinib after two years of consolidation was safe and feasible. Trial registration UMIN000007141.

Objective We investigated whether minimal residual disease (MRD) status in adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is useful for decision on clinical indications for allogeneic hematopoietic stem cell transplantation (HSCT). Methods We prospectively monitored MRD after induction and consolidation therapy in adult patients with Ph-negative ALL. Results Among 103 adult ALL patients enrolled, 59 were Ph-negative, and MRD status was assessed in 51 patients. The probability of 3-year overall survival (OS) and disease-free survival (DFS) was 69% (95%CI 54-80) and 50% (95%CI 36-63), respectively. Patients who were MRD-negative after induction therapy (n = 15) had a significantly better 3-year DFS compared with those who were MRD-positive (n = 30; 73% vs 41%, P = 0.018). Patients who were MRD-positive after induction but became MRD-negative after consolidation chemotherapy C in the first course (n = 11) showed a significantly worse 3-year DFS compared with patients who were MRD-negative after induction chemotherapy A in the first course (45% vs 73%, P = 0.025). Conclusions These results indicate that DFS of about 70% can be expected in MRD-negative patients after induction therapy, and the patients did not benefit from HSCT in 1CR. This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000001519.

Allogeneic hematopoietic cell transplantation (allo-HSCT) is considered the curative treatment option in patients with aggressive adult T cell leukemia/lymphoma (ATLL), but the treatment of relapse after allo-HSCT remains a major challenge. We report a case of ATLL that was treated with sequential mogamulizumab (MOG) and lenalidomide (LEN) for early relapse after allo-HSCT. A 73-year-old Japanese male with acute-type ATLL underwent haploidentical-HSCT with post-transplant cyclophosphamide. He attained a complete response. However, ATLL relapse was diagnosed by biopsy of skin lesions that appeared on day 67. Discontinuation of immunosuppressant therapy alone did not result in improvement of ATLL, however, the skin lesions disappeared after an immune response was induced by sequential MOG and LEN. Following MOG and LEN, very serious toxic epidermal necrolysis (TEN) developed requiring high-dose intravenous immunoglobulin and methylprednisolone pulse therapy. Although graft-versus-host disease exacerbated and progressed to TEN, a complete response was achieved after successful treatment of TEN. These agents may thus enhance anti-ATLL activity by immune modulation. Further investigation is necessary to determine the optimal use of MOG and LEN in relapsed ATLL after allo-HSCT.

The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma.

Background The effectiveness of autologous haematopoietic stem cell transplantation (auto-HSCT) in treating severe systemic sclerosis (SSc) is established; however, the necessity of purified CD34+ cell grafts and the appropriate conditioning regimen remain unclear. This study aimed to compare the efficacy and safety of CD34-selected auto-HSCT with unmanipulated auto-HSCT to treat severe SSc. Methods This study was a post hoc analysis of a phase I/II clinical trial conducted in Japan. Nineteen patients with severe SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilised with cyclophosphamide (4 g/m2) and filgrastim (10 μg/kg/day). Following PBSC collection by apheresis, CD34+ cells were immunologically selected in 11 patients. All patients were treated with high-dose cyclophosphamide (200 mg/kg) monotherapy as a conditioning regimen and received CD34-selected (n = 11) or unmanipulated auto-HSCT (n = 8). Changes in skin sclerosis and pulmonary function were assessed over an 8-year follow-up period. Differences in the changes, toxicity, progression-free survival (PFS) and overall survival were compared between patients who had received CD34-selected auto-HSCT and those who had received unmanipulated auto-HSCT. Results Skin sclerosis progressively improved after transplantation over an 8-year follow-up period in both groups, and the improvement was significantly greater in the CD34-selected group than in the unmanipulated group. Forced vital capacity in the CD34-selected group continuously increased over 8 years, whereas in the unmanipulated group it returned to baseline 3 years after transplantation. Toxicity and viral infections, such as cytomegalovirus infection and herpes zoster, were more frequently found in the CD34-selected group than in the unmanipulated group. The frequency of severe adverse events, such as bacterial infections or organ toxicity, was similar between the two groups. No treatment-related deaths occurred in either treatment group. PFS of the CD34-selected group was greater than that of the unmanipulated group, and the 5-year PFS rates of the CD34-selected and unmanipulated group were 81.8% and 50% respectively. Conclusions CD34-selected auto-HSCT may produce favourable effects on improvement of skin sclerosis and pulmonary function compared with unmanipulated auto-HSCT. Use of CD34-selected auto-HSCT with high-dose cyclophosphamide monotherapy as a conditioning regimen may offer an excellent benefit-to-risk balance. Electronic supplementary material The online version of this article (10.1186/s13075-019-1823-0) contains supplementary material, which is available to authorized users.

