Complete Remission Rate Research Articles

Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients With FLT3-Mutated Acute Myeloid Leukemia (AML): A Multicenter Retrospective Analysis.

Addition of midostaurin to standard "7+3" (cytarabine and anthracycline) significantly prolongs overall and event-free survival. At University of Washington/Fred Hutchinson Cancer Center (UW/FHCC), the standard regimen for newly diagnosed (ND) and relapsed/refractory (R/R) AML is cladribine, high-dose cytarabine, GCSF, and mitoxantrone (CLAG-M); midostaurin is added if FLT3-mutated. There is limited data on the use of FLT3-inhibitors with high-dose cytarabine regimens in AML. This study aimed to evaluate the safety and efficacy of the combination of midostaurin with CLAG-M versus midostaurin plus 7+3 in FLT3-mutated AML patients. This is a retrospective, multicenter review including FLT3-mutated AML patients undergoing (re)induction chemotherapy with either CLAG-M or 7+3 at UW/FHCC, Oregon Health & Science University, and Swedish Cancer Institute. The primary outcome was incidence of adverse events. Secondary outcomes included disease response per ELN2017 criteria and 28-day mortality. Excluded were patients on clinical trials or who started midostaurin 30 days after chemotherapy. Eighty patients treated from September 2016 to December 2023 were included; 36 patients received CLAG-M, and 44 patients 7+3. Baseline characteristics were similar across all institutions. Adverse event rates were similar between the 2 cohorts, except diarrhea and bleeding which were more common in the 7+3 cohort. The rate of complete remission (CR) plus CR with incomplete blood count recovery did not significantly differ between the 2 cohorts: CLAG-M, 86% versus 7+3, 70% (P = 0.11). The toxicity profile of CLAG-M combined with midostaurin is comparable with the combination of 7+3 with midostaurin, and induces high remissions rates in adults with FLT3-mutated AML.

Cyberknife radio-neurosurgery for secreting pituitary adenomas treated with single fraction radio-neurosurgery: A systematic review and meta-analysis.

Stereotactic radiosurgery (SRS) is one of the treatment options for the management of residual or recurrent secreting pituitary adenomas (PA). While the role of radiosurgery (RS) by Gamma Knife (GK) has been clearly established, Cyberknife (CK) RS has been evaluated in fewer series. To perform a systematic review of the literature and meta-analysis, with the aim of focusing on the effect of CK RS on secreting PA. Using PRISMA guidelines, we reviewed articles published between January 1994 and January 2024. The inclusion criteria contained: single fraction RS, biochemical remission, tumor control and complication appearance (hypopituitarism). Were incorporated 8 studies including 152 secreting PA. Vast majority were treated in single fraction 115 (75.6%), with an overall rate of 59.9% (p<0.001). Total remission was encountered in 44/108 patients, for an overall rate of 50.2% (p<0.001). Partial remission was inconsistently reported among studies for 25/55 patients, for an overall rate of 38.8% (p=0.003). Uncontrolled disease was encountered in 36/108 patients, for an overall rate of 32.7% (p<0.001). Tumor control was not separately reported for secreting or non-secreting PA, but attained overall high rates. Single fraction CK radiosurgery is common practice for secreting PA. Our meta-analysis suggests high rates of both total and partial remission (as high as 89% if both taken together), with a complete remission rate of 50.2%. These results encourage the use of single fraction CK RS for secreting PA. To reach high rates of biochemical control, high doses of irradiation should be used.

Effect of Oral Posaconazole on Venetoclax Plasma Concentration and its Efficacy in Patients with Acute Myeloid Leukemia.

