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B Introduction: b We conducted a multinational, multicenter retrospective registry study to better define the treatment patterns and survival outcomes of newly diagnosed patients with mantle cell lymphoma (MCL) in the Asia-Pacific region. Higher proportion of elderly patients received R-CHOP or R-CHOP-like regimens, while cytarabine-containing regimens were more frequently administered in young patients (Figure 1B). The most frequently administered 1st line regimen was R-CHOP or R-CHOP-like regimens ( I n i = 146), followed by cytarabine-containing regimens ( I n i = 78) including R-Hyper-CVAD ( I n i = 56), and bendamustine-rituximab ( I n i = 22) (Figure 1A). [Extracted from the article]

Compared with 180 matched patients who received non-pola-based therapy, there was a significantly higher ORR in Pola-based salvage treatments (62.8% vs. 33.3%, hazard ratio [HR] 3.52, 95% confidence interval [CI] 1.39-8.95, I p i < 0.01). Treatments of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) represent an unmet clinical need. Thirty-five patients who received Pola-based treatment (Pola-BR 54.3% and Pola-R 45.7%) were included. [Extracted from the article]

EXCELLENT OUTCOMES OF SUBCUTANEOUS PANNICULITIS-LIKE T-CELL LYMPHOMA TREATED WITH CYCLOSPORIN-BASED REGIMEN, A MULTICENTER RETROSPECTIVE STUDY IN THAILAND The patient demographic data, treatment regimens which divided into conventional chemotherapy or immunosuppressive agents, and treatment outcomes were retrieved from the Thai lymphoma registry database. B Background: b Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma, characterized by primary cutaneous tissue involvement mimicking inflammatory panniculitis. [Extracted from the article]

Abstract Background Hematopoieticic stem cell transplantation is the only therapeutic option that can cure thalassemia disease. Reduced intensity hematopoietic stem cell transplantation (RI-HSCT) has demonstrated a high cure rate with minimal complications compared to other options. Because RI-HSCT is very costly, economic justification for its value is needed. This study aimed to estimate the cost-utility of RI-HSCT compared with blood transfusions combined with iron chelating therapy (BT-ICT) for adolescent and young adult with severe thalassemia in Thailand. Methods A Markov model was used to estimate the relevant costs and health outcomes over the patients’ lifetimes using a societal perspective. All future costs and outcomes were discounted at a rate of 3% per annum. The efficacy of RI-HSCT was based a clinical trial including a total of 18 thalassemia patients. Utility values were derived directly from all patients using EQ-5D and SF-6D. Primary outcomes of interest were lifetime costs, quality adjusted life-years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) in US ($) per QALY gained. One-way and probabilistic sensitivity analyses (PSA) were conducted to investigate the effect of parameter uncertainty. Results In base case analysis, the RI-HSCT group had a better clinical outcomes and higher lifetime costs. The incremental cost per QALY gained was US $ 3,236 per QALY. The acceptability curve showed that the probability of RI-HSCT being cost-effective was 71% at the willingness to pay of 1 time of Thai Gross domestic product per capita (GDP per capita), approximately US $ 4,210 per QALY gained. The most sensitive parameter was utility of severe thalassemia patients without cardiac complication patients. Conclusion At a societal willingness to pay of 1 GDP per capita, RI-HSCT was a cost-effective treatment for adolescent and young adult with severe thalassemia in Thailand compared to BT-ICT.

