Magnetic CAR T cell purification using an anti-G4S linker antibody.

Chimeric antigen receptor (CAR) redirected T cells are successfully employed in the combat against several hematological malignancies, however, are often compromised by low transduction rates making refinement of the CAR T cell products necessary. Here, we report a broadly applicable enrichment protocol relying on marking CAR T cells with an anti-glycine4-serine (G4S) linker antibody followed by magnetic activated cell sorting (MACS). The protocol is broadly applicable since the G4S peptide is an integral part of the vast majority of CARs as it links the VH and VL recognition domains. We demonstrate the feasibility by using the canonical second generation CARs specific for CEA and Her2, respectively, obtaining highly purified CAR T cell products in a one-step procedure without impairing cell viability. The protocol is also applicable to a dual specific CAR (tandem CAR). Except for CD39, T cell activation/exhaustion markers were not upregulated after separation. Purified CAR T cells retained their functionality with respect to antigen-specific cytokine secretion, cytotoxicity, and the capacity to proliferate and eliminate cognate tumor cells upon repetitive stimulation. Collectively, the one-step protocol for purifying CAR T cells extends the toolbox for preclinical research and specifically for clinical CAR T cell manufacturing.

Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges.

Chimeric antigen receptor (CAR) T cells are "living drugs" that specifically recognize their target antigen through an antibody-derived binding domain resulting in T cell activation, expansion, and destruction of cognate target cells. The FDA/EMA approval of CAR T cells for the treatment of B cell malignancies established CAR T cell therapy as an emerging pillar of modern immunotherapy. However, nearly every second patient undergoing CAR T cell therapy is suffering from disease relapse within the first two years which is thought to be due to downregulation or loss of the CAR target antigen on cancer cells, along with decreased functional capacities known as T cell exhaustion. Antigen downregulation below CAR activation threshold leaves the T cell silent, rendering CAR T cell therapy ineffective. With the application of CAR T cells for the treatment of a growing number of malignant diseases, particularly solid tumors, there is a need for augmenting CAR sensitivity to target antigen present at low densities on cancer cells. Here, we discuss upcoming strategies and current challenges in designing CARs for recognition of antigen low cancer cells, aiming at augmenting sensitivity and finally therapeutic efficacy while reducing the risk of tumor relapse.

Incidence and predictors of idiopathic pneumonia syndrome in hematopoietic stem cell transplant patients: a nationwide registry study.

Idiopathic pneumonia syndrome (IPS) is a rare but deadly complication of hematopoietic stem cell transplantation (HSCT). This study characterized the incidence and risk factors for IPS after HSCT in Taiwan. Data from January 2009 to February 2019 was collected from the Taiwan Society of BMT national registry. Forty-three (1.1%) of 3924 HSCT patients who developed IPS were identified. Incidence of IPS was lower in patients who received autologous HSCT than patients who received allogeneic HSCT (0.68% vs 1.44%, P = 0.022). Multivariate analysis showed that use of TBI and intravenous busulfan in the conditioning regimen were each independent predictor of IPS after HSCT. In addition, development of IPS was significantly associated with increased risk of death in the first 120 days post-HSCT (HR, 2.09; 95% CI, 1.08 to 4.05, P = 0.029) and 2 years post-HSCT (HR, 1.65; 95% CI, 1.07 to 2.542, P = 0.023), but not beyond 2 years post-HSCT. However, survival outcomes did not differ significantly between patients with IPS who received autologous versus allogeneic HSCT (P = 0.52). In conclusion, despite the relatively low incidence of post-HSCT IPS in Taiwan, mortality remains high. The results of this study will help to identify high-risk patients for early intervention and guide future therapeutic research.

Application of PLASMIC Score in Risk Prediction of Thrombotic Thrombocytopenic Purpura: Real-World Experience From a Tertiary Medical Center in Taiwan.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by severe ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency (activity <10%). Urgent intervention based on the timely evaluation of ADAMTS13 level is crucial to guide optimal therapy. The recently developed PLASMIC score based on seven items allows the rapid identification of patients at high risk for TTP due to severe ADAMTS13 deficiency. This retrospective study included 31 hospitalized patients with suspicious thrombotic microangiopathy in National Cheng Kung University Hospital from December 2016 to July 2021. Data on ADAMTS13 activity and medical and laboratory information were retrieved from medical records. The PLASMIC score could be calculated in 24 of the 31 patients with available data, and the final cohort was stratified according to the 7-point PLASMIC score. All patients with high PLASMIC score (6-7) exhibited severe ADAMTS13 deficiency (activity ≤10%). One patient with a brain tumor and a PLASMIC score of 6 did not have severe ADAMTS13 activity of ≤10%. The patients in the intermediate- and low risk groups (PLASMIC scores of 5 and 0-4, respectively) exhibited ADAMTS13 activities of above 10%. Given the role of prompt diagnosis in the timely delivery of appropriate therapy, these findings confirm and strengthen the predictive value of the PLASMIC score in patients at high risk for TTP due to severe ADAMTS13 deficiency.