Aggressive adult T-cell leukemia/lymphoma (ATL) is a hematological malignancy that is difficult to treat with chemotherapy alone, and allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy. We conducted a multicenter, prospective, observational study to clarify the treatment outcomes of aggressive ATL in the current era. Between 2015 and 2018, 113 patients aged 70 years or younger with newly diagnosed aggressive ATL were enrolled. The median age at diagnosis was 61 years. Treatment outcomes were compared with those of 1792 ATL patients diagnosed between 2000 and 2013 in our previous retrospective study. The inclusion criteria were the same in both studies. The prospective cohort demonstrated better overall survival (OS) than the retrospective cohort (2-year OS, 45% vs 29%, respectively; P < .001), with a much higher proportion of patients receiving allo-HCT (80% vs 34%, respectively; P < .001) and a shorter interval from diagnosis to allo-HCT (median, 128 vs 170 days, respectively; P < .001). Among the 90 patients who received allo-HCT (cord blood, n = 30; HLA-haploidentical related donors, n = 20; other related donors, n = 14; other unrelated donors, n = 26), the 2-year probabilities of OS, non-relapse mortality (NRM), and disease progression were 44%, 23%, and 46%, respectively. OS and NRM did not differ statistically according to donor type. Our results suggest that increased application of allo-HCT improved the survival of patients with aggressive ATL. The use of cord blood or HLA-haploidentical donors may be feasible for aggressive ATL when HLA-matched related donors are unavailable. This study was registered at the UMIN Clinical Trials Registry as #000017672.

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disease affecting mainly extranodal sites such as the lung, central nervous system (CNS), skin, kidney, and liver. We report a case of low-grade LYG involving the CNS that was successfully treated with interferon alpha (IFNα). A 69-year-old woman developed necrotic erythema of the skin and was initially diagnosed with pyoderma gangrenosum based on skin biopsy. She showed a limited response to prednisolone. Approximately 6 months after the initial onset, low-grade LYG was diagnosed after detection of CNS lesions on brain biopsy. The whole blood EBV-DNA load determined by real-time polymerase chain reaction was slightly elevated. Two months into IFNα therapy, skin and CNS lesions had responded favorably and the EBV-DNA load decreased. IFNα plays an important role in treatment of LYG through its antiproliferative, immunomodulatory, and anti-EBV effects. To our knowledge, this is the first case report of successful treatment with IFNα in Japan. Further investigation is necessary to determine optimal use of IFNα for LYG.

Acute lymphoblastic leukemia (ALL) is a common neoplasm in children, but less frequent in adults. Since information on clinical features and genetics of adult ALL in Japan is limited, we analyzed 215 subjects aged 16–65 years with untreated ALL enrolled in the Fukuoka Blood & Marrow Transplant Group studies ALL MRD 2002 and 2008. The prevalence of ALL was bimodal, with the larger group aged 56–65 years. Immunophenotypic characterization showed B-lineage is more frequent than T-lineage ALL (78.6 vs 13.0%), with age-related differences. The proportion with BCR-ABL1 rearrangement increased progressively with age, up to 55.7% among subjects aged over 56–65 years. Rearrangements involving the KMT2A gene, ETV6-RUNX1, and TCF3-PBX1 were rare in this study cohort. The overall incidence of hyperdiploidy was only 1.7%, and there were no cases with hypodiploidy. Overall survival varied by age and cytogenetics. Older subjects and those with BCR-ABL1 tended to have inferior outcomes. In this epidemiological study of Japanese adult ALL, the majority of subjects had B-lineage ALL, the T-cell phenotype was most frequent in those aged 16–25, and BCR-ABL1 rearrangement was very common, with prevalence increasing with age. These types of adult ALL are potentially manageable with targeted therapies.