BCL-2 was the first gene identified to have antiapoptotic effects, and venetoclax is an oral selective BCL-2 inhibitor, which has great potential in the treatment of patients with acute myeloid leukemia (AML) who are not candidates for intensive therapy. Notably, posaconazole, an oral antifungal drug, is also a strong factor that can affect blood venetoclax concentrations. To the best of our knowledge, the relationship between BCL-2 expression, posaconazole, and venetoclax, as well as their influence on treatment efficacy and the prognosis of patients with AML, has not been reported. In this single-center retrospective study, the relationship between BCL-2 expression and blood venetoclax concentration was analyzed in 35 patients with AML. After that, we explored the differences in curative effect, adverse reactions, and outcomes between patients with different BCL-2 expression levels and patients with different venetoclax concentration levels, respectively. BCL-2 mRNA expression levels were examined by reverse transcription quantitative PCR. Blood venetoclax concentrations were measured using high-performance liquid chromatography- tandem mass spectrometry. The results revealed that among patients with AML, those with lower primary BCL-2 expression had a higher complete remission (CR) rate (p =0.005), overall response (OR) rate (p <0.0001), and progression-free survival time (p =0.04). Posaconazole was revealed to be a strong factor that was able to increase blood venetoclax concentration (p <0.001) and CR rate in the venetoclax plus posaconazole group compared to that in the venetoclax monotherapy group (p =0.002); however, no significant difference was identified in the occurrence of adverse reactions between these groups. Among low and high-blood venetoclax concentration groups, the event-free survival of the former group was significantly higher (p =0.013). Higher levels of BCL-2 expression at initial diagnosis may have adverse effects on the efficacy and prognosis of patients, and higher levels of venetoclax concentration may advance the time of adverse reactions in patients, thus adversely affecting event-free survival (EFS).

Hyper-CVAD and Modified CALGB-10403 Regimens in Adult Patients With Philadelphia-Negative Acute Lymphoblastic Leukemia: A Comparative Study.

Acute lymphoblastic leukemia (ALL) has a higher incidence in Latin America, with adult patients experiencing worse long-term outcomes despite high complete remission (CR) rates. When treated with adult regimens, 3-year overall survival (OS) is approximately 20%. However, adopting pediatric-inspired regimens (PIRs) has shown improved outcomes. We performed a comparative analysis of Hispanic adult patients with newly diagnosed Ph-negative ALL, treated with either a PIR, a modified CALGB 10403 (mCALGB), or the adult regimen Hyper-CVAD between January 2015 and May 2023. The primary endpoint was OS and among secondary endpoints relapse-free survival (RFS). We included 100 patients, 35 were treated with Hyper-CVAD and 65 with mCALGB. Median age was 26 years (range, 20.2-38). The median OS was 54.2 months (95% CI 28.3-80.1), with a non-reached median OS in the mCALGB group (95% CI NR-NR) versus 22.4 months (95% CI 13.7-31) for Hyper-CVAD. The 3-year OS was 64.9% versus 34.9%, p = 0.034. Treatment with mCALGB was independently associated with OS (HR 0.29, 95% CI 0.13-0.66, p = 0.003) and RFS (HR 0.29, 95% CI 0.14-0.59, p < 0.001). Treatment with mCALGB was independently associated with benefits regarding RFS and OS when compared to Hyper-CVAD.

The efficacy and safety of half-dose glucocorticoids combined with rituximab versus high-dose glucocorticoids for initial treatment of minimal change disease: a single-center experience

BackgroundMinimal change disease (MCD) is a podocytopathy more commonly seen in children, but it also accounts for 10%–25% of adult nephrotic syndrome. High-dose oral glucocorticoids were recommended for initial treatment of MCD. However, long-term use of systemic corticosteroids is associated with significant adverse events, such as steroid-induced diabetes and infections. The aim of this study was to investigate the clinical efficacy and safety of half-dose glucocorticoids combined with rituximab (RTX) for the initial treatment of MCD.MethodsWe recruited 74 patients with MCD confirmed by renal biopsy. Twenty patients were treated with RTX alone with 1000 mg at d1 and d15, 28 patients received half-dose prednisolone (0.5 mg/kg) per day combined with RTX with 1000 mg at d1, and 26 patients received high-dose prednisolone (1 mg/kg) per day. Treatment responses, including complete remission (CR) and partial remission (PR), and outcome adverse events such as steroid-induced diabetes and infections were compared among the three groups after 12 months of follow-up.ResultsAt the 12-month follow-up, the CR rates were 50%, 96.4%, and 96.2% for the RTX group, half-dose prednisolone combined with RTX group, and high-dose prednisolone group, respectively. There was no statistical difference between the half-dose prednisolone combined with RTX group and high-dose prednisolone group on CR and PR and kidney function (P &amp;gt; 0.05). Compared with the high-dose prednisolone group, the half-dose prednisolone combined with RTX group had a reduced incidence of adverse events of steroid diabetes (P = 0.041), especially in patients older than 55 years of age.ConclusionThe efficiency of half-dose prednisolone combined with RTX is not inferior to the recommended treatment regimen, and this regimen can effectively reduce the incidence of steroid-induced diabetes in patients with MCD. Moreover, we recommend a half-dose prednisolone combined with RTX treatment for elderly patients with MCD.

