New presentations and exacerbations of immune thrombocytopenia after coronavirus disease 2019 vaccinations: the Taiwan experience.

Immune thrombocytopenia (ITP) is a condition that is distinct from thrombosis with thrombocytopenia syndrome (TTS) that may also occur after coronavirus disease 2019 (COVID-19) vaccinations. Previous reports revealed an increased ITP incidence after ChAdOx1, a vaccine for COVID-19. Our study aimed to highlight the key features of ITP after COVID-19 vaccination. From April to October 2021, we collected data on 23 patients, including nine men and 14 women, with ITP from five hospitals across Taiwan who received either the ChAdOx1 or mRNA-1273 vaccine before development or exacerbation of ITP. Our findings revealed that both ChAdOx1 and mRNA-1273 vaccines were associated with ITP. Many patients responded well to steroids and immune suppressants, which may also suggest that the nature of thrombocytopenia is more like ITP rather than TTS. Lack of thrombosis, low D-dimer level, and negative anti-PF4 result could help to exclude TTS, which is also a rare but a far more lethal condition.

Dual-lumen power injectable peripherally inserted central catheters in allogeneic hematopoietic stem cell transplantation: A prospective observational study.

AIMS AND OBJECTIVES: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring. BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments. DESIGN: A prospective observational study was conducted according to the STROBE guidelines. METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT. RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]). CONCLUSION: The power injectable PICC is a feasible venous access device for allo-HSCT. RELEVANCE TO CLINICAL PRACTICE: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.

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.

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia - A systematic review and meta-analysis.

BACKGROUND AND AIMS: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. METHODS AND RESULTS: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included. CONCLUSION: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. REGISTRATION NUMBER: PROSPERO(CRD42018091657).

Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia.

Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as the HOX family have been well characterized in acute myeloid leukemia (AML), the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo AML patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation. Patients with higher HOPX expression had a lower complete remission rate and shorter survival. The finding was validated in two independent cohorts. Multivariate analysis revealed that higher HOPX expression was an independent unfavorable prognostic factor irrespective of other known prognostic parameters and gene signatures derived from multiple cohorts. Gene set enrichment analysis showed higher HOPX expression was associated with both hematopoietic and leukemia stem cell signatures. While HOPX and HOX family genes showed concordant expression patterns in normal hematopoietic stem/progenitor cells, their expression patterns and associated clinical and biological features were distinctive in AML settings, demonstrating HOPX to be a unique homeobox gene. Therefore, HOPX is a distinctive homeobox gene with characteristic clinical and biological implications and its expression is a powerful predictor of prognosis in AML patients.

Development of 1-Amino-4-(phenylamino)anthraquinone-2-sulfonate Sodium Derivatives as a New Class of Inhibitors of RANKL-Induced Osteoclastogenesis.

A series of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium derivatives was synthesized and evaluated for osteoclast inhibition using a TRAP-staining assay. Among them, two compounds, LCCY-13 and LCCY-15, dose-dependently suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Moreover, the cytotoxicity assay on RAW264.7 cells suggested that the inhibition of osteoclastic bone resorption by these compounds was not a result of their cytotoxicity. Further, the inhibitory activities of compounds LCCY-13 and LCCY-15 were further confirmed by including specific inhibition of NFATc1 expression levels in nuclei using an immunofluorescent analysis. In addition, LCCY-13 and LCCY-15 also significantly attenuated the bone resorption activity of osteoclasts according to a pit formation assay. Thus, a new class of 1-amino-4-(phenylamino)anthraquinone-2-sulfonate sodium compounds might be considered as an essential lead structure for the further development of anti-resorptive agents.

Novel inhibitors of RANKL-induced osteoclastogenesis: Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones.

A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced osteoclastogenesis-related marker genes, such as NFATc1, c-fos, TRAP, and cathepsin K. Notably, 3d could significantly attenuate the bone-resorbing activity of osteoclasts in the pit formation assay. Thus, this study might provide a new class of lead structures that warrant further development as potential anti-resorptive agents.

NSC746364, a G-quadruplex-stabilizing agent, suppresses cell growth of A549 human lung cancer cells through activation of the ATR/Chk1-dependent pathway.

