Post-transplant relapse remains a major cause of treatment failure in adult B-cell acute lymphoblastic leukemia (ALL). The introduction of inotuzumab ozogamicin (InO) and blinatumomab (Blina) has expanded salvage options; however, their impact on outcomes and safety in patients relapsing after allogeneic stem cell transplantation has not been fully defined. To evaluate the impact of the availability of InO and Blina on clinical outcomes in adult B-cell ALL patients with post-transplant relapse, and to assess the safety of these agents in the post-transplant setting. We retrospectively analyzed 150 adult patients with B-cell ALL who relapsed after the first allogeneic stem cell transplantation. Patients were divided according to the time of their post-transplant relapse based on the approvals of InO and Blina in Japan: the pre-InO/Blina group (n = 95) and the post-InO/Blina group (n = 55). Outcomes were analyzed separately for Philadelphia chromosome (Ph)-negative and Ph-positive ALL. Overall survival (OS) after post-transplant relapse, complete remission (CR) rates as the best response before a second transplantation or last follow-up, and outcomes after a second transplantation were compared between groups. Adverse events associated with post-transplant use of InO and Blina were also evaluated. Among 95 patients with Ph-negative ALL, outcomes were significantly better in the post-InO/Blina group than in the pre-InO/Blina group, with the 2-year OS after post-transplant relapse improving from 19% to 51% (P = .003) and, among 88 treated patients, the CR rate increasing from 36% to 77% (P < .001). Multivariable analyses identified the time of post-transplant relapse and disease status at the first transplantation as independent prognostic factors for OS. Among 43 patients who underwent a second transplantation, the 2-year OS after second transplantation improved from 27% in the pre-InO/Blina group to 55% in the post-InO/Blina group (P = .029). In contrast, among 55 patients with Ph-positive ALL, OS after post-transplant relapse did not differ between groups. Among 32 patients treated with InO after post-transplant relapse, no patient developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) during InO therapy; however, 5 of 17 patients (29%) who subsequently underwent the second transplantation developed VOD/SOS. An interval of <2.5 months between InO and the second transplantation was associated with a higher VOD/SOS risk (56% versus 0%, P = .029). Among 30 patients treated with Blina, cytokine release syndrome occurred in 53% (grade 3 to 4, 7%) and immune effector cell-associated neurotoxicity syndrome in 13% (grade 3, 3%), with no fatal events. The prognosis of adult Ph-negative B-cell ALL after post-transplant relapse improved substantially in the post-InO/Blina era, including improved survival after a second transplantation. Overall, the safety profiles of InO and Blina in the post-transplant setting were acceptable, although VOD/SOS remains an important concern in patients proceeding to a second transplantation after InO.

Epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, has shown substantial activity in relapsed or refractory (R/R) B-cell lymphomas, but the immunological correlates of durable remission and treatment discontinuation remain unclear. We retrospectively analyzed 21 consecutive patients who initiated epcoritamab at our institution between 1 December 2023 and 31 December 2025, including 17 with R/R large B-cell lymphoma (LBCL) and 4 with R/R follicular lymphoma (FL). Clinical follow-up was updated through 18 May 2026. Serial cytotoxic T lymphocyte (CTL) subset and T-cell receptor (TCR) Vβ repertoire analyses were performed in selected cases. Among response-evaluable patients, the overall response rate was 9/14 in LBCL and 4/4 in FL. Median overall survival was 431 days in LBCL and 431.5 days in FL. Progression-free survival was analyzed descriptively because of the small sample size and substantial censoring. A patient with clinically and radiologically suspected central nervous system relapse of LBCL achieved radiological complete remission after epcoritamab treatment. In two LBCL and one FL case in whom epcoritamab was electively discontinued after complete remission, Vβ-skewed CTL populations were observed, and total memory CTLs exceeded total effector CTLs at discontinuation. These exploratory findings suggest that epcoritamab treatment may be associated with longitudinal remodeling of CTL subsets and Vβ-skewed CTL populations in selected responders. The potential relevance of these immunological patterns to durable response and treatment discontinuation should be validated in larger prospective cohorts with functional and sequence-based T-cell analyses.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive HTLV-1-associated T-cell neoplasm, and durable control of relapsed/refractory disease remains difficult without allogeneic hematopoietic stem cell transplantation. Mogamulizumab, an afucosylated anti-C-C chemokine receptor type 4 (CCR4) monoclonal antibody, and tucidinostat, an oral histone deacetylase inhibitor, have activity in this setting, but the immunovirological consequences of sequential CCR4-directed therapy and epigenetic modulation are unclear. We describe two patients with relapsed or refractory ATLL who achieved prolonged disease control after mogamulizumab/tucidinostat-based sequential therapy and underwent longitudinal monitoring of Tax301–309-specific CD8+ T cells, CD4/CD8 dynamics, HTLV-1 proviral DNA, and T-cell receptor (TCR) Vβ repertoire. Patient 1 had lymphoma-type ATLL with metabolic partial response after mogamulizumab plus EPOCH; tucidinostat was initiated 63 days after the final mogamulizumab dose. Tax301–309-specific CD8+ T cells increased from 0.03% at tucidinostat initiation to >0.8% during long-term follow-up, and disease control persisted for 32 months after tucidinostat initiation. Patient 2 had multiply relapsed ATLL and received four cycles of sequential mogamulizumab/tucidinostat, followed by rapid disappearance of circulating ATLL cells, normalization of soluble interleukin-2 receptor, and marked reduction of HTLV-1 proviral load from 565.7 copies/1,000 peripheral blood mononuclear cells to low levels. Disease control persisted for 17 months after treatment discontinuation. In both patients, TCR Vβ repertoire analysis showed memory CD8+ T-cell-predominant patterns, including expansion of a Vβ2 memory CD8+ T-cell population. These observations are hypothesis-generating and suggest that sequential tumor debulking, CCR4/Treg-axis modulation, and epigenetic treatment may create a context permissive for HTLV-1 antigen-specific cellular immune surveillance in selected patients with ATLL.

We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) Vβ clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, n = 38; Off-TKI, n = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling "≥7 years of TKI plus ≥1 year of DMR" and exhibiting CTL activation features-CD8 > CD4, memory > effector, and/or highly activated CTL clones on TCR Vβ repertoire-showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR Vβ clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds.

Background/Objectives: Follicular helper T-cell (TFH)-type lymphomas, including angioimmunoblastic T-cell lymphoma (AITL) and TFH lymphoma, not otherwise specified (TFH-NOS), are characterized by marked immune dysregulation in the tumor microenvironment. We investigated whether TFH-type lymphomas are enriched in immunosuppressive cells and explored immunologic changes associated with denileukin diftitox (DD) treatment. Methods: FOXP3-positive mononuclear cells were quantified by immunohistochemistry in lymph node specimens from 10 patients with TFH-type lymphoma and six with non-TFH-type T-cell lymphoma. Paired skin biopsy specimens obtained before and after DD treatment from two patients with AITL were evaluated for CD4, CD8, CD68, CD163, and FOXP3 expression. Longitudinal flow cytometric T-cell receptor Vβ repertoire analysis of CD8-positive T-cell subsets was performed in three patients with AITL treated with DD. Clinical responses were retrospectively assessed in seven patients with relapsed or refractory TFH-type lymphoma treated with DD. Results: TFH-type lymphomas showed significantly higher intra-tumoral FOXP3-positive cell densities than non-TFH-type lymphomas (p = 0.0024). In paired skin biopsies, DD treatment was associated with reductions in CD68- and CD163-positive macrophage-rich infiltrates and a suggested decrease in FOXP3-positive cells. Among seven patients treated with DD, the overall response rate was 86%, including one complete response and five partial responses. Responders showed selective Vβ over-representation patterns in effector and/or memory CD8-positive T-cell subsets, whereas such findings were not convincing in the non-responder. Conclusions: TFH-type lymphomas were associated with higher FOXP3-positive cell density than selected non-TFH-type comparators. DD treatment may be associated with changes in tissue immune infiltrates and peripheral CD8/TCR Vβ skewing in responding cases, although these findings remain exploratory and do not establish causality.