Retransplantation is the only curative treatment option for patients with acute lymphoblastic leukemia (ALL) that has relapsed after allogeneic hematopoietic cell transplantation (allo-HCT); however, data in this setting remain scant. Hence, this multicenter, retrospective study aims to determine outcome predictors after retransplantation in relapsed ALL. We examined 55 recipients who underwent multiple allo-HCTs during 2006–2018. The 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality rates were 35.9%, 29.1%, and 23.6%, respectively. We observed a trend of better outcome in Ph + ALL (n = 22) patients compared with non-Ph ALL (n = 33) patients; the 2-year PFS was 40.9% versus 21.2%, indicating a beneficial effect of more potent second- or third-generation tyrosine kinase inhibitors. Univariate analysis revealed that late relapse after the previous transplant was the only significant predictor of better transplant outcome among Ph + ALL patients, whereas factors related to prolonged OS/PFS in non-Ph ALL patients were late relapse after the previous transplant, longer duration from disease relapse/progression to second or more allo-HCT, disease status at the transplantation, and good performance status. Nevertheless, further investigations are warranted to determine whether novel molecular-targeted agents with higher efficacy and fewer toxicities could exceed conventional chemotherapies as a bridging strategy to next allo-HCT and improve the outcomes of non-Ph ALL patients.

We report a case of primary sclerosing cholangitis (PSC) with autoimmune hemolytic anemia (AIHA). A 47-year-old woman was diagnosed with PSC. One year later, she was admitted to our hospital for jaundice and fatigue. Magnetic resonance cholangiopancreatography (MRCP) showed worsening of the biliary stricture, and rapidly progressive anemia developed simultaneously. Based on the various laboratory findings, she was diagnosed with AIHA. The administration of prednisolone improved not only the anemia but also the biliary stricture. This case is impactful, as there are few case reports of PSC with AIHA. In addition, we were able to observe the changes in imaging findings using MRCP over time.

A previous dose‐finding study has suggested that romiplostim is effective in patients with refractory aplastic anaemia (AA) and 10 µg/kg once weekly was recommended as a starting dose. In this Phase II/III, multicentre, open‐label study, romiplostim was administered subcutaneously at a fixed dose of 10 µg/kg once weekly for 4 weeks (weeks 1–4) followed by weekly doses (5, 10, 15 and 20 µg/kg) titrated by platelet response for up to 52 weeks (weeks 5–52). A total of 31 patients with AA who were refractory to immunosuppressive therapy (IST) and thrombocytopenia (platelet count of ≤30 × 109/l) were enrolled. The primary efficacy endpoint of the proportion of patients achieving any haematological (platelet, neutrophil and erythrocyte) response at week 27 was 84% [95% confidence interval (CI) 66–95%]. Trilineage response was 39% (95% CI 22–58%) at week 53. The most common treatment‐related adverse events (AEs) were headache and muscle spasms (each 13%). All AEs were mild or moderate except for three patients with Grade 3 hepatic AEs; no AEs necessitated romiplostim discontinuation. Two patients developed cytogenetic abnormalities, of whom one returned to normal karyotype at last follow‐up. High‐dose romiplostim is effective and well tolerated in the treatment of patients with AA refractory to IST.

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)–negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus–encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy.