Letermovir prophylaxis for cytomegalovirus reactivation in children who underwent hematopoietic stem cell transplantation: A single-institute experience in Taiwan.

From January 2019 to May 2021, 11 children underwent allogeneic stem cell transplantation at our institute. Four of them received letermovir for cytomegalovirus prophylaxis. Three children, none of whom received prophylaxis, experienced cytomegalovirus reactivation. Letermovir is a promising medication for use in cytomegalovirus prophylaxis in children. Further studies are warranted.

Outcome of young adult patients with very-high-risk acute lymphoblastic leukemia treated with pediatric-type chemotherapy - a single institute experience.

BACKGROUND/PURPOSE: Adult patients of acute lymphoblastic leukemia (ALL) with very high-risk (VHR) characteristics have an inferior outcome, and allogeneic hematopoietic stem cell transplantation (HSCT) is usually performed. In contrast, VHR pediatric patients can be treated effectively with minimal residual disease (MRD)-guided pediatric protocols and HSCT are not always needed. METHODS: We retrospectively reviewed young adult ALL VHR patients treated with the pediatric-type (TPOG-ALL-2002 VHR) regimen in our institute from 2008 to 2019 and compared the event-free survival (EFS) with patients treated with an adult-type regimen (Hyper-CVAD alternating with high dose methotrexate and cytarabine). RESULTS: We identified 16 patients treated with the TPOG and 11 treated with the Hyper-CVAD regimen. Philadelphia chromosome-positive (n = 10) and T-cell immunophenotype (n = 11) are the most common VHR features. Compared with the Hyper-CVAD group, patients treated with the TPOG regimen showed a trend toward better EFS with a hazard ratio (HR) of 0.42 (p = 0.16). Compared with untransplanted patients, HSCT showed a positive trend in the Hyper-CVAD (HR 0.22, p = 0.12) but not in the TPOG group (p = 0.37). Untransplanted patients treated initially with the hyper-CVAD regimen had a significantly worse outcome than the TPOG regimen (HR 4.19, p < 0.05). In the TPOG group, patients with negative MRD at the end of consolidation had a significantly better outcome (HR 0.12, p = 0.03). CONCLUSION: Young adult VHR patients can be effectively treated with the TPOG-ALL-2002 protocol, and those who achieved MRD negativity before the end of consolidation have a good outcome without allogeneic HSCT.

Pure Red Cell Aplasia and Other Haematological Diseases Associated With Thymoma: A Case Series and Systematic Review.

Background: Thymoma-associated haematological diseases (HDs), such as pure red cell aplasia (PRCA) and Good's syndrome, are extremely rare, and due to the paucity of large-scale studies, the characteristics, remission after thymectomy, and long-term evaluation remain undetermined. Methods: We retrospectively assessed patients with thymoma and associated HDs from Jan 2005 to Dec 2020. All patients received thymectomy and/or additional treatments for HDs. A comparison with thymoma-associated myasthenic gravis (MG), and a systematic review from PubMed/MEDLINE and Embase were conducted. Results: In the median follow-up of 56 months, 130 patients were enrolled. Patients with thymoma-associated MG (n = 46) and HDs [n = 8; PRCA (n = 5), PRCA and Good's syndrome (n = 2) and autoimmune haemolytic anaemia (n = 1)] were evaluated. Patients with MG had a significantly higher remission rate after thymectomy (50 vs. 17%; p = 0.0378) as compared to those with other autoimmune diseases. Two of seven patients with PRCA experienced remission with thymectomy alone, and an additional two patients achieved remission with thymectomy plus immunosuppressive therapy (IST). In the systematic review, 60 studies (case reports, n = 46; case series including the present study, n = 14) were evaluated. Forty-four percent of patients were diagnosed with PRCA after thymoma, and 61% achieved remission with thymectomy plus IST; however, Good's syndrome was unaffected. Conclusions: Our study indicates that patients with thymoma-associated autoimmune diseases other than MG have a lower remission rate than those with MG. Remission of thymoma-associated PRCA can be achieved by thymectomy and IST. This study provides insight into extremely rare but puzzling autoimmune manifestations.

