Complete Remission Rate Research Articles

PTBP1 is a potential indicator of disease progression in acute myeloid leukemia.

This study aimed to verify a novel potential indicator of disease progression in acute myeloid leukemia (AML) patients. Bone marrow samples were collected from 27 AML patients and 27 controls without hematological malignancies. Polypyrimidine tract-binding protein 1 (PTBP1) expression in bone marrow samples was measured, and the association of PTBP1 with the French-American-British (FAB) classification, cytogenetics, risk stratification, and complete remission (CR) rate was analyzed. The correlation between PTBP1 and Ki-67/p53 expression in AML patients was ultimately evaluated. The results showed that PTBP1 mRNA and protein levels were greater in AML patients than in controls. PTBP1 expression was able to distinguish between AML patients and controls (area under the curve, 0.8601; 95% confidence interval, 0.7632-0.9570). Furthermore, PTBP1 expression was associated with an increased frequency of internal tandem duplication mutations within FMS-like tyrosine kinase-3 (FLT3) and a complex karyotype, while PTBP1 expression was not correlated with FAB classification, monosomal karyotype, isolated biallelic CCAAT/enhancer-binding protein α (CEBPA) mutation, or nucleophosmin 1 (NPM1) mutation in patients with AML. Moreover, PTBP1 expression was associated with a poorer prognosis according to risk stratification and a lower CR rate in AML patients. In addition, PTBP1 expression was positively correlated with the expression of the proliferation marker Ki-67 and negatively correlated with the expression of the apoptosis marker p53 in AML patients. Overall, PTBP1 is a viable biomarker that contributes to the risk prediction and the determination of potential drug targets for AML.

Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Delineation of features, responses, outcomes, and prognostic factors in pediatric PDGFRB-positive acute lymphoblastic leukemia patients: A retrospective multicenter study.

PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p<.05). Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).

Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with KMT2A-rearranged (KMT2Ar) acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) KMT2Ar acute leukemia. AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R KMT2Ar acute leukemia or with AML and nucleophosmin 1 (NPM1) mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m2 if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all KMT2Ar treated patients; efficacy was assessed in those with centrally confirmed KMT2Ar. The separate NPM1 cohort of the trial is ongoing. From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% (P = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease. Revumenib led to high remission rates with a predictable safety profile in R/R KMT2Ar acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.

The clinical implications of BCOR mutations in a large cohort of acute myeloid leukemia patients: a 5-year single-center retrospective study

To elucidate the effect of BCOR mutation (BCOR mut) on clinical outcomes, we included a total of 899 consecutive AML patients in a single-center during July 2016 to December 2021. Fifty cases (5.6%) had BCOR mutations, which co-occurred with mutations of RUNX1, DNMT3A, IDH2, BCORL1, STAG2, SF3B1 and U2AF1, but were exclusive with KIT and CEBPA mutations. BCOR mut was also found to be exclusive with t(8;21)(q22;q22.1) AML in all patients and MLL rearrangements in the European Leukemia Net (ELN) adverse group. In those receiving intensive chemotherapy regimens, BCOR mut was associated with lower complete remission (CR) rates and worse prognosis. Subgroup analysis showed that BCOR mut mainly conferred a poor prognosis in the intermediate and adverse groups of the ELN2017 risk. These results suggest that BCOR mutation is an independent prognostic parameter in AML, implying BCOR mutation as a novel marker for chemorefractory disease and inferior prognosis.

Patients with TP53-Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study.

TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. This study was a single-center, retrospective cohort analysis. Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients.

Evidence based treatment for lupus nephritis: present perspectives and challenges.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease known for its high heterogeneity among individuals, which affects various organs including the kidneys. Lupus nephritis (LN) is a frequent and life-threatening manifestation of the disease, with up to 50% of patients developing kidney involvement. Classification of renal involvement in lupus is based on specific histopathological findings, guiding therapeutical decisions. Immunosuppressive therapy, particularly glucocorticoids combined with cyclophosphamide or mycophenolate mofetil, has been the mainstay of treatment for many years, while rates of complete remission have not changed dramatically. Despite advancements in therapy, in an important proportion of patients LN leads to end-stage kidney disease (ESKD). Emerging therapies including belimumab, voclosporin, and obinutuzumab offer promising results in improving renal outcomes, especially in refractory or relapsing disease. Maintenance therapy is crucial to prevent disease flares and preserve renal function. Supportive measures including lifestyle modifications and non-immunosuppressive pharmacological interventions are nowadays also essential in managing LN. This review emphasizes recent advances of therapy and challenges regarding treatment optimization with strategies to improve long-term outcomes.