Supplemental Digital Content is available in the text., GNA13 is a G protein involved in modulating tumor proliferative capacity, infiltration, metastasis, and migration. Genomic alteration of GNA13 was frequently observed in follicular lymphoma (FL). In this study, we examined 167 cases of FL by immunostaining of GNA13 using tissue microarray to evaluate the clinical significance. There were 26 GNA13-positive cases (15.6%) and 141 GNA13-negative cases (84.4%). GNA13-positive cases had a higher incidence of early progression of disease for which disease progression was recognized within 2 years compared with GNA13-negative cases (P=0.03). There were no significant differences in other clinicopathologic factors including histological grade, BCL2-IGH translocation, immunohistochemical phenotype, and Follicular Lymphoma International Prognostic Index. In addition, overall survival and progression-free survival were poorer in GNA13-positive cases than in GNA13-negative cases (P=0.009 and 0.005, respectively). In multivariate analysis, GNA13 positivity was found to be a poor prognostic factor for overall survival and progression-free survival. Thus, GNA13 protein expression was an independent prognostic factor and may affect disease progression in FL.

Disease status at allogeneic hematopoietic cell transplantation (HCT) is an important pretransplant prognostic factor of HCT in adult T cell leukemia/lymphoma (ATL); however, other prognostic factors, including comorbidities, were not predictive in small cohort analyses. Several scoring systems (HCT-specific comorbidity index [HCT-CI]/modified European Group for Blood and Marrow Transplantation risk score [mEBMT]) have been adopted to predict HCT outcomes in other hematologic malignancies. We retrospectively evaluated HCT-CI and mEBMT to predict nonrelapse mortality (NRM) in 824 ATL patients registered in the Japan Society for Hematopoietic Cell Transplantation TRUMP database, from 2008 until 2013. A higher HCT-CI was associated with greater NRM when comparing HCT-CI 0 versus HCT-CI 1 to 3 and HCT-CI 0 versus HCT-CI ≥ 4. A higher mEBMT score was not associated with higher NRM when comparing mEBMT 0 to 3 with 4 to 6. Because ATL patients are older and consequently at risk of additional complications, we developed an optimized prognostic index for ATL (ATL-HCT-PI) using known risk factors: age, HCT-CI, and donor–recipient sex combination. The ATL-HCT-PI scores effectively predicted the 2-year NRM (22.0%, 27.7%, and 44.4%, respectively). Therefore, the newly developed ATL-HCT-PI, in combination with other risk factors, is more useful for predicting NRM in HCT for ATL patients.

// Joji Shimono 1, 9 , Hiroaki Miyoshi 1 , Takeharu Kato 2, 7 , Takeshi Sugio 3 , Kohta Miyawaki 3 , Tomohiko Kamimura 4 , Takuto Miyagishima 5 , Tetsuya Eto 6 , Yoshitaka Imaizumi 7 , Koji Kato 3 , Koji Nagafuji 8 , Koichi Akashi 3 , Masao Seto 1 , Takanori Teshima 9 and Koichi Ohshima 1 1 Department of Pathology, Kurume University, School of Medicine, Kurume, Japan 2 Department of Hematology, Sasebo City General Hospital, Sasebo, Japan 3 Department of Medicine and Biosystemic Science, Kyushu University Faculty of Medicine, Fukuoka, Japan 4 Department of Hematology, Hara Sanshin Hospital, Fukuoka, Japan 5 Department of Hematology, Kushiro Rosai Hospital, Kushiro, Japan 6 Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan 7 Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan 8 Department of Hematology, Kurume University, School of Medicine, Kurume, Japan 9 Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan Correspondence to: Hiroaki Miyoshi, email: miyoshi_hiroaki@med.kurume-u.ac.jp Keywords: follicular lymphoma; hepatitis C virus; poor prognosis; NS3; overall survival Received: July 23, 2017 Accepted: November 13, 2017 Published: December 11, 2017 ABSTRACT Hepatitis C virus (HCV) is a single-stranded RNA virus that not only affects hepatocytes, by B cells as well. It is thought that HCV is involved in the onset of B-cell lymphoma. The clinicopathological characteristics of HCV-positive diffuse large B-cell lymphoma (DLBCL) and HCV-positive splenic marginal zone lymphoma (SMZL) are known, but there has been no report on HCV-positive follicular lymphoma (FL). In this study, the clinicopathological characteristics of HCV-positive FL were examined in 263 patients with FL who were classified into a HCV-positive group with HCV antibody and negative groups without one. The number of patients with HCV-positive FL and HCV-negative FL was 10 (3.8%) and 253 (96.2%), respectively. The patients with HCV-positive FL commonly had more than one region of lymphadenopathy, Ann Arbor stage III/IV, hemoglobin