The telomere is considered to be a potential target for cancer therapy. NSC746364, a novel G-quadruplex-stabilizing agent, has been found to have cytotoxic effects on various cancer cells. To date, its pharmacological mechanisms are still unknown. The goal of this study was to investigate the molecular mechanisms of NSC746364 on the A549 human lung adenocarcinoma cell line. For this, we used a wide variety of in vitro assays. The intracellular signaling pathways including DNA damage sensing and response proteins, cell cycle regulatory proteins, and some key executors involved in apoptosis were evaluated in this study. Our study suggested that NSC746364 induced cell cycle arrest at the G2/M phase and triggers programming cell death on A549 human lung cancer cells, whose effects are modulated through the activation of the ATR/Chk1 pathway, the downregulation of cyclin B1 expression, and the activation of caspase-3. Consequently, our results indicated that NSC746364 may have therapeutic potential as a chemotherapy for non-small-cell lung cancers.

Haploidentical and matched unrelated donor allogeneic hematopoietic stem cell transplantation offer similar survival outcomes for acute leukemia.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has emerged as an effective approach for acute leukemia, primarily due to the inherent difficulty in finding human leukocyte antigen-matched unrelated donors (MUD). Nevertheless, it remains uncertain whether haplo-HSCT and MUD-HSCT can provide comparable outcomes in patients with acute leukemia. AIMS: This study aimed to assess the overall survival (OS) and leukemia-free survival (LFS) outcomes between the MUD-HSCT and haplo-HSCT groups. METHODS AND RESULTS: This retrospective analysis encompassed adult patients with acute leukemia undergoing the initial allo-HSCT. Among these 85 patients, we stratified 33 patients into the MUD-HSCT group and 52 to the haplo-HSCT group. The primary outcomes were OS and LFS. The median OS was not reached in the haplo-HSCT group, while it reached 29.8 months in patients undergoing MUD-HSCT (p = .211). Likewise, the median LFS periods were 52.6 months in the haplo-HSCT group and 12.7 months in the MUD-HSCT group (p = .212). Importantly, neither the OS nor LFS showed substantial differences between the MUD-HSCT and haplo-HSCT groups. Furthermore, univariate analyses revealed that haplo-HSCT did not demonstrate a significantly higher risk of worse LFS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.38-1.25; p = .216) or OS (HR, 0.67; 95% CI, 0.36-1.26; p = .214) than MUD-HSCT. Notably, a high European Group for Blood and Marrow Transplantation risk score (HR, 1.44; 95% CI, 1.10-1.87; p = .007) and non-complete remission (HR, 2.48; 95% CI, 1.17-5.23; p = .017) were significantly correlated with worse OS. CONCLUSION: Haplo-HSCT may serve as an alternative to MUD-HSCT for the treatment of acute leukemia, offering similar survival outcomes.

The efficacy and tolerability of bortezomib, thalidomide, and dexamethasone induction therapy with a thalidomide dose step-up strategy in patients with newly diagnosed multiple myeloma: A prospective observational study.

BACKGROUND: Thalidomide-containing regimens cause adverse events (AEs) that may require a reduction in treatment intensity or even treatment discontinuation in patients with multiple myeloma. As thalidomide toxicity is dose-dependent, identifying the most appropriate dose for each patient is essential. AIMS: This study aimed to investigate the effects of a thalidomide dose step-up strategy on treatment response and progression-free survival (PFS). METHODS AND RESULTS: This prospective observational study included 93 patients with newly diagnosed multiple myeloma (NDMM) who received bortezomib, thalidomide, and dexamethasone (VTD). The present study assessed the incidence of thalidomide dose reduction and discontinuation, the overall dose intensity, and their effects on therapeutic efficacy. Furthermore, this study used Cox proportional hazard models to analyze the factors contributing to thalidomide intolerability. The results showed the overall response rates in all patients and the evaluable patients were 78.5% and 98.7%, respectively. The median PFS in the study cohort was not reached. The most common thalidomide-related AEs were constipation (32.3%) and skin rash (23.7%), resulting in dose reduction and discontinuation rates of 22.6% and 21.5%, respectively. The responders had a significantly higher average thalidomide dose intensity than the nonresponders (88.6% vs. 42.9%, p < .001). CONCLUSION: The thalidomide dose step-up approach is a viable option for patients with NDMM receiving VTD induction therapy with satisfactory efficacy and tolerability. However, thalidomide intolerance may lead to dose reduction or discontinuation due to unpredictable AEs, leading to lower dose intensity and potentially inferior treatment outcomes. In addition to a dose step-up strategy, optimal supportive care is critical for patients with multiple myeloma receiving VTD induction therapy.

Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA topoisomerase I inhibitory properties.

A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50=1.66 µM) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs.

Clinical Features and Outcomes of Primary Breast Diffuse Large B-Cell Lymphoma: A Matched-Pair Study.

Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.

Synthesis, telomerase evaluation and anti-proliferative studies on various series of diaminoanthraquinone-linked aminoacyl residue derivatives.

Four series of compounds containing an anthraquinone-linked moiety and symmetrical or asymmetrical aminoacyl residues in side chains at positions 1,4-, 1,5-, 2,6-, and 2,7- were synthesized and evaluated for their inhibitory effects toward telomerase and hTERT expression. Of these, only compound B11 showed selective inhibition of telomerase activity. Although it is not as competent as several of the anthraquinones we identified previously, nevertheless, the result is consistent with that the general structure moiety at the 1,5-position of diaminoanthraquinone-linked compound is important for the telomerase inhibitory activity. Interestingly, compounds A6, A8, C8, and D8 exhibited selective repressing activities toward hTERT expression and showed less effect toward proliferation of the treated cancer cells. Although it is not apparent which structure moiety is responsible for the telomerase repression effects of these compounds, they could be further developed as potential anti-tumor agents.

Clinical Features and Immunophenotypes of Double-Hit Diffuse Large B-Cell Lymphoma.

Double-hit (DH) genetics induces a reduction in the complete remission (CR) and, consequently, in poor overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Unfortunately, DH identification is time-consuming. Here, we retrospectively reviewed 92 newly diagnosed DLBCL patients, stratified them into the DH (n = 14) and non-DH groups (n = 78), and compared their clinical features and outcomes. The results revealed that the DH group had a higher percentage of bulky disease than the non-DH group (64.3% vs. 28.2%; p = 0.013). More patients in the DH group tested positive for double expresser (DE) (50.0% vs. 21.8%; p = 0.044). The three-year OS rates of patients with and without DH were 33.3% and 52.2%, respectively (p = 0.016). Importantly, advance stage and multiple comorbidities were correlated with a high mortality rate in multivariate analysis. Furthermore, by combining DE and the bulky disease, a specificity of 89.7% for DH prediction was achieved. In summary, DH genetics, not DE immunopositivity, could be a factor for an inferior OS in DLBCL. A combination of bulky disease and a positive DE immunophenotype could facilitate DH genetics prediction in newly diagnosed DLBCL patients.

Acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation: a retrospective study from a single institution.

OBJECTIVE: The outcomes of patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are poor. However, the risk factors for relapse in this context remain unclear. METHODS: We retrospectively assessed 84 consecutive adult AML patients who underwent allo-HSCT and achieved complete remission (CR). These patients were dichotomized into non-relapse (n = 58) and relapse (n = 26) groups, and the cumulative relapse rates and associated risk factors were examined. We also examined the treatments for and outcomes of patients with AML relapse after allo-HSCT. RESULTS: Non-CR status before allo-HSCT and high-risk cytogenetics were significant risk factors for AML relapse in univariate analysis, and non-CR status was also identified as a risk factor in multivariate analysis. The cumulative AML relapse rates after allo-HSCT were significantly higher in patients with non-CR (70.0%) compared with patients with CR (25.6%). Only 2 of the 26 relapsed patients remained alive on the study-censored day. CONCLUSIONS: Non-CR status before allo-HSCT was a significant risk factor for AML relapse after allo-HSCT. Patients with AML relapse after allo-HSCT had poor outcomes due to a lack of response to salvage remission-induction chemotherapy or treatment-related adverse events.