Introduction: Peripheral blood stem cells (PBSCs) are the most common source of stem cell transplantation, which depends on an adequate number of CD34+ cells. Although pre-apheresis CD34+ cell count is a standard guide for the collection, it is not always available. This study aimed to evaluate complete blood count parameters for predicting successful one-day autologous PBSC collection., Methods: Data from the patients who underwent autologous PBSC collection at a tertiary care hospital were retrospectively reviewed., Results: There were 123 patients (185 leukapheresis procedures). Successful PBSC collection (CD34+ cells ≥4.0 × 10 6 cells/kg) was obtained in 85 patients (69.1%), of which 55 (44.7%) were successfully obtained on the first day. The median CD34+ collection efficiency was 44.1%. The mean platelet loss during apheresis was 39.9%. The adverse event rate was 18.9%. Patients in whom PBSCs were collected within one day were less likely to experience adverse effects related to leukapheresis. Pre-apheresis CD34+ cells ≥10 cells/μLand combined white blood cell (WBC) counts ≥5 × 10 9 /L and/or monocyte ≥10% were independently associated with the successful one-day PBSC collection (adjusted odds ratio 24.06, 95% confidence interval [CI] 5.30-109.10, p < 0.001; and 6.94, 95% CI 1.35-35.79, p = 0.021, respectively). Only pre-apheresis CD34+ cells had a strong correlation with the total stem cell yield., Conclusions: To reduce the complication of leukapheresis, the combined pre-apheresis WBC ≥5 × 10 9 /L and/or monocyte ≥10% is a practical parameter to initiate a successfully one-day PBSC collection with or without pre-apheresis CD34+ cell results., (© 2024 John Wiley & Sons Ltd.)

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement., Competing Interests: Declarations. Ethics approval: The study has been approved by The Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, which the following study in compliance with the International guidelines for human research protection as Declaration of Helsinki, The Belmont Report, CIOMS Guideline and International Conference on Harmonization in Good Clinical Practice (ICH-GCP).(Certificate of Full Board Approval (COA No. 0510/2023)) Informed consent was obtained from all patients for being included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.1% increase in allogeneic transplants and a 3.1% increase in autologous transplants, an overall increase of 4.4% compared to the numbers in 2019. With respect to the donor source, haploidentical transplants increased significantly by 18.6%, related transplants by 8.8%, and cord blood transplants (CBT) by 9.2%. However, the number of unrelated transplants, excluding CBT, decreased for the first time by 8.2%. As a result, COVID-19 facilitated the growth of haploidentical transplants due to cross-border restrictions. Regarding the changes in the total number of transplants by country/region in 2020, it increased by 2,048 transplants in China, followed by Japan (210 transplants) and Korea (230 transplants); however, 14 of the 22 countries and regions decreased their number of transplants in 2020 compared to the previous year. There was no correlation between the increase or decrease in the number of transplants in 2020 and the Gross National Income (GNI) per capita of each country/region in 2020, as well as Domestic General Government Health Expenditure as a percentage of General Government Expenditure (GGHE-D/GGE). In 2021, the total number of transplants in this region was 34,754. With the exception of a few countries/regions that decreased the number of transplants in 2020, most countries/regions have started to see a recovery in 2021. The COVID-19 pandemic significantly affected the supply chain and logistics involved in HCT rather than its numbers; however, we have found ways to overcome logistical challenges to carry out transplant medicine without delay, even under these circumstances., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website. MI, AS, AAH, NK, MB, and SO are editors of Blood Cell Therapy. They were not involved in the editorial evaluation and the decision to accept this article for publication., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

Aims: Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs., Methods: MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes., Results: Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCA A1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes., Conclusions: Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dengue virus infection is an intriguing illness. It is traditionally thought of as a self-limited and nonpersistent disease., Objectives: We report a case with persistent dengue virus genome detectable in hematopoietic cells of a person with remote infection., Methods: A patient with multiple myeloma in remission was prepared for peripheral blood stem cell (PBSC) transplantation. Plasma and G-CSF-stimulated, mobilized PBSCs were collected. Dengue-specific reverse transcription polymerase chain reaction (RT-PCR) was performed in both pre- and post-stimulated blood specimens. Anti-dengue antibodies by ELISA and by neutralization assay were measured before and after the stem cell mobilization., Results: The viral genome was detected only in the PBSC of the post-G-CSF-stimulated specimens. Anti-dengue antibodies were negative and positive, by ELISA and neutralization assays, respectively, both before and after stem cell mobilization., Conclusion: Our findings reveal a persistent infection. Whether and how this strain may interact with subsequent serotype(s) remains to be elucidated., (© 2023 Soraya Thaivanich et al., published by Sciendo.)