Objective Patients with acute myeloid leukemia (AML) transformed from myelodysplastic syndrome (MDS) have a poor prognosis, including those treated with azacitidine during the MDS phase; there is no standard for the care of these patients. Recently, azacitidine plus venetoclax (AZA/VEN) was reported to prolong the survival in treatment-naïve AML patients compared with AZA monotherapy. However, the results of AZA/VEN for AML transformed from MDS, particularly after AZA monotherapy, remain unclear. The present study therefore compared the clinical results of AZA/VEN treatment in these patients. Methods Data from MDS patients diagnosed at 10 institutions in Nagasaki Prefecture were collected. Thereafter, patients with transformed AML following AZA monotherapy during the MDS phase were selected, and their treatment response and survival were analyzed. Results The overall response (OR) rate, overall survival (OS), and event-free survival (EFS) were compared among patients treated with AZA/VEN (n=13), chemotherapy (intensive and low-intensity, n=35), AZA monotherapy (mAZA, n=15), and best supportive care (BSC, n=43) after AML transformation. The corresponding OR rates were 38.5%, 20.0%, and 6.7% for the AZA/VEN, chemotherapy, and mAZA groups, respectively (p=0.235). The respective median OS and EFS were 10.7 and 8.9 months for AZA/VEN, 3.2 and 2.0 months for chemotherapy, and 3.8 and 2.7 months for mAZA, and 1.7 months for BSC (OS only) (p=0.000023 for the OS and p=0.026 for the EFS), Conclusion Our findings suggest the superiority of AZA/VEN for AML patients with transformation from MDS following AZA monotherapy.

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post- transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.

Introduction: Prognosis of adult B-cell acute lymphoblastic leukemia (B-ALL) patients who relapsed after allogeneic stem cell transplant (SCT) was described to be extremely poor in the studies in the early 2010s. Although novel immunochemotherapeutic agents, inotuzumab ozogamicin (InO) and blinatumomab (Blina) improved treatment outcomes of relapse/refractory B-ALL patients, efficacy and safety of these agents in those with post-transplant relapse remain to befully elucidated. Methods: This retrospective study included 150 adult B-ALL patients (Philadelphia chromosome [Ph]-negative; n=95, Ph-positive; n=55), who underwent the first SCT between 2010 and 2020 in the 20 KSGCT institutions and experienced a hematological relapse. The median age at relapse after the first SCT was 43 years (18-71 years). Patients were divided into 2 groups depending on whether their relapse occurred before or after InO and Blina were approved in Japan in 2018, the pre-InO/Blina group (n=95) or the post-InO/Blina group (n=55). Efficacy and survival analyses were performed on the patients with Ph-negative B-ALL only, and safety analyses were performed on allpatients. Overall survival (OS) was defined as the interval from the date of relapse after the first SCT to the date of death. Fisher's exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazard model was used for multivariate analysis (MVA) for OS. Values of p<0.05 were considered to indicate statistical significance. Results: Of the 95 patients with Ph-negative B-ALL, 37 and 58 were in the post-InO/Blina group and the pre-InO/Blina group, respectively. Patient characteristics and transplant procedures were similar between the 2 groups, excluding larger proportions of patients treated with InO and/or Blina before the first SCT in the post-InO/Blina group in comparison with the pre-InO/Blina group (35% vs. 5%, respectively; p<0.01) and undergoing the first SCT in complete remission (CR) (84% vs. 57%, respectively; p=0.02). InO and Blina were used after relapse in the post-InO/Blina group in 17 (46%) and 20 (54%), respectively. The CR rate as the best response before a second SCT or the last observation and the OS rate in the post-InO/Blina group were significantly higher than the pre-InO/Blina group (CR: 77% vs. 36%, respectively; p<0.01, OS: 51% vs. 19% at 2 years after relapse, respectively; p<0.01). MVA for OS extracted relapse time as an independent risk factor (hazard ratio=0.51; p=0.02), besides disease status at the first SCT. Of the 34 patients in the post-InO/Blina group excluding 3 only with palliative care, chemotherapy, InO, and Blina were used as the first-line salvage therapy in 14, 13, and 7, respectively. There was a significant difference in the CR rates among the 3 groups (33% vs. 100% vs. 58%, respectively; p<0.01), but not in the OS (42% vs. 58% vs. 57% at 2 years after relapse, respectively; p=0.56). MVA for OS extracted PS at relapse as an independent risk factor, but neither InO nor Blina use as the first-line salvage therapy. Of the 150 patients in the entire cohort, 32 and 30 received InO and Blina after relapse, respectively, and 69 underwent a second SCT. Of the 32 patients treated with InO, no patient developed veno-occlusive disease (VOD) during InO treatments; however, 5 (29%) of the 17 who underwent a second SCT after InO did. Shorter duration (<2.5 months) between InO administration and a second SCT was associated with a higher risk of VOD (56% vs. 0%; p=0.03), but either age or numbers of alkylating agents included in conditioning regimens of a second SCT were not. Of the 30 patients treated with Blina, 16 (53%) and 2 (7%) developed cytokine release syndrome (CRS) of any grade and grade 3 to 4, respectively, and 4 (13%) and 1 (3%) developed immune effector cell-associated neurotoxicity syndrome of any grade and grade 3, respectively. CR at Blina initiation was associated with a lower risk of CRS (31% vs. 79%; p=0.01). Conclusions: The prognosis of adult Ph-negative B-ALL patients relapsed after the first SCT improved in the era of novel immunochemotherapeutic agents. Although safety profiles of InOand Blina treatments appeared acceptable, it is important to ensure an enough duration between InO administration and a second SCT to reduce VOD. Further investigations are warranted regarding the appropriate use of chemotherapy, InO, and Blina in these patients.