// Joji Shimono 1, 3 , Hiroaki Miyoshi 1 , Fumiko Arakawa 1 , Kensaku Sato 1 , Takuya Furuta 1 , Reiji Muto 1 , Eriko Yanagida 1 , Yuya Sasaki 1 , Daisuke Kurita 1 , Keisuke Kawamoto 1 , Koji Nagafuji 2 and Koichi Ohshima 1 1 Department of Pathology, Kurume University, School of Medicine, Kurume, Japan 2 Department of Hematology, Kurume University, School of Medicine, Kurume, Japan 3 Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan Correspondence to: Hiroaki Miyoshi, email: miyoshi_hiroaki@med.kurume-u.ac.jp Keywords: dendritic cell neoplasm; histiocytic sarcoma; survival; prognostic factor; BRAF Received: June 05, 2017 Accepted: September 21, 2017 Published: October 19, 2017 ABSTRACT Histiocytic and dendritic cell neoplasms are rare and poorly studied. We report the clinical characteristics and prognostic factors in such cases in Japan. We investigated the clinical characteristics and survival in 87 adult patients with histiocytic and dendritic cell neoplasms. Fifty patients had histiocytic sarcoma, 12 had Langerhans cell histiocytosis, 11 had follicular dendritic cell sarcoma, 8 had Langerhans cell sarcoma, 6 had interdigitating cell sarcoma and 1 had indeterminate dendritic cell sarcoma. The median follow-up period was 18.0 (range: 9.6-71.8) months, and median overall survival (OS) was 23.5 months . The 2-year OS rate was 49.2% . In the multivariate analysis, elevated lactate dehydrogenase (LDH) ( p =.004), ECOG performance status (PS) 2-4 ( p =.006), and Ann Arbor stage III-IV ( p =.008) affected OS. Stratification by elevated LDH, ECOG PS 2-4, and Ann Arbor stage III-IV allowed classification of patients into low risk, intermediate risk, and high risk groups. The same classification was applicable for HS and non-HS categories. In the rare neoplasms of histiocytic and dendritic cell sarcoma, ECOG PS, Ann Arbor stage, and LDH are important prognostic factors for predicting survival.

Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy. Extranodal invasion by FL generally involves the bone marrow, skin, and duodenum; splenic infiltration often occurs in the advanced stages. However, primary splenic FL is very rare. Hence, few studies have been performed on splenic FL, and its clinicopathological features have not been established. This study aimed to investigate the clinicopathological features of primary splenic FL, as compared to nodal FL. We analyzed 17 patients diagnosed with primary splenic FL and 153 control patients with systemic FL. Hepatitis C virus (HCV)-positive status was significantly more common in patients with splenic FL than in the control patients (p = 0.02). Ann Arbor stage III or IV (p = 0.0003) and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) (p = 0.03) were significantly less common in patients with splenic FL than in the control patients; however, the overall and progression-free survival curves were not significantly different between the groups. Among the 17 patients with splenic FL, the progression-free survival was significantly worse in patients who underwent splenectomy without receiving postoperative chemotherapy than in those who did (p = 0.03). These results suggest that primary splenic FL should be considered different from systemic FL; accordingly, its management should also be conducted differently.