Several prognostic models have been introduced to predict outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Endothelial activation and stress index (EASIX) is a surrogate of endothelial dysfunction which has been shown to predict outcomes of patients with various hematologic malignancies. However, the prognostic implication of EASIX for DLBCL is limited and warrants exploration. We conducted a retrospective study enrolling adult DLBCL patients including a discovery cohort from the single-centered university hospital database and a validation cohort from the independent nationwide multi-center registry. EASIX scores were calculated using creatinine, lactate dehydrogenase, and platelet levels. The receiver operating characteristic curve analysis was used to determine optimal cutoff. Statistical analysis explored the impact of EASIX on survival outcomes. A total of 323 patients were included in the discovery cohort. The optimal EASIX cutoff was 1.07 stratifying patients into low (53.9%) and high EASIX (46.1%) groups. Patients with high EASIX had worse 2-year progression-free survival (PFS) (53.4% vs. 81.5%, p<0.001) and overall survival (OS) (64.4% vs. 88.7%, p<0.001) than patients with low EASIX. Multivariate analysis revealed that older age, bulky disease, impaired performance status, and high EASIX were associated with an unfavorable OS. In the validation cohort of 499 patients, the optimal EASIX cutoff was 1.04. Similar to the discovery cohort, high EASIX score was associated with high-risk diseases, worse PFS, and inferior OS. In conclusion, EASIX score was significantly associated with survival outcomes and may be used as a simple prognostic tool to better risk-classify DLBCL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The number of hematopoietic stem cell transplantations (HCTs) is increasing annually worldwide, and the Asia-Pacific (AP) region is no exception. We report on the absolute number of HCTs in 2018 and 2019 and the trends in graft selection and disease indication in the past few decades. In 2018, 24,292 HCTs were performed in the AP region, of which 8,754 (36.0%) were autologous and 15,538 (64.0%) were allogeneic. Among the allogeneic HCTs, 10,552 (67.9%) of the recipients were related to their donors, whereas 4,986 (32.1%) were unrelated. In 2019, 27,583 HCTs were reported, of which 17,613 (63.9%) were allogeneic and 9,970 (36.1%) were autologous. Although, in 2010, there was a nearly equal number of related and unrelated HCTs, the difference has shown an annual increase, with more than double (2.05) the number of related than unrelated HCTs in 2019. Recent trends in the AP region show that peripheral blood has overwhelmingly surpassed the bone marrow as a graft source for both related and unrelated HCTs, with the haploidentical donor type being preferred; however, their trends in each country/region were quite different among countries/regions. In 2019, the main conditions requiring HCT were acute myelogenous leukemia (n=6,629 [24.0%]), plasma cell disorders (PCD) (n=4,935 [17.9%]), malignant lymphoma (ML) (n=4,106 [14.9%]), acute lymphoblastic leukemia (AML) (n=3,777 [13.7%]), myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm (n=1,913 [6.9%]), severe aplastic anemia (n=1,671 [6.1%]), and hemoglobinopathy (n=910 [3.3%]). PCD and ML were the main indications for autologous HCT, and the number of PCD cases has grown more prominent than the corresponding of ML. The increased number of allogeneic transplants for hemoglobinopathy remains prominent, as well as that of AML and acute lymphocytic leukemia for the past 5 years. There was a significant regional variation in the number of facilities performing HCTs, ranging from one in Mongolia and Nepal to 313 in Japan, and differing regional densities varying from 0.1 in Indonesia and Pakistan to 24.7 in Japan. The total transplant density per 10 million population in each country/region also differed (0.2 in Indonesia and 627 in New Zealand). This annual Activity Survey aims to help all participating countries/regions understand the changes in HCT, serve as an asset in promoting HCT activities in the AP region, and be used as a reference for comparison with other registries from Europe and the United States., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website. MI, AS, MB, AAH, and SO are editors of Blood Cell Therapy. They were not involved in the editorial evaluation and the decision to accept this article for publication., (Copyright Ⓒ2023 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.