Adult T cell leukemia/lymphoma (ATLL) is a CD4-positive peripheral T cell lymphoma caused by human T cell lymphotropic virus type 1 (HTLV-1). Although ATLL is quite difficult to be cured, up-regulation of cellular immunity such as HTLV-1 Tax-specific cytotoxic T lymphocytes (CTLs) has been proved to be important to obtain long-term survival. At present, no efficacious method to activate ATLL-specific cellular immunity is available. This study aimed to investigate whether live attenuated varicella-zoster virus (VZV) vaccination to ATLL can activate HTLV-1 Tax-specific cellular immune response. A total of 3 indolent- and 3 aggressive-type ATLL patients were enrolled. All aggressive-type patients had the VZV vaccination after completing anti-ATLL treatment including mogamulizumab, which is a monoclonal antibody for C–C chemokine receptor 4 antigen, plus combination chemotherapy, whereas all indolent-type patients had the VZV vaccination without any antitumor treatment. Cellular immune responses including Tax-specific CTLs were analyzed at several time points of pre- and post-VZV vaccination. After the VZV vaccination, a moderate increase in 1 of 3 indolent-type patients and obvious increase in all 3 aggressive-type patients in Tax-specific CTLs percentage were observed. The increase in the cell-mediated immunity against VZV was observed in all indolent- and aggressive-type patients after VZV vaccination. To conclude, VZV vaccination to aggressive-type ATLL patients after mogamulizumab plus chemotherapy led to the up-regulation of HTLV-1 Tax-specific CTLs without any adverse event. Suppression of regulatory T lymphocytes by mogamulizumab may have contributed to increase tumor immunity in aggressive-type ATLL patients. Japan Registry of Clinical Trials number, jRCTs051180107.

Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12-14) and 9.4 months (range, 2.6-61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful follow-ups for non-IPCs in post-DLI patients.

AbstractPurposeAdult T‐cell leukemia/lymphoma (ATLL) is a relatively refractory peripheral T‐cell lymphoma caused by human T‐cell lymphotropic virus type 1 (HTLV‐1). The objective of this study was to investigate the characteristics of long‐term survivors with ATLL.MethodsWe conducted an observational study of 75 aggressive‐type ATLL patients. Flow cytometry was conducted to analyze HTLV‐1 Tax‐specific cytotoxic T‐lymphocytes (CTLs) and T‐cell receptor Vβ gene repertoire.ResultsWe first evaluated six long‐term survivors among 37 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy without mogamulizumab, a monoclonal antibody for C‐C chemokine receptor four antigen. Reversal of the CD4‐to‐CD8 ratio (CD4/CD8) in peripheral mononuclear cells was observed in all six patients. Three of these six patients showed reversed CD4/CD8 immediately after herpes virus infection. Four of these six patients who could be examined demonstrated long‐term maintenance of HTLV‐1 Tax‐specific CTLs. We subsequently identified four long‐term survivors among 38 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy plus mogamulizumab. All four patients showed reversed CD4/CD8, and three of the four patients contracted herpes virus infection during immunochemotherapy. Six of the total 10 patients were subjected to CTL analyses. Tax‐specific CTLs were observed, and the CTLs that were almost entirely composed of memory CTLs in all patients were recorded. HTLV‐1 provirus was also detected in all six patients.ConclusionsThese data suggest that Tax‐specific memory CTLs probably, together with anticancer agents, eradicate ATLL cells and exhibit long‐term preventive effects from relapse ATLL. Thus, the strong activation of cellular immunity, such as herpes virus infection, seems to be necessary to induce such a potent number of Tax‐specific CTLs.