Validation of a Post-Transplant Lymphoproliferative Disorder Risk Prediction Score and Derivation of a New Prediction Score Using a National Bone Marrow Transplant Registry Database.

BACKGROUND: We externally validated Fujimoto's post-transplant lymphoproliferative disorder (PTLD) scoring system for risk prediction by using the Taiwan Blood and Marrow Transplant Registry Database (TBMTRD) and aimed to create a superior scoring system using machine learning methods. MATERIALS AND METHODS: Consecutive allogeneic hematopoietic cell transplant (HCT) recipients registered in the TBMTRD from 2009 to 2018 were included in this study. The Fujimoto PTLD score was calculated for each patient. The machine learning algorithm, least absolute shrinkage and selection operator (LASSO), was used to construct a new score system, which was validated using the fivefold cross-validation method. RESULTS: We identified 2,148 allogeneic HCT recipients, of which 57 (2.65%) developed PTLD in the TBMTRD. In this population, the probabilities for PTLD development by Fujimoto score at 5 years for patients in the low-, intermediate-, high-, and very-high-risk groups were 1.15%, 3.06%, 4.09%, and 8.97%, respectively. The score model had acceptable discrimination with a C-statistic of 0.65 and a near-perfect moderate calibration curve (HL test p = .81). Using LASSO regression analysis, a four-risk group model was constructed, and the new model showed better discrimination in the validation cohort when compared with The Fujimoto PTLD score (C-statistic: 0.75 vs. 0.65). CONCLUSION: Our study demonstrated a more comprehensive model when compared with Fujimoto's PTLD scoring system, which included additional predictors identified through machine learning that may have enhanced discrimination. The widespread use of this promising tool for risk stratification of patients receiving HCT allows identification of high-risk patients that may benefit from preemptive treatment for PTLD. IMPLICATIONS FOR PRACTICE: This study validated the Fujimoto score for the prediction of post-transplant lymphoproliferative disorder (PTLD) development following hematopoietic cell transplant (HCT) in an external, independent, and nationally representative population. This study also developed a more comprehensive model with enhanced discrimination for better risk stratification of patients receiving HCT, potentially changing clinical managements in certain risk groups. Previously unreported risk factors associated with the development of PTLD after HCT were identified using the machine learning algorithm, least absolute shrinkage and selection operator, including pre-HCT medical history of mechanical ventilation and the chemotherapy agents used in conditioning regimen.

Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial.

BACKGROUND: Due to increasing use of frontline lenalidomide, effective and safe lenalidomide-free therapies for relapsed/refractory multiple myeloma (RRMM) are needed in Asia. This subgroup analysis of phase 3 CANDOR study evaluated efficacy and safety of KdD vs Kd in Asian patients with RRMM. METHODS: Self-identified Asian patients with RRMM (KdD = 46; Kd = 20) with 1‒3 prior therapies were included. The primary endpoint of progression-free survival was estimated by stratified Cox regression. RESULTS: Baseline demographics and patient characteristics were balanced in both arms. KdD reduced the risk of progression or death by 25% vs Kd [hazard ratio (HR) = 0.75; 95% CI 0.259, 2.168] in the Asian subgroup, compared with 37% vs Kd (0.63; 0.464, 0.854) in the overall CANDOR population. Percentage of patients who reported grade ≥ 3 treatment-emergent adverse events (TEAEs) in the KdD and Kd arms was 95.7 and 90.0%, respectively. Serious AEs were observed in 58.7 and 40.0% of patients in the KdD and Kd arms, respectively. There were two (4.3%) fatal TEAEs in the KdD arm due to infections. CONCLUSIONS: There was a trend toward better efficacy and a favorable benefit-risk profile for KdD vs Kd in Asian patients with RRMM. Cautious interpretation is warranted due to small patient size.

Subtle cardiac dysfunction in lymphoma patients receiving low to moderate dose chemotherapy.

Left ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04-9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.