Objectives T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. Methods We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. Results T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. Conclusion T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.

Summary Background Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. We aimed to ascertain the safety and activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) with high-dose methotrexate and intrathecal chemotherapy as CNS-oriented therapy for patients with previously untreated IVLBCL. Methods PRIMEUR-IVL is a multicentre, single-arm, phase 2 trial at 22 hospitals in Japan. Eligible patients had untreated histologically confirmed IVLBCL, were aged 20–79 years, had an Eastern Cooperative Group performance status of 0–3, and had no apparent CNS involvement at diagnosis. Patients received three cycles of R-CHOP (rituximab 375 mg/m2 intravenously on day 1 [except cycle one, which was on day 8]; cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2·0 mg] intravenously on day 1 of cycle one and day 2 of cycles two and three; and prednisolone 100 mg/day orally on days 1–5 of cycle one and days 2–6 of cycles two and three) followed by two cycles of rituximab with high-dose methotrexate (3·5 g/m2 intravenously on day 2 of cycles four and five) every 2 weeks and three additional cycles of R-CHOP. Intrathecal chemotherapy (methotrexate 15 mg, cytarabine 40 mg, and prednisolone 10 mg) was administered four times during the R-CHOP phase. The primary endpoint was 2-year progression-free survival. Efficacy analyses were done in all enrolled patients; safety analyses were done in all enrolled and treated patients. The trial is registered in the UMIN Clinical Trials Registry (UMIN000005707) and the Japan Registry of Clinical Trials (jRCTs041180165); the trial is ongoing for long-term follow-up. Findings Between June 16, 2011, and July 21, 2016, 38 patients were enrolled, of whom 37 were eligible; one patient was excluded because of a history of testicular lymphoma. Median follow-up was 3·9 years (IQR 2·5–5·5). 2-year progression-free survival was 76% (95% CI 58–87). The most frequent adverse events of grade 3–4 were neutropenia and leucocytopenia, which were reported in all 38 (100%) patients. Serious adverse events were hypokalaemia, febrile neutropenia with hypotension, hypertension, and intracerebral haemorrhage (reported in one [3%] patient each). No treatment-related deaths occurred during protocol treatment. Interpretation R-CHOP combined with rituximab and high-dose methotrexate plus intrathecal chemotherapy is a safe and active treatment for patients with IVLBCL without apparent CNS involvement at diagnosis, and this regimen warrants future investigation. Funding The Japan Agency for Medical Research and Development, the Center for Supporting Hematology-Oncology Trials, and the National Cancer Center.

Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs.

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.

Umbilical cord blood transplantation with a reduced-intensity conditioning regimen (RIC-UCBT) is used increasingly in patients who have comorbid organ functions and lack human leukocyte antigen-identical donors. We compared the outcomes in 35 patients who received mycophenolate mofetil plus cyclosporine (MMF/CSP, n = 17) or MMF plus tacrolimus (MMF/TAC, n = 18) for graft-versus-host disease (GVHD) prophylaxis after RIC-UCBT. Cumulative incidence of neutrophil engraftment was 94 and 89 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.34). The incidence of pre-engraftment immune reaction did not differ between the MMF/CSP (41 %) and MMF/TAC (39 %, p = 1.00) groups; however, patients in the MMF/TAC group tended to have a lower incidence of grade II-IV acute GVHD than those in MMF/CSP group (28 vs 53 %, p = 0.11). Overall survival (OS) at 1 year was 43 and 60 % in MMF/CSP and MMF/TAC groups, respectively (p = 0.39). Progression-free survival, non-relapse mortality, and relapse rate were comparable between the two groups (p = 0.76, 0.59, and 0.88, respectively). In multivariate analyses, MMF/TAC GVHD prophylaxis was closely associated with improved OS, but not with incidence of engraftment and acute GVHD. These results suggest that more intensive GVHD prophylaxis with MMF/TAC decreased acute GVHD without affecting other clinical outcomes, resulting in improved OS after RIC-UCBT.