Prediction of Response to FDA-Approved Targeted Therapy and Immunotherapy in Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) represents the predominant cancer in pediatric populations, though its occurrence in adults is relatively rare. Pre-treatment risk stratification is crucial for predicting prognosis. Important factors for assessment include patient age, white blood cell (WBC) count at diagnosis, extramedullary involvement, immunophenotype, and cytogenetic aberrations. Minimal residual disease (MRD), primarily assessed by flow cytometry following remission, plays a substantial role in guiding management plans. Over the past decade, significant advancements in ALL outcomes have been witnessed. Conventional chemotherapy has remarkably reduced mortality rates; however, its intensive nature raises safety concerns and has led to the emergence of treatment-resistant cases with recurrence of relapses. Consequently, The U.S. Food and Drug Administration (FDA) has approved several novel treatments for relapsed/refractory ALL due to their demonstrated efficacy, as indicated by improved complete remission and survival rates. These treatments include tyrosine kinase inhibitors (TKIs), the anti-CD19 monoclonal antibody blinatumomab, anti-CD22 inotuzumab ozogamicin, anti-CD20 rituximab, and chimeric antigen receptor (CAR) T-cell therapy. Identifying the variables that influence treatment decisions is a pressing necessity for tailoring therapy based on heterogeneous patient characteristics. Key predictive factors identified in various observational studies and clinical trials include prelymphodepletion disease burden, complex genetic abnormalities, and MRD. Furthermore, the development of serious adverse events following treatment could be anticipated through predictive models, allowing for appropriate prophylactic measures to be considered. The ultimate aim is to incorporate the concept of precision medicine in the field of ALL through valid prediction platform to facilitate the selection of the most suitable treatment approach.

Clinical features and prognosis of patients with myeloid neoplasms harboring t(7;11)(p15;p15) translocation: a single-center retrospective study

BackgroundFor myeloid neoplasms with t(7;11)(p15;p15) translocation, the prognosis is quite dismal. Because these tumors are rare, most occurrences are reported as single cases. Clinical results and optimal treatment approaches remain elusive. This study endeavors to elucidate the clinical implications and prognosis of this cytogenetic aberration.MethodsThis study retrospectively analyzed 23 cases of myeloid neoplasm with t(7;11)(p15;p15). Clinicopathological characteristics, genetic alterations, and outcomes were evaluated, and the Kaplan-Meier method was employed to construct survival curves.ResultsOf these, nine cases were newly diagnosed acute myeloid leukemia (ND AML), seven presented with relapsed refractory AML (R/R AML), four had myelodysplastic syndrome (MDS), two had secondary AML, and one exhibited a mixed germinoma associated with MDS. Patients with t(7;11)(p15;p15) in AML were primarily younger females who preferred subtype M2. Interestingly, these patients had decreased hemoglobin and red blood cell counts, along with markedly elevated levels of lactic dehydrogenase and interleukin-6, and exhibited the expression of CD117. R/R AML patients exhibited a higher likelihood of additional chromosome abnormalities (ACAs) besides t(7;11). WT1 and FLT3-ITD were the most commonly found mutated genes, and 10 of those instances showed evidence of the NUP98::HOXA9 fusion gene. The composite complete remission rate was 66.7% (12/18), while the cumulative graft survival rate was 100% (4/4). However, the survival outcomes were dismal. Interestingly, the median overall survival for R/R AML patients was 4.0 months (95% CI: 1.7–6.4). Additionally, the type of AML diagnosis or the presence of ACAs or molecular prognostic stratification did not significantly influence clinical outcomes (p = 0.066, p = 0.585, p = 0.570, respectively).ConclusionMyeloid leukemia with t(7;11) exhibits unique clinical features, cytogenetic properties, and molecular genetic characteristics. These survival outcomes were dismal. R/R AML patients have a limited lifespan. For myeloid patients with t(7;11), targeted therapy or transplantation may be an effective course of treatment.