Charlson comorbidity index predicts outcomes of elderly after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND/PURPOSE: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but advanced age with multiple comorbidities limits the eligibility for allo-HSCT. We conducted a retrospective study to investigate the comorbidities assessments and prognostic factors that predict outcomes for these patients. METHODS: Clinical data of patients older than 50 years who had received diagnoses of AML or MDS and underwent allo-HSCT were obtained. Information on patient characteristics, including age, gender, allogeneic transplant type, conditioning regimens, Charlson comorbidity index (CCI), and presence of acute graft-versus-host disease (GVHD) or chronic GVHD, were collected and analyzed. RESULTS: Two hundred fifty-five elderly patients with a median age at allo-HSCT of 57 years were included. The significant prognostic factors associated with worse overall survival (OS) were CCI ≥3 (hazard ratio: 1.88) and grade III-IV acute GVHD (3.18). Similar findings were noted in the non-relapse mortality analysis. To investigate the effects of chronic GVHD on patient outcomes, OS analysis was performed for those with survival >100 days after transplantation. The results revealed CCI ≥3 (1.88) and grade III-IV acute GVHD (2.73) remained poor prognostic factors for OS, whereas mild chronic GVHD (0.43) was associated with better OS. CONCLUSION: This cohort study suggests that CCI ≥3 predicts poor outcomes, primarily due to a higher NRM risk. Careful management of GVHD after transplantation could improve outcomes in elderly patients with AML or MDS after allo-HSCT.

Lenalidomide with dexamethasone to multiple myeloma patients relapsing from bortezomib-based induction therapies: A prospective, observational study.

Lenalidomide with dexamethasone (Len/Dex) is considered to be an effective and well-tolerated regimen to treat multiple myeloma (MM) patients relapsing after bortezomib induction therapy. With the increase in novel agents targeting refractory and relapsed MM, the identification of clinical or laboratory variables that can predict the appropriate candidates of Len/Dex is essential. To address this question, we prospectively assessed 38 adult MM patients who received bortezomib-based induction therapy and were administered Len/Dex for their first relapse. These 38 patients were stratified into the symptomatic relapse group (n = 10) and biological relapse group (n = 28) according to the disease status when Len/Dex was initiated. The overall response rate in the symptomatic group and biological relapse group was 70.0% (7/10) and 60.7% (17/28), respectively (P = 0.964). These two groups harbored a comparable median Len/Dex treatment duration (139 vs. 225 days; P = 0.876) and progression-free survival 2 (PFS2) (501 vs. 1289 days; P = 0.410). Multivariate analyses failed to show that treating biological relapse (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 0.43-3.88; P = 0.648), PFS with bortezomib-based induction therapies ≥18 months (HR: 1.79; 95% CI: 0.64-5.01; P = 0.266), autologous hematopoietic stem cell transplantation (HR: 2.18; 95% CI: 0.56-8.55; P = 0.262), and high-risk cytogenetics (HR: 0.85; 95% CI: 0.18-3.93; P = 0.835) were attributed to depth of Len/Dex treatment. In conclusion, whether MM patients treated by Len/Dex for biological relapse would have a better outcome than those prescribed for symptomatic relapse remains inconclusive. Treating significant biological relapse and symptomatic relapse remains the current consensus.

Maternal survival of patients with pregnancy-associated cancers in Taiwan - A national population-based study.

Pregnancy-associated cancer (PAC), defined as cancers diagnosed during pregnancy or the first year after delivery, affects one to two in every 1000 pregnancies. Although PAC is expected to be a growing issue, information about PAC in the Asian population is still scarce. Women with cancer diagnosed at the age of 16-49 years between 2001 and 2015 were selected from the Taiwan Cancer Registry and linked with the National Birth Reporting Database to identify PAC patients. We compared the overall survival of patients with PAC to patients without pregnancy. Among 126,646 female cancer patients of childbearing age, 512 were diagnosed during pregnancy, and 2151 during the first postpartum year. Breast cancer was the most common PAC (N = 755, 28%). Compared with patients without pregnancy in the control group, patients with cancers diagnosed during pregnancy and the first postpartum year generally had more advanced stages (odds ratio 1.35 and 1.36, 95% confidence interval [CI] 1.02-1.77 and 1.18-1.57, respectively). For all cancer types combined and controlled for the stage, age, and year of diagnosis, patients with PAC had similar overall survival with those in the control group, with a hazard ratio (HR) of 1.07 (95% CI 0.80-1.41) for the pregnancy group and HR 1.02 (95% CI 0.88-1.18) for the postpartum group. The diagnosis of breast cancer during the first postpartum year was linked with shorter survival (HR 1.34, 95% CI 1.05-1.72). In contrast, patients with postpartum lymphoma (HR 0.11, 95% CI 0.02-0.79) and cervical cancer (HR 0.40, 95% CI 0.20-0.82) had better prognosis. In general, the diagnosis of cancer during pregnancy or the first postpartum year does not affect the survival of patients with most cancer types. Exceptions include the worse prognosis of postpartum breast cancer and the better outcome of postpartum lymphoma and cervical cancer.