Background: The survival rate of adult patients with Hodgkin lymphoma (HL) depends on the responses to standard chemotherapy, radiotherapy, or combined therapy. Resource-limited countries face numerous obstacles in supporting patients with HL who undergo chemotherapy, especially in advanced stages., Aim: To analyze the survival outcomes of adult patients with HL after combined-modality treatment (CMT) with involved-field or non-involved-field radiotherapy., Methods and Results: We retrospectively reviewed the medical records of 90 adult patients with HL who received CMT at Rajavithi Hospital, Bangkok between 2007 and 2021. Patients with stage I-IV disease received different therapies depending on their risk group. The risk groups were evaluated according to initial response, bulky disease, and B symptoms. Patients (n = 90) who underwent CMT were followed up for 34.7 months (range, 1-141 months). The median follow-up periods of early and advanced-stage patients were 53.1 months and 23.5 months, respectively. The estimated 5-year overall survival (OS) and progression-free survival (PFS) rates of patients with advanced-stage diseases were 85% and 62%, respectively. There was a difference in the 3-year overall survival among advance-stage patients who underwent ABVD (94%) compared to those administered BEACOPPesc (50%), and the 3-year PFS (84%) among patients who underwent ABVD was higher than that among those administered BEACOPPesc (66%). Radiotherapy increased toxicity but did not improve the survival rate., Conclusion: Chemotherapy administered to patients with advanced-stage adult HL was more effective than BEACOPPesc when ABVD was administered. Our findings are relevant for hospitals with limited resources., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population., Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients., Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%., Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT., Competing Interests: Conflicts of interest All authors report no conflict of interest., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is a challenging condition to treat, and there is an unmet clinical need for effective therapies. Recently, polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADC), combined with bendamustine-rituximab (BR), has been approved for R/R DLBCL patients. However, real-world data on Pola-based regimens in R/R DLBCL patients, especially in Thailand, are limited. This study aimed to evaluate the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. Thirty-five patients who received Pola-based treatment were included in the study, and their data were compared to 180 matched patients who received non-Pola-based therapy. The overall response rate (ORR) in the Pola group was 62.8%, with complete remission and partial remission rates of 17.1% and 45.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 10.6 months and 12.8 months, respectively. The study found a significantly higher ORR in Pola-based salvage treatments compared to non-Pola-based therapy (62.8% vs. 33.3%). The survival outcomes were also significantly superior in the Pola group, with longer median PFS and OS than the control group. Grades 3-4 adverse events (AEs) were mainly hematological, and they were tolerable. In conclusion, this study provides real-world evidence of the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. The results of this study are promising and suggest that Pola-based salvage treatment could be a viable option for R/R DLBCL patients who have limited treatment options., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A tool for estimating risk of febrile neutropenia (FN) after chemotherapy, namely the FEbrile Neutropenia after ChEmotherapy (FENCE) score, has been developed but has not been widely validated. This study aimed to validate the FENCE score as a tool for predicting granulocyte colony-stimulating factor (G-CSF) breakthrough FN among patients with lymphoma who underwent chemotherapy., Methods: This was a prospective observational study of treatment-naive adult patients with lymphoma who underwent their first cycle of chemotherapy between 2020 and 2021. The patients were followed up until the next cycle of chemotherapy to identify any infection events., Results: Among the 135 patients with lymphoma, 62 (50%) were men. In a comparison of the value of each FENCE parameter for predicting G-CSF breakthrough infection, the parameter of advanced-stage disease showed high sensitivity of 92.8%, and receipt of platinum chemotherapy showed high specificity of 95.33%. With a FENCE score of 12 as a cutoff for low risk, analysis across all patients with lymphoma resulted in a high AUROCC of 0.63 (95% CI = 0.5-0.74%; p = 0.059), and analysis across only patients with diffuse large B-cell lymphoma (DLBCL) resulted in an AUROCC of 0.65 (95% CI = 0.51-0.79%; p = 0.046). With a cutoff point of 12, FENCE score can predict breakthrough infection events at 30.0% (95% CI = 17.8-47.4%)., Conclusion: This study divided patients with lymphoma into risk groups according to FENCE score, showing that this instrument has discriminatory ability in predicting FN events, these being more likely to occur in patients in the intermediate- and high-risk groups. Multicenter studies are needed to validate this clinical risk score., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thungthong, Chamnanchanunt, Suwanban, Nakhahes, Iam-arunthai, Akrawikrai, Bunworasate and Rojnuckarin.)