Anti-CD7 allogeneic WU-CART-007 in patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma: a phase 1/2 trial.

Relapsed/refractory T-cell acute lymphoblastic leukemia (ALL)/lymphoma (LBL) represent a significant unmet medical need. WU-CART-007 is a CD7-targeting, allogeneic, fratricide-resistant chimeric antigen receptor T cell product generated from healthy donor T cells. WU-CART-007 was evaluated in a phase 1/2 study with a 3 + 3 dose-escalation design followed by cohort expansion in relapsed/refractory T-ALL/LBL. Patients received one infusion of WU-CART-007 after standard or enhanced lymphodepleting chemotherapy. The primary objectives, to characterize safety and assess the composite complete remission rate, were met. Of 26 patients enrolled, 13 received the recommended phase 2 dose (RP2D) of 900 million cells of WU-CART-007 with enhanced lymphodepletion. The most common treatment-related adverse event was cytokine release syndrome (88.5%; 19.2% grade 3-4). Biochemical abnormalities consistent with grade 2 hemophagocytic lymphohistiocytosis were seen in one patient (3.8%). Grade 1 immune effector cell-associated neurotoxicity syndrome events (7.7%) and one grade 2 acute graft-vs-host disease event occurred. Grade 5 events (11.5%) were due to fungal infection and multi-organ failure. The composite complete remission rate was 81.8% among 11/13 patients evaluable for response at the RP2D. WU-CART-007 at the RP2D demonstrated a high response rate in patients with relapsed/refractory T-ALL/LBL and has the potential to provide a new treatment option. ClinicalTrials.gov registration: NCT04984356.

Impact of twice-daily budesonide foam administration on early clinical response and endoscopic remission in patients with ulcerative colitis: a post hoc analysis.

Early treatment response of ulcerative colitis (UC) symptom resolution is desirable. This post hoc analysis evaluated efficacy outcomes, including endoscopic remission, by responder status and the influence of once-daily (QD) versus twice-daily (BID) budesonide foam dosing in patients with UC. Data were pooled from phase 2 and phase 3 clinical trials of budesonide rectal foam QD or BID or placebo for up to 12weeks. Outcomes were evaluated by treatment and budesonide administration regimen and by responder group: early (rectal bleeding subscore [RBS] 0 from Week 2 through Week 6), delayed (RBS 0 at Week 6), and nonresponder (RBS>0 at Week 6). The main analysis set included 55 (QD) and 120 (BID) budesonide-treated patients and 116 placebo-treated patients. At Week 6, the trend in early response rate was significant among treatment groups (BID, 45.3%; QD, 32.1%; placebo, 12.8%; P<0.0001). Among BID recipients, trends for complete endoscopic remission rate (Mayo endoscopic score [MES]=0) and endoscopic remission rate (MES=0 or 1) were significant among responder status groups (early responder, 67.4% and 95.4%, respectively; delayed responder, 48.1% and 85.2%; nonresponder, 24.0% and 64.0%; P<0.001 for both). Regardless of the administration regimen, most early responders achieved endoscopic remission at Week 6. Among responder status groups, early responders' cumulative non-relapse period was greatest (P=0.07). A BID budesonide administration regimen is preferred to increase the probability of early response and, following endoscopic remission, a better prognosis after stopping treatment.

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

Treatment of Membranous Nephropathy in Chinese Patients: Comparison of Rituximab and Intravenous Cyclophosphamide with Steroids

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on primary membranous nephropathy (PMN). However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥4 g/24 h, serum albumin <30 g/L, and eGFR ≥30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/day and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint (p = 0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, p = 0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, p = 0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, p = 0.03) among patients with massive proteinuria (urine protein ≥8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, p = 0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.

Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study).