Oncogenesis induced by combined Phf6 and Idh2 mutations through increased oncometabolites and impaired DNA repair.

The pathogenesis of acute leukemia involves interaction among genetic alterations. Mutations of IDH1/2 and PHF6 are common and co-exist in some patients of hematopoietic malignancies, but their cooperative effects remain unexplored. In this study, we addressed the question by characterizing the hematopoietic phenotypes of mice harboring neither, Phf6 knockout, Idh2 R172K, or combined mutations. We found that the combined Phf6KOIdh2R172K mice showed biased hematopoietic differentiation toward myeloid lineages and reduced long-term hematopoietic stem cells. They rapidly developed neoplasms of myeloid and lymphoid lineages, with much shorter survival compared with single mutated and wild-type mice. The marrow and spleen cells of the combined mutated mice produced a drastically increased amount of 2-hydroxyglutarate compared with mice harboring Idh2 R172K. Single-cell RNA sequencing revealed distinct patterns of transcriptome of the hematopoietic stem/progenitor cells from the combined mutated mice, including aberrant expression of metabolic enzymes, increased expression of several oncogenes, and impairment of DNA repairs, as confirmed by the enhanced γH2AX expression in the marrow and spleen cells. We conclude that Idh2 and Phf6 mutations are synergistic in leukemogenesis, at least through overproduction of 2-hydroxyglutarate and impairment of DNA repairs.

Chemotherapy for Metastatic Gastric Cancer: Does Age Matter? A Single-Center, Retrospective, Real-World Study.

Background: Palliative chemotherapy is the preferred standard of care for patients with metastatic gastric cancer (mGC). It remains uncertain whether older patients with mGC would benefit from palliative chemotherapy. This study aimed to investigate the clinical impact of palliative chemotherapy in older patients with mGC. Methods: This single-institute, retrospective, and real-world study included 428 patients with mGC between January 2009 and December 2019. Among them, 306 who received palliative chemotherapy were further stratified into 2 groups according to age: ≤70 (n = 236) and >70 (n = 70) years. The clinical demographics, outcomes, and hematologic toxicities of chemotherapy were compared between the 2 groups. Prognostic factors were determined using the Cox proportional hazards model. Results: Of the screened 428 patients, older patients had worse overall survival (OS) than younger patients. Among patients who received chemotherapy (n = 306), patients aged >70 and ⩽70 years had comparable progression-free survival (PFS) and OS. The incidence of severe hematologic toxicity was similar between the 2 groups. The Eastern Cooperative Oncology Group performance status of 2 or more metastatic sites, elevated carbohydrate antigen 19-9 level, high neutrophil-to-lymphocyte ratio (NLR), and undergoing palliative gastrectomy were independent prognostic factors for OS. Notably, age >70 years was not a significant factor for poor OS. Conclusions: Older age of >70 years might not be considered an obstacle to administering palliative chemotherapy to patients with mGC.

NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). However, the real-world evidence of nilotinib in newly diagnosed untreated Ph+ CML-CP is limited in Taiwan. The NOVEL-1st study was a non-interventional, multi-center study collecting long-term safety and effectiveness data in patients with newly diagnosed and untreated Ph+ CML-CP receiving nilotinib. We enrolled 129 patients from 11 hospitals. Overall, 1,466 adverse events (AEs) were reported; among these, 151 were serious and 524 were nilotinib-related. Common hematological AEs were thrombocytopenia (31.0%), anemia (20.9%), and leukopenia (14.0%); common nilotinib-related AEs were thrombocytopenia (29.5%), anemia (14.7%), and leukopenia (12.4%). Early molecular response, defined as BCR-ABL ≤ 10% at Month 3, was seen in 87.6% of patients. By 36 months, the cumulative rates of complete hematologic response, complete cytogenetic response, major molecular response, molecular response 4.0-log reduction, and molecular response 4.5-log reduction were 98.5, 92.5, 85.8, 65.0, and 45.0%, respectively. Nilotinib is effective and well-tolerated in patients with newly diagnosed Ph+ CML-CP in the real-world setting. Long-term holistic care and a highly tolerable AE profile may contribute to good treatment outcomes in Ph+ CML-CP under first-line treatment with nilotinib.