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.

Efficacy and safety of rituximab in patients with lupus nephritis: A systematic review and meta-analysis.

Our aim was to systematically evaluate the efficacy and safety of rituximab (RTX) in patients with lupus nephritis (LN). PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, and Wanfang Databases were searched to collect literature on the efficacy and safety of RTX in patients with LN. Odds ratios (ORs), weighted mean differences (WMDs), and standardized mean differences (SMDs) were used to represent treatment efficacy and overall outcome. The outcomes included complete renal remission rate, proteinuria, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine, any adverse events and serious adverse events. We explored the heterogeneity with I2 and assessed publication bias with funnel plot and Egger's test. Nine studies involving 723 patients (254 in the RTX group and 469 in the control group) were included in our systematic review and meta-analysis. RTX resulted in a higher complete renal remission rate (OR: 2.62; 95% CI 1.43 - 4.79, p = 0.024, I2 = 54.7%) than the control group. It significantly decreased SLEDAI scores (WMD = -3.79, 95% CI: -5.78 to -1.8, p < 0.001, I2 = 94.7%) as well as proteinuria (WMD = -0.9, 95% CI: -1.6 to -0.2, p < 0.001, I2 = 97.6%). There were no significant differences in any adverse events and serious adverse events between the RTX group and control group. RTX was an effective therapeutic agent in patients with LN, and it did not increase the risk of adverse events compared to the control group.

Hematopoietic stem cell microtransplantation: current situation and challenges.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as a cornerstone in the treatment of hematological malignancies, recognized for its remarkable efficacy. However, the persistent challenge of graft-versus-host disease (GVHD) continues to represent a significant barrier, often being the leading cause of nonrelapse mortality after allo-HSCT. To address this limitation, hematopoietic stem cell microtransplantation (MST) has emerged as a novel therapeutic strategy that synergistically combines chemotherapy, allo-HSCT, and cellular immunotherapy. This innovative approach is designed to retain the patient's immune function, promote the establishment of microchimerism, and achieve a potent graft-versus-tumor (GVT) response, all while significantly minimizing the risk of GVHD. MST has primarily been applied in the treatment of hematological malignancies, where it has demonstrated promising outcomes, including marked improvements in complete remission rates, overall survival rates, and progression-free survival rates. Moreover, MST facilitates hematopoietic recovery, decreases the likelihood of infections, and reduces the incidence of GVHD, thus contributing to an improved quality of life for patients. A deeper and more comprehensive understanding of MST's mechanisms could enhance its clinical utility and integration into standard treatment protocols. This review aims to explore the underlying mechanisms, current clinical applications, and challenges of MST, shedding light on its potential role in advancing the management of hematological malignancies.

The efficacy and safety of brentuximab vedotin for peripheral T-cell lymphoma: A systemic review and meta-analysis.