The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow transplantation (BMT) is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BMT or peripheral blood stem cell transplantation from an HLA-matched sibling for leukemia were eligible. BMT was performed in 13% of the Caucasian patients and in 53% of the Japanese patients. On multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grade III or IV acute GVHD was significantly lower in the Japanese patients compared with the Caucasian patients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57 to 0.96), which resulted in lower risk of nonrelapse mortality in the Japanese patients (HR, 0.69; 95% CI, 0.54 to 0.89). The risk of relapse was also lower in this group. The lower risks of nonrelapse mortality and relapse resulted in lower overall mortality rates among the Japanese patients. In conclusion, our data indicate that irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, resulting in a lower risk of nonrelapse mortality.

A 72-year-old Japanese male was diagnosed as having monoclonal gammopathy of undetermined significance and was followed up without therapy. Three years later, the patient progressed to symptomatic multiple myeloma. Melphalan + prednisolone was administered as first-line chemotherapy for ~6 years. Since the patient was judged to exhibit refractory multiple myeloma, he subsequently received radiation therapy on the lumbar spine. The patient was enrolled in a clinical trial and received lenalidomide + lowdose dexamethasone (Rd) therapy. The patient achieved very good partial remission following four cycles of Rd. At this time, large granular lymphocytes (LGLs) increased to 25-40% of peripheral blood leukocytes, however, the LGLs were present in the blood (~8%) prior to lenalidomide treatment. By flow cytometry of surface antigens, it was revealed that the LGLs were positive for cluster of differnetiation (CD)2, 7, 8, 16, 56, and 57, and human leukocyte antigen-D related, however, were negative for CD3, 4 and 5, suggesting that these LGLs predominantly exhibited an natural killer (NK) cell phenotype. T-cell receptor β gene rearrangement was not detected by polymerase chain reaction. A (51)Cr release assay was performed to investigate whether the NK cells actually possessed activity. A low level of M protein was sustained for ~15 months. This implied the enhancement of immune activation during lenalidomide treatment. The present case study suggested that LGL cells induced by lenalidomide may contribute to long-term restraint of myeloma cells. This immune system component may contribute to disease control.

Inherited hemophagocytic lymphohistiocytosis (HLH) is a genetic anomaly disorder in which abnormally activated cytotoxic T lymphocytes cannot induce the apoptosis of target cells and antigen-presenting cells, leading to hemophagocytosis, pancytopenia, and a variety of symptoms such as a high fever. The present patient with adult-onset HLH developed refractory disease despite receiving immunosuppressive treatments. He underwent a reduced-intensity conditioning (RIC) regimen that comprised antithymocyte globulin (ATG) followed by cord blood transplantation (RIC-CBT). He achieved and maintained a complete donor type. The incorporation of ATG into RIC-CBT may prevent graft failure and control hemophagocytosis, however, further efforts are necessary to reduce infectious complications.

The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance. Sixty-four symptomatic patients aged between 20 and 65 years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1 year. Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41 months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group. The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.

We conducted two parallel prospective, multicenter, phase II studies to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) following myeloablative conditioning (MAC, n = 50) and reduced-intensity conditioning (RIC, n = 77). Event-free survival (EFS) at 1-year as for primary endpoint was 64% and 43% in the MAC and RIC groups, respectively. Neutrophil engraftment was achieved in 98% and 94% in the MAC and RIC groups, respectively. The incidences of grades II–IV and III–IV acute graft-versus-host disease (GVHD) were 18% and 8% in the MAC group, and 14% and 5% in the RIC group, respectively. Those of all grade and moderate to severe chronic GVHD at 2-year were 36% and 20% in the MAC group, and 27% and 20% in the RIC group, respectively. Overall survival (OS), EFS, nonrelapse mortality, and relapse rate at 2-year were 68%, 54%, 10%, and 36% in the MAC group, and 44%, 35%, 20%, and 45% in the RIC group, respectively. Notably, 83% and 86% of patients who survived without relapse stopped immunosuppressant at 2-year in the MAC and RIC groups, respectively. Our results indicate that both MAC and RIC are valid options for PTCy-haploPBSCT for adults with hematological malignancies.