For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

Retrospective Evaluation of Survival and Prognostic Factors in Immune Thrombocytopenia: A Single-Center and Cross-Sectional Study.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids (p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia

PurposeT(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML. The aim of this retrospective study was to evaluate the effectiveness of VEN plus AZA (VA) in AE-AML and explore whether adding homoharringtonine (HHT) to VA (VAH) could improve the response.MethodsPatients who received VEN plus AZA and HHT (VAH) or VEN plus AZA (VA) regimens were included in this retrospective study. The endpoints of this study were to evaluate the rate of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups.ResultsA total of 32 AE-AML patients who underwent VA or VAH treatments (newly diagnosed with VA, ND-VA, n = 8; relapsed/refractory with VA, R/R-VA, n = 10; relapsed/refractory with VAH, R/R-VAH, n = 14) were included. The CR (complete remission) /CRi (CR with incomplete count recovery) rate of ND-VA, R/R-VA and R/R-VAH were 25%, 10%, and 64.3%, respectively. Measurable residual disease (MRD) negative was observed in 66.7% of R/R-VAH and none of VA-R/R patients. Co-occurring methylation mutations are associated with poor outcomes with VA but exhibit a more favorable response with VAH treatment. Additionally, patients with c-kit mutation presented inferior outcomes with both VEN-based regimens. All regimens were tolerated well by all patients.ConclusionOur data confirmed the poor response of VA in AE-AML, whether used as frontline or salvage therapy. Adding HHT to VA may improve outcomes and enhance the efficacy of VEN in this population.

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications – a HARMONY study

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.

The efficacy and adverse events of bevacizumab combined with temozolomide in the treatment of glioma: a systemic review and meta-analysis of randomized controlled trials.

To assess the efficacy and adverse events of bevacizumab (BEV) combined with temozolomide (TMZ) in the treatment of glioma. Randomized controlled trials (RCT) involving BEV combined with TMZ in the treatment of glioma were searched using PubMed, Embase and Cochrane library, and a comprehensive meta-analysis was conducted. The primary outcomes were overall survival time (OS) and progression-free survival time (PFS), and the secondary outcome was adverse events. Researchers conducted literature screening, data extraction and quality assessment according to inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis. A total of 8 prospective RCTs of 3,039 cases were included in the meta-analysis. Meta-analysis showed that compared with TMZ alone, BEV combined with TMZ could significantly improve PFS, OS and complete remission rate (CR). A total of 6 studies reported related adverse events, mainly including thrombocytopenia, neutropenia, leukopenia, anemia and fatigue. Combination therapy may have more adverse events but no serious consequences. The combination of BEV and TMZ had a better therapeutic effect on glioblastoma, significantly prolonged the survival time of patients and improved the quality of life. However, some patients are afflicted with the adverse events of combination therapy, and subsequent studies should continue to conduct larger, multi-center RCTs to confirm the findings and explore in depth how to minimize and manage adverse events effectively.

Impact of monocytic differentiation on acute myeloid leukemia patients treated with venetoclax and hypomethylating agents.

Although the combination of venetoclax (VEN) and hypomethylating agents (HMAs) results in impressive efficacy in acute myeloid leukemia (AML), there is still a subset of patients who are refractory. We investigated the outcomes of AML patients with monocytic differentiation who were treated with frontline VEN/HMA. A total of 155 patients with newly diagnosed AML treated with frontline VEN/HMA were enrolled in the study. Monocyte-like AML was identified by flow cytometry with typical expression of monocytic markers, and M5 was identified according to French, American, and British category. We compared the outcomes of patients with different characteristics. The rate of complete remission (CR) and CR with incomplete recovery of blood counts (CRi), progression-free survival (PFS), and overall survival (OS) in monocyte-like AML were inferior to those in nonmonocyte-like AML (CR/CRi rates, 26.7% vs. 80.0%, p < 0.001; median PFS, 2.1 vs. 8.8 months, p < 0.001; median OS, 9.2 vs. 19 months, p = 0.013). CR/CRi rate in M5 was lower than that in non-M5 (60.7% vs. 75.5%, p = 0.049). Multivariate analyses showed that monocyte-like AML was associated with lower odds of CR/CRi and higher risk of progression. Our study suggested that newly diagnosed AML with a monocytic immunophenotype had a poor prognosis with VEN/HMA treatment.