This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted.

The hypomethylating agent azacitidine (AZA) significantly extends overall survival (OS) in patients with higher risk myelodysplastic syndromes (MDS), when compared with other conventional care regimens, including supportive care and low-dose and intensive chemotherapy. However, the effects of 5- and 7-day treatment schedules of AZA (AZA-5 and AZA-7, respectively) on the OS of MDS patients had not been compared prospectively. We started a phase 3 trial comparing the effects of AZA-7 and AZA-5 on MDS patients with refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T). However, this trial was prematurely terminated because of poor recruitment. Using all data, there was no significant difference in the OS of patients between AZA-7 (92 patients) and AZA-5 (95 patients), with the 2-year OS rates of AZA-7 and AZA-5 at 36.4% and 25.8%, respectively (P = 0.293). Adverse event profiles were similar between the two groups. Interestingly, data of the centrally diagnosed RAEB and RAEB-T cases showed that AZA-7 significantly prolonged the time to leukemia transformation compared with AZA-5 (P = 0.022), confirmed by multivariate analysis. Although this trial could not provide definite evidence, the results support the use of AZA-7 for RAEB and RAEB-T. (UMIN Clinical Trials Registry UMIN000009633).

Abstract Background: Although introduction of pediatric-type Berlin-Frankfurt-Munster (BFM) chemotherapy has markedly improved the prognosis of adolescent and young adult (AYA) patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-negative ALL), their higher toxicity has become an emerging issue with an increased post-remission mortality in AYA patients than pediatric patients. Allogeneic stem cell transplantation (allo-SCT) with myeloablative conditioning (MAC) regimens containing total body irradiation (TBI) is recognized as an important treatment option for patients with higher risk diseases. However, safety and efficacy of allo-SCT with TBI-MAC have not been fully investigated among AYA patients who received pediatric-type chemotherapy. Patients and methods: AYA was defined as 16 to 39 years old. Of the 143 AYA patients with Ph-negative ALL who underwent the first allo-SCT in the first remission between 2007 and 2016 at the 20 institutions, 106 patients who were treated with one BFM chemotherapy regimen before transplant and were conditioned with MAC regimens containing more than or equal to 8 Gy of TBI dose. The reasons for the transplant were surveyed with a multi-answer questionnaire. Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Fisher's exact test was used to compare binary variables. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were evaluated with Gray's test, considering relapse and NRM as a competing risk, respectively. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Factors associated with at least borderline significance (p < 0.20) in univariate analyses were subjected to multivariate analysis. The Fine-Gray and Cox proportional hazard model were used for multivariate analysis of risk factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance. Results: Of the 106 patients included in this study, 61 were male, and 45 were female. The median age at transplant was 29 years (range, 16-39 years). Donor types were related, unrelated, and cord blood in 47 (44%), 47 (44%), and 12 (12%) patients, respectively. The difficulty of continuing chemotherapy due to side effects as the reason for transplant was included in 13 patients (12%). As chemotherapy before transplant, pediatric-type and adult-type regimens were used in 56 (53%) and 50 patients (47%), respectively. There was no significant difference in baseline characteristics and transplant procedures between the pediatric-type group and the adult-type group, except for proportion of patients over 30 years (14% vs. 64%, respectively; p < 0.01), those with more than or equal to 2 of hematopoietic cell transplant comorbidity index (13% vs. 36%, respectively; p < 0.01), and transplant between 2007 and 2011 (36% vs. 64%, respectively; p < 0.01). The CI of NRM, the OS rates, and the CI of relapse were not significantly different between two groups (NRM: 4% vs. 12% at three years after transplant, respectively; p = 0.26), (OS: 86% vs. 70%, respectively; p = 0.14), and (relapse: 16% vs. 24%, respectively; p = 0.32), respectively. Multivariate analysis for NRM revealed that more than or equal to 1 of performance status at transplant (hazard ratio [HR] = 4.8; p < 0.01) and transplant due to side effects of chemotherapy (HR = 3.5; p = 0.04) were identified as independent risk factors, but not pediatric-type chemotherapy (HR = 0.48; p = 0.23). The proportions of transplant due to side effects of chemotherapy were similar between two groups (13% vs. 12%, respectively; p = 1). No independent prognostic factor for OS was found, while transplant between 2007 and 2011 (HR = 2.5; p = 0.04) was extracted as an independent risk factor of relapse. Regarding transplant complications, significant differences were not shown in CI of grade II to IV acute graft-versus-host disease (GVHD), chronic GVHD, bacteremia, cytomegalovirus reactivation, hemorrhagic cystitis, and avascular necrosis between two groups. No characteristic cause of NRM was found in the pediatric-type group. Conclusion: These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric-type chemotherapy. Disclosures Kimura: MSD: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Kyowa Kirin: Honoraria; Chugai Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical: Honoraria; Eisai: Honoraria; Nippon Kayaku: Honoraria; Takeda Pharmaceutical: Honoraria; SymBio Pharmaceutical: Honoraria. Usuki: MSD: Speakers Bureau; Alexion: Speakers Bureau; Pfizer: Research Funding; Kyowa Kirin: Research Funding, Speakers Bureau; Eisai: Speakers Bureau; Nippon shinyaku: Research Funding, Speakers Bureau; Astellas-Amgen-Biopharma: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Takeda: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding; Ono: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Daiichi Sankyo: Research Funding, Speakers Bureau; Symbio: Research Funding, Speakers Bureau; Gilead: Research Funding; Abbvie: Research Funding; Astellas: Research Funding, Speakers Bureau; Mundipharma: Research Funding; Yakult: Speakers Bureau; PharmaEssentia: Speakers Bureau. Sakaida: Bristol Myers Squibb: Research Funding; Chugai: Research Funding; Ono: Research Funding; Kyowa Kirin: Research Funding. Fujisawa: Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding. Handa: Abbvie: Honoraria; MSD: Research Funding; Shionogi: Research Funding; Sanofi: Honoraria, Research Funding; Ono: Honoraria; BMS: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Research Funding; Celgene: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; Takeda: Honoraria, Research Funding. Hatta: Bristol-Myers Squibb: Honoraria; Novartis KK: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical.: Honoraria. Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding; Sanofi: Research Funding; MSD: Honoraria.