Cost-utility analysis of inotuzumab ozogamicin for relapsed or refractory B cell acute lymphoblastic leukemia from the perspective of Taiwan's health care system.

OBJECTIVES: We conduct a cost-utility analysis of inotuzumab ozogamicin (INO) versus chemotherapy as the standard of care (SOC) for adults with relapsed or refractory B cell acute lymphoblastic leukemia. METHODS: A Markov model incorporating transition probabilities between health states was applied to simulate disease progression. The model inputs, including overall survival, progression-free survival, and utility parameters, were obtained from the INO-VATE ALL trial and literatures. The Taiwan Cancer Registry Database and the Health and Welfare Database were utilized to identify the patient cohort and medical costs from the perspective of National Health Insurance Administration. The lifetime medical costs (in 2017 US dollars), quality-adjusted life years (QALYs) gained, and associated incremental cost-effectiveness ratio (ICER) were the main study outcomes. RESULTS: The lifetime medical costs for INO and SOC were $176,795 and $69,496, and the QALYs gained were 2.25 and 0.84, respectively. The ICER for INO versus SOC was $76,044 per QALY gained, which is slightly more than three times Taiwan's gross domestic product per capita (i.e., $73,224). Favorable economic results for INO versus SOC were found with an increased time horizon for model simulation, less discounting for the future benefit, and higher stem cell transplantation (SCT) rate after INO treatment; and among patients aged less than 55 years, with no SCT history, or in the first salvage treatment. CONCLUSIONS: INO versus SOC has higher costs but is more effective. The use of INO is favorable for patients in the early treatment course and when more future benefit associated with INO is considered.

Angioimmunoblastic T-cell lymphoma in Taiwan reveals worse progression-free survival for RHOA G17V mutated subtype.

Angioimmunoblastic T-cell lymphoma (AITL) carries genetic mutations of TET2, RHOA, and IDH2, but the prognostic impact of these mutations is not widely investigated. Although one study shows no difference in overall survival between patients with or without RHOA G17V mutation, a poor performance status is associated with RHOA G17V-mutated AITL, which is an independent adverse factor. We retrospectively investigated the prognostic impact of RHOA G17V mutation in AITL patients. A total of 31 cases were enrolled (male-to-female, 2.1; mean age: 62.8 years). RHOA G17V mutation was analyzed by deep sequencing. We found that in contrast to RHOA-wild type, patients with RHOA G17V-mutated AITL more frequently had B symptoms (p = .035), stronger PD1 expression (p = .045), ≥3 TFH markers (p = .011), higher blood vessel density (p<.001), and poorer progression-free survival (p = .046). These results support a role for RHOA genetic testing in AITL patients as ROHA G17V mutation carries a worse prognosis, probably associated with B symptoms and stage IV disease.

The incidence and risk factors of hepatic veno-occlusive disease after hematopoietic stem cell transplantation in Taiwan.

Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD. The cumulative incidence of hepatic VOD in the whole cohort of 2345 patients was 1.66%. In multivariate analysis, disease diagnosis of myelodysplastic syndrome, chronic HCV infection, condition regimens of bulsulfan intravenously administered, and antithymocyte immunoglobulin were independent factors to predict higher risk of hepatic VOD. The overall mortality rate for patients with hepatic VOD was 79%. Patients with hepatic VOD had significant worse survival outcomes when compared with those without hepatic VOD (P = 0.00063). In conclusion, although the incidence is low, hepatic VOD remains a serious complication after HSCT in Taiwan. The findings of this study could be the basis for developing prophylactic or early treatment strategies for hepatic VOD.

Autologous stem cell transplantation in multiple myeloma: Post-transplant outcomes of Taiwan Blood and Marrow Transplantation Registry.