We retrospectively analyzed the outcomes of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) who underwent first allogeneic stem cell transplantation (allo-SCT) at complete remission (CR) with myeloablative conditioning (MAC, n = 31) or reduced-intensity conditioning (RIC, n = 15) between 2001 and 2012. All the patients had received tyrosine kinase inhibitor (TKI)-based chemotherapy prior to allo-SCT. Overall survival (OS) rates (57 vs 63%, p = 0.53), leukemia-free survival rates (50 vs 65%, p = 0.29), and non-relapse mortality rates (39 vs 35%, p = 0.62) at 2 years were similar between the MAC and RIC groups. The minimal residual disease (MRD) status evaluated by sensitive polymerase chain reaction prior to allo-SCT did not influence the OS rate (77 vs 54%, p = 0.28) and leukemia-free survival rate (69 vs 51%, p = 0.48), irrespective of the conditioning intensity. Our data suggest that the RIC regimen may represent a sufficient intensity of therapeutic pre-transplant conditioning for patients with Ph+ALL who have maintained a hematological CR with TKI-combined chemotherapy.

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 104 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P

We prospectively compared outcomes of autologous stem cell transplantation (ASCT) versus high-dose cytarabine (HiDAC) consolidation as post-remission therapy for favorable- and intermediate-risk acute myelogenous leukemia (AML) in first complete remission (CR1). Two-hundred-forty patients under 65 years with AML-M1, M2, M4, or M5 subtypes were enrolled. After induction, 153 patients did not undergo randomization, while the remaining 87 who achieved CR1 were prospectively randomized to HiDAC (n = 45) or ASCT arm (n = 42). In the HiDAC arm, 43 patients completed three cycles of HiDAC, whereas in ASCT arm 22 patients completed two cycles of consolidation consisting of intermediate-dose cytarabine plus mitoxantrone or etoposide followed by ASCT. The three-year disease-free survival (DFS) rate was 41% in HiDAC and 55% in ASCT arm (p = 0.25). Three-year overall survival (OS) rates were 77 and 68% (p = 0.67). Incidence of relapse was 54 and 41% (p = 0.22). There was no significant difference in nonrelapse mortality between two arms (p = 0.88). Patients in the ASCT arm tended to have higher DFS rates and lower relapse rates than patients in HiDAC; however, there was no significant improvement in OS in patients with favorable- and intermediate-risk AML in CR1. Patients with AML are not benefited by the intensified chemotherapy represented by ASCT.

The Japan Marrow Donor Program (JMDP) has facilitated unrelated peripheral blood stem cell transplantation (URPBSCT) since 2010. We conducted a prospective multicenter observational study to evaluate the feasibility of such transplantation. Between 2011 and 2014, 51 patients underwent URPBSCT from 8/8 allele-matched donors for hematological malignancies. The median age of the patients was 50 years; 21 had high-risk disease. Myeloablative conditioning regimens were used in 31 patients, and tacrolimus based graft-versus-host disease (GVHD) prophylaxis was used for all patients. The cumulative rate of engraftment was 96%. With a median follow-up period of 610 days for survivors, 100-day and 1-year overall survival rates were 86 and 59%, respectively. The cumulative incidence of non-relapse mortality and relapse at 1 year were 14 and 35%, respectively. The incidence of grade II to IV acute GVHD at 100 days and extensive type of chronic GVHD at 1 year were 25 and 32%, respectively. The probability of overall survival was comparable with that of bone marrow transplantation from HLA matched-unrelated donors in Japan, although the incidence of chronic GVHD was higher. Further follow-up with more patients is clearly warranted to establish the optimal use of URPBSCT together with the approaches of minimizing chronic GVHD.