We present the case of a patient with multiple tyrosine kinase inhibitor (TKI)-refractory chronic phase chronic myeloid leukemia (CP-CML) with a T315I mutation of abl1. Dasatinib, a second-generation TKI, was administered as the initial treatment but achieved neither a cytogenetic nor molecular response. A mutational analysis of abl1 revealed that the patient had a T315I mutation. The patient was then administered ponatinib, a third-generation TKI, which is thought to be effective against T315I; however, the complete blood counts became within normal limits, and neither a cytogenetic nor molecular response was achieved. However, the patient has maintained a healthy chronic phase (with no blast crises) for more than 5½ years since the diagnosis of CP-CML. T-cell receptor (TCR) repertoire analyses using peripheral blood revealed a remarkable clonal expansion of effector cytotoxic T lymphocytes (CTLs) that contained TCR V beta 13.6. We observed the clonal expansion of naïve CTLs with TCR V beta 13.6; however, no clonality was observed in the memory CTLs. The naïve and effector CTLs persisted at very high percentages since the seventh month after starting dasatinib. The CTLs could not have led to the molecular response; therefore, there might be plenty of CML stem cells remaining in the bone marrow. Therefore, although the CTLs might have prevented the disease from developing blast crises over more than 5 years, the CTLs might not have been able to become memory CTLs.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is a serious complication that negatively affects the prognosis and quality of life of patients who receive allogeneic hematopoietic stem cell transplantation (alloHSCT). Antithymocyte globulin (ATG) is one of the second-line treatments for SR-aGVHD. We retrospectively evaluated Karnofsky Performance Status (KPS) recovery and clinical response in 11 patients who received the response-guided low-dose ATG treatment for SR-aGVHD after allo-HSCT using alternative donors. The median dose of ATG per cycle was 1.0 mg/kg (range, 1.0-1.25 mg/kg) and the median number of cycles of ATG was 2 (range, 1-4). The overall response rate was 63.6%, and the estimated overall survival rate at 1 year was 63.6%. Two out of seven patients who survived 1 year after the response-guided ATG treatment had KPS of 80 or higher. The remaining 5 patients had KPS of lower than 80 due to moderate chronic GVHD (cGVHD) and/or >= grade 3 infectious complications. Based on the poor prognosis of patients with SR-aGVHD, the response-guided ATG treatment represents one therapeutic option. The present results also suggest that chronic GVHD and infectious complications after the response-guided ATG treatment were associated with decreased KPS recovery and impaired social function.

Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.04.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

Introduction: Tucidinostat (HBI-8000) is a class I selective oral histone deacetylase inhibitor with immunomodulatory effects including enhanced cell-mediated toxicity, with activation of enhanced tumor-specific cytotoxic T-lymphocytes and suppression of regulatory T-lymphocytes. In the phase 1 study in Japanese patients with relapsed or refractory (R/R) non-Hodgkin lymphoma including those with adult T-cell leukemia-lymphoma (ATL), tucidinostat showed tolerability and manageable safety profile as well as efficacy signals especially in patients with ATL. This phase 2 study further evaluated the efficacy and safety of tucidinostat in patients with R/R aggressive ATL. Method: Key inclusion criteria included; histopathological or cytological diagnosis of ATL of acute, lymphoma or unfavorable chronic types; relapsed or refractory disease after receiving prior systemic therapy including mogamulizumab or ≥1 prior systemic therapy with cytotoxic chemotherapy in case of intolerance/contraindication for mogamulizumab. Patients were to receive tucidinostat 40 mg twice a week with a 28-day cycle. Tucidinostat was continued until disease progression or the development of unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) and safety. (NCT02955589) Results: A total of 23 patients were treated with tucidinostat and were included in both efficacy and safety analysis sets. The median age was 72 years (range: 60-89), and 35% (8/23) were female. The median number of prior chemotherapies was 2. All patients had prior mogamulizumab treatment. As for ATL subtype, acute, lymphoma and unfavorable chronic types constitute 57% (13/23), 35% (8/23), and 9% (2/23), respectively. The median time from last treatment to the initiation of the study drug was 89 days (range: 30-496). Out of 23 patients, 7 showed objective responses including 1 complete response, and ORR was 30% [95% CI: 13, 53]. ORR by ATL subtypes were 46% (6/13) in acute type, 13% (1/8) in lymphoma type, and 0% (0/2) in unfavorable chronic type. Median PFS and median DOR were 1.7 months and 6.5 months, respectively. All 23 patients experienced adverse events (AEs). Overall, 78% (18/23) of patients had AEs of Grade ≥3 severity. Most of AEs were hematologic including thrombocytopenia and neutropenia, followed by non-hematological AEs including decreased appetite and malaise. Conclusions: The results of the present study are demonstrating efficacy in patients with R/R aggresive ATL with prior treatment history of mogamulizumab. Toxicities were mainly hematologic, which were manageable with supportive care and dose modifications. This phase 2b study demonstrated that tucidinostat had clinically meaningful efficacy and an acceptable safety profile in R/R aggressive ATL. The research was funded by: HUYA Bioscience International Keywords: Aggressive T-cell non-Hodgkin lymphoma, Therapeutics and Clinical Trials in Lymphoma - Other Conflicts of interests pertinent to the abstract K. Izutsu Research funding: HUYA Bioscience International A. Utsunomiya Consultant or advisory role: HUYA Bioscience International, JIMRO Honoraria: Novartis Pharma, Kyowa Kirin, Daiichi Sankyo, Bristol-Myers Squibb, Celgene, Pfizer, Minophagen Pharmaceutical, Janssen Pharmaceutical, Chugai Pharmaceutical S. Yoshida Research funding: Kyowa Kirin Y. Imaizumi Honoraria: Celgene, Kyowa Kirin, Eisai , Bristol-Myers Squibb, Sumitomo Dainippon Pharma, SymBio Pharmaceuticals K. Kato Consultant or advisory role: AbbVie, AstraZeneca, Celgene, Chugai Pharmaceutical, Eisai, Janssen Pharmaceutical, Novartis Pharma, Daiichi Sankyo, Ono Pharmaceutical Honoraria: Takeda Pharmaceutical, MSD, Kyowa Kirin, Janssen Pharmaceutical, Celgene, Ono Pharmaceutical, Mundipharma, Sumitomo Dainippon Pharma, Bristol-Myers Squibb Research funding: Chugai Pharmaceutical, Takeda Pharmaceutical, Kyowa Kirin, AbbVie, Eisai, Janssen Pharmaceutical, Celgene, Ono Pharmaceutical, Novartis Pharma, Daiichi Sankyo S. Kusumoto Honoraria: Chugai Pharmaceutical H. Shibayama Consultant or advisory role: Chugai Pharmaceutical, Ono Pharmaceutical, AbbVie, AstraZeneca Honoraria: Takeda, Novartis, Celgene, Janssen, Chugai, Kyowa Kirin, Ono, Eisai, Nippon Shinyaku, Otsuka, Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Sanofi, Fujimoto Research funding: Janssen, Novartis, Chugai, Ono, Eisai, HUYA Bioscience International, AbbVie, AstraZeneca, Sanofi, Astellas, Teijin, Shionogi, Taiho, Celgene, Takeda, MSD, Sumitomo Dainippon Pharma, Nippon Shinyaku, Daiichi Sankyo K. Shimoda Consultant or advisory role: Novartis Pharma, Takeda Pharmaceutical, Bristol-Myers Squibb, Celgene Research funding: Perseus Proteomics, Pharma Essentia Japan, AbbVie, Astellas Pharma, MSD, Chugai Pharmaceutical, Kyowa Kirin, Pfizer, Novartis Pharma, Otsuka Pharmaceutical, Asahi Kasei Medical Y. Takamatsu Research funding: Takeda Pharmaceutical, Ono Pharmaceutical, Chugai Pharmaceutical, Kyowa Kirin, Taiho Pharmaceutical K. Tsukasaki Consultant or advisory role: Daiichi Sankyo, Ono Pharmaceutical, HUYA Bioscience International, Yakult Pharmaceutical Industry Honoraria: Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai, Kyowa Kirin, Mundipharma, Takeda Pharmaceutical Research funding: Daiichi Sankyo, HUYA Bioscience International, Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai S. Makita Honoraria: Celgene/BMS, Daiichi Sankyo, Eisai, Novartis Pharma, Takeda Pharmaceutical K. Yonekura Honoraria: AbbVie, Celgene, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen Pharmaceuticals, Kaken Pharmaceutical, Kyowa Kirin, Maruho, Minophagen Pharmaceutical, Novartis Pharma, Sanofi, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Japan M. Gillings Employment or leadership position: HUYA Bioscience International Stock ownership: HUYA Bioscience International H. Onogi Employment or leadership position: HUYA Bioscience International K. Tobinai Consultant or advisory role: Celgene, Zenyaku Kogyo, HUYA Bioscience International, Daiichi Sankyo, Takeda Pharmaceutical, Mundipharma, Ono Pharmaceutical Honoraria: Zenyaku Kogyo, Eisai, Takeda Pharmaceutical, Mundipharma, HUYA Bioscience International, Kyowa Kirin, Celgene, Chugai Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical Industry, Daiichi Sankyo, Solasia Pharma