Background: Cytokine-induced killer (CIK) cells are a heterogeneous group of immune cells that exert potent MHC-unrestricted cytotoxicity toward various cancer cells in both solid and hematological malignancies., Objective: The purposes of this study were to compare the expansion and characteristics of cytokine-induced killer cells between a standard culture method and a gas-permeable culture method and to develop a clinical-scale expansion protocol for cytokine-induced killer cells using a gas-permeable culture method., Methods: We compared the absolute cell number, fold change, cell subsets, activation markers, cytokine concentrations, and cytotoxicity toward myeloid leukemia cell lines between cytokine-induced killer cells expanded using two different culture methods. Then, we determined the ability to achieve clinical-scale expansion of cytokine-induced killer cells using the gas-permeable culture method., Results: Cytokine-induced killer cells in the gas-permeable culture method group exhibited significantly better expansion but maintained similar cell subsets, activation markers, and cytotoxicity to those in the standard culture method group. In addition, we successfully manufactured cytokine-induced killer cells for clinical use using the gas-permeable culture method. We also showed the clinical efficacy of allogeneic cytokine-induced killer cells produced by the gas-permeable culture method in a patient with acute myeloid leukemia that relapsed after allogeneic hematopoietic stem cell transplantation. This patient maintained ongoing disease remission for 2 years with minimal side effects after cytokine-induced killer cell infusion., Conclusions: We successfully developed a simple and effective protocol for the ex vivo expansion of cytokine-induced killer cells using the gas-permeable culture method for clinical application.

Introduction: Myelodysplastic syndromes (MDS) predominantly present with varying degrees of cytopenia, while myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) exhibit proliferative features. Genetic defects underlying different complete blood count (CBC) alterations remain to be defined., Objective: We aimed to evaluate mutations and impacts on abnormal blood counts in MDS and MDS/MPN., Method: MDS and MDS/MPN patients were recruited and sequenced by targeted next-generation sequencing. Clinical parameters, especially CBC, were evaluated for the association with genetic abnormalities and clinical outcomes., Results: A total of 168 patients with myeloid neoplasms were recruited (92 cases of low-risk MDS, 57 cases of high-risk MDS and 19 cases of MDS/MPN). Compared to low-risk MDS and MDS/MPN, patients with high-risk MDS were presented with more severe neutropenia with 17.5% showing absolute neutrophil counts (ANC) lower than 0.5 × 10 9 /L. Patients with MDS/MPN more commonly harboured mutations and had a higher number of mutations per case than low-risk MDS (94.7% vs. 56.5%; p  < 0.001 and 3 vs. 1; p  < 0.001, respectively). Patients with SF3B1 mutations showed lower haemoglobin levels than wild-type (7.9 vs. 8.4 g/dL, p  = 0.02), but were associated with normal platelet counts (286 vs. 93 × 10 9 /L; p  < 0.001). Patients with U2AF1 mutations were associated with more severe leukopenia than wild-type (3 vs. 4.18 × 10 9 /L; p  = 0.02). KRAS mutations were associated with monocytosis ( p  < 0.001). Multivariate analysis revealed high-risk MDS, MDS/MPN, severe neutropenia (ANC < 0.5 × 10 9 /L), and mutations in ASXL1 and SETBP1 were associated with inferior survival outcomes., Conclusion: Certain mutations were related to more severe anaemia, lower white blood cell count or monocytosis in Asian MDS and MDS/MPN patients.