BACKGROUND/PURPOSE: Multiple myeloma (MM) is a monoclonal plasma cell malignancy. The primary choice of treatment for MM is induction therapy followed by autologous stem cell transplantation (ASCT). This study aimed to analyze the treatment efficacy of ASCT in a Taiwanese cohort and evaluate possible prognostic factors. METHODS: From the database of the Taiwan Blood and Marrow Transplantation registry, data on 396 patients with MM who underwent ASCT were reviewed. RESULTS: The average age of participants was 54.8 years, and there were more men than women (57.6% vs. 42.4%). Most patients were diagnosed with IgG-type myeloma (52.4%), followed by IgA-type (23.2%) and light-chain type (21.4%). Patients with Durie Salmon Staging System (DSS) III disease accounted for 61.9% of the study cohort, while 23.7% had stage II and 14.4% had stage I disease. The median progression-free survival (PFS) and overall survival (OS) after ASCT were 46.5 months and 70.4 months, respectively. DSS III was a poor prognostic factor affecting both PFS and OS with a duration of 35.9 months and 69.0 months, respectively, compared with the other two stages (p = 0.006 and p = 0.03, respectively). In addition, patients with better treatment response before ASCT had better PFS and OS compared with those who did not show a response (both p < 0.0001). The overall incidence of organ toxicities associated with transplantation was low. CONCLUSION: In conclusion, our cohort showed that myeloma patients with early DSS and better treatment response before ASCT had better long-term survival outcomes.

Incidence and treatment outcome of aplastic anemia in Taiwan-real-world data from single-institute experience and a nationwide population-based database.

Aplastic anemia (AA) is a rare disease characterized by pancytopenia and bone marrow failure. The incidence of AA tends to be higher in Asia than in the West, but real-world data about AA in Asia remain limited. We aimed to describe the basic data, treatment, and outcome of AA patients from our institute and evaluate the incidence of AA in Taiwan with a nationwide population-based cohort from National Health Insurance Research Database (NHIRD). We identified patients older than 2 years with AA in the Registry of Catastrophic Illness of NHIRD between 2001 and 2010 and excluded patients with any diagnosis suggestive of congenital or secondary bone marrow failure. With a total of 1270 patients, the overall incidence was 5.67 per million people per year, and there was a biphasic age distribution of incidence rate, highest in ≥ 70 years (19.83 per million people per year) and another peak at age 2-9 years (5.26 per million people per year). Overall, the 5-year survival was 60.0%. Hematopoietic stem cell transplantation (HSCT) and anti-thymocyte globulin-based immunosuppressive therapy (IST) were the major first-line treatments in patients younger than 40 years and were linked with good survival. In contrast, the majority of patients older than 60 years were treated with androgen, and the survival was poor. In multivariate analysis, "severe AA," "very severe AA," and "treatment other than HSCT, IST, or androgen" were independent risk factors for inferior survival. In conclusion, the incidence of AA in Taiwan is consistent with nearby Asian countries and is higher than in the West. Advanced age is associated with higher incidence and poorer outcome.

Stem cell transplantation for T-cell lymphomas in Taiwan.

T-cell lymphomas are generally aggressive malignancies with poor prognosis. There are no standard treatment guidelines for T-cell lymphomas, and the timing of stem cell transplantation (SCT) is not well known. In this study, we investigated the outcomes of Taiwanese patients with T-cell lymphomas after SCT. We retrospectively analyzed 131 patients with T-cell lymphomas receiving SCT (autologous: 90, allogeneic: 41) from 2009 to 2014. More autologous SCT recipients were ALCL or in complete remission, and more allogeneic recipients had advanced disease. 56 patients who were sensitive to chemotherapy underwent SCT as upfront setting. The 2-year PFS and OS rates were 67.0 and 64.5%, respectively. Regarding disease status before transplantation, patients with CR1 had the best outcomes. Among different subtypes, patients with natural killer/T-cell lymphomas showed the worst outcomes, with 2-year OS rate of 23.5%. The OS rates for the other three major subtypes were as follows: 72.9% for ALCL; 75.0% for AITL; and 51.4% for PTCL-NOS. For more rare subtypes, such as ATLL and SPTCL, data from our study show that SCT can be beneficial. We concluded that upfront autologous SCT is feasible and effective for patients with low PIT, and disease status at transplant is the strong predictor of outcome.