The efficacy of azacitidine (AZA) on survival of lower risk (LR) - myelodysplastic syndromes (MDS) is controversial. To address this issue, we retrospectively evaluated the long-term survival benefit of AZA for patients with LR-MDS defined by International Prognostic Scoring System (IPSS). Using data from 489 patients with LR-MDS in Nagasaki, hematologic responses according to International Working Group 2006 and overall survival (OS) were compared among patients that received best supportive care (BSC), immunosuppressive therapy (IST), erythropoiesis-stimulating agents (ESA), and AZA. Patients treated with AZA showed complete remission (CR) rate at 11.3%, marrow CR at 1.9%, and any hematologic improvement at 34.0%, with transfusion independence (TI) of red blood cells in 27.3% of patients. and platelet in 20% of patients, respectively. Median OS for patients received IST, ESA, BSC, and AZA (not reached, 91 months, 58 months, and 29 months, respectively) differed significantly (P < .001). Infection-related severe adverse events were observed in more than 20% of patients treated with AZA. Multivariate analysis showed age, sex, IPSS score at diagnosis, and transfusion dependence were significant for OS, but AZA treatment was not, which maintained even response to AZA, and IPSS risk status at AZA administration was added as factors. We could not find significant survival benefit of AZA treatment for LR-MDS patients.