Background: Unexplained cytopenia (UC) and low-risk myelodysplastic syndrome (MDS) are distinguished mainly by morphologic dysplasia, which sometimes shows inter-observer discrepancy. We hypothesized that gene mutations are strong prognostic factors for these low-risk patients., Materials and Methods: We enrolled patients from 4 medical centers with unexplained cytopenia of at least 1 lineage. Diagnosis of low-risk MDS was made according to WHO 2016 classification and a revised international prognostic scoring system (R-IPSS) score of ≤ 3.5. DNA was extracted from bone marrow or blood and sequenced by targeted next generation sequencing (NGS)., Results: One hundred twenty-one patients were recruited: 25% with UC and 75% with low-risk MDS. Complete blood counts were similar, but low-risk MDS patients carried higher numbers of mutations (1 vs. 0; P = .04) than UC patients. Overall, the most frequent mutated genes were TET2 (14.6%), SF3B1 (12.2%), and ASXL1 (9.7%). Survival rates of low-risk MDS patients versus UC patients were not significantly different. UC patients and low-risk MDS patients without genetic abnormalities showed superior 5-year progression free survival compared to MDS patients with mutations (100% vs. 76.0%; P = .005). Overall, ASXL1 mutations were associated with decreased 4-year overall survival compared to wild-type (59% vs. 31%; P = .01). In a multivariate analysis, ASXL1 and DNMT3A mutations in low-risk MDS patients were associated with a higher risk of disease progression with hazard ratios of 7.88 (95% CI 1.76-35.32, P = .01) and 7.45 (95% CI 1.61-34.46, P = .01), respectively., Conclusion: Mutation detection is important for proper risk stratification of patients presenting with idiopathic cytopenia., (Copyright © 2021. Published by Elsevier Inc.)

Competing Interests: All authors report no conflict of interest.

Programmed cell death (PD)/PD-ligands (PD-Ls) pathway plays an important role in the regulation of physiologic immune response. Several cancers, including lymphoma exhibit abnormal PD-1/PD-Ls expression, which may contribute to treatment failure, progression, and inferior outcomes. PD-1/PD-Ls expression has predominantly been described in B-cell lymphoma; such data in peripheral T-cell lymphoma (PTCL) is limited. We described PD-1/PD-Ls expression patterns and associations with clinical characteristics and outcomes, in patients with systemic PTCLs. Correlation between PD-1/PD-Ls expression and outcomes was analyzed in patients who received lymphoma-specific therapy. PD-1/PD-Ls expression was observed across all common PTCL histologies at different proportions (PD-1 0%-76.9%, PD-L1 38.5%-62.5%, and PD-L2 62.5%-100%) with PD-1 being highly expressed in angioimmunoblastic T-cell lymphoma. Baseline characteristics were comparable between PD-1/PD-Ls expression status. Of 47 patients who received lymphoma-specific therapy, outcomes were similar across all PD-L1/PD-L2 subgroups. In the Cox proportional hazard analysis, treatment response was the only factor associated with survival outcomes. However, PD-1/PD-Ls expression, either in lymphoma or stroma, was not a predictor for survival outcomes. In conclusion, differential PD-1/PD-Ls expressions were observed among various histological PTCL subtypes. In this study, we were unable to demonstrate an association between PD-1/PD-Ls expression, clinical characteristics, treatment response, and outcomes of PTCL patients., (© 2022 S. Karger AG, Basel.)