Peripheral T-cell lymphoma (PTCL) is an extensive class of heterogeneous diseases with dismal outcomes. Brentuximab vedotin (BV) is an antibody-drug conjugate (ADC) comprising a CD30-directed antibody. This review aimed to evaluate the efficacy and safety of BV for treating PTCL. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies evaluating the efficacy of BV alone or in combination with other drugs for treating PTCL. The primary outcome measures included objective response rate (ORR), complete remission (CR), progression-free survival (PFS), and overall survival (OS). The secondary outcomes included 5-year OS, 5-year PFS, and adverse events. 22 studies involving 1137 patients were included. These studies reported the use patterns of BV, ORR, CR, PFS, OS, and adverse events. The pooled ORR and CR rates were 68% (95% CI: 59%-75%) and 43% (95% CI: 34%-53%). For survival outcomes, the longest median PFS was 8.3 months, and the longest median OS was 26.3 months. The most common adverse event was peripheral neuropathy and neutropenia. The analysis suggested that BV alone or in combination with other drugs improved the response and survival rates in PTCL patients and was associated with tolerable adverse effects.

Single or Double Induction With 7 + 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia.

To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m2 with 90 mg/m2 daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction. Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m2 daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m2, all consecutive patients received 60 mg/m2 daunorubicin once daily. The proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m2 once daily was 54% versus 50% (P = .561), and the 3-year overall survival (OS) was 65% versus 58% (P = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937). The use of 90 mg/m2 daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m2 once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.

Neoadjuvant adebrelimab combined with chemotherapy (cisplatin/carboplatin and etoposide) for limited-stage small-cell lung cancer: a study protocol of phase 2 trial (NIUS)

IntroductionSmall-cell lung cancer (SCLC) is a highly malignant neuroendocrine tumour, and concurrent chemoradiotherapy is the current recommended treatment for limited-stage SCLC. However, the overall survival (OS) of patients with SCLC...

FAP-targeted radioligand therapy with 68Ga/177Lu-DOTA-2P(FAPI)2 enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy

BackgroundFibroblast activation protein (FAP)-targeted radioligand therapy, with immunomodulatory effects, has shown efficacy in both preclinical and clinical studies. We recently reported on a novel dimeric FAP-targeting radiopharmaceutical, 68Ga/177Lu-DOTA-2P(FAPI)2, which demonstrated...

Which Immunosuppressive Therapy should be used in Primary Membranous Glomerulonephritis?

Background: Different results have been reported on immunosuppressive treatments in patients with primary membranous nephropathy. In recent years, it has been determined that antiPLA2R antibodies can be used for the diagnosis of primary membranous glomerulonephritis. The aim of this study was to investigate the treatment responses of patients with primary membranous glomerulonephritis determined by the presence of PLA2-R antibody. Patients and Methods: Sixty patients (M:29, F:31) with membranous glomerulonephritis were retrospectively investigated. The presence of glomerular PLA2R antibodies were investigated by immunohistochemical method from the pathological specimen. Those patients were treated with immunosuppressants (methylprednisolon, cyclophosphamide, cyclosporine, azathioprine), and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB). The treatments were carried out with different combinations. The success of the treatment was defined as complete (&lt;0.3g/day), partial (&lt;3.5g/day or at least 50% reduction) or unresponsive (insufficient reduction) according to the reduction in proteinuria. In the patients, progression risks (low, moderate, high) were divided according to proteinuria and creatinine clearance. The results of immunosuppressive treatments were statistically analyzed, and p&lt;0.05 was accepted significant. Results Glomerular PLA2R antibodies were positive in 50 cases (87.7%), negative in 7 cases (12.2%). The mean duration of treatment of the patients was 23 months (6-58 months). With the treatment of PLA2R antibody-positive patients, 29% developed complete remission, 56% partial remission, and 15% did not respond. Complete remission was achieved only by steroid plus cyclophosphamide or cyclosporine combinations. The overall response (complete plus partial) rates were similar (respectively, 91% and 89%) in cyclophosphamide or cyclosporine treatment with steroids. The reduction rates in proteinuria were 70.6% in patients using cyclophosphamide, steroid, and ARB, and 79.5% in patients using cyclosporine, steroid, and ARB; there was no difference between them (P=0.67). In patients with positive PLA2R antibodies, the risk of progression was low in 25%, moderate in 29%, and high in 46%. When the treatment responses were examined, a lower rate of complete remission and higher partial remission were found in the high-risk group than in the low-risk group. However, overall response rates were not different in risk groups. Conclusion In primary membranous glomerulonephritis, only cyclophosphamide or combinations of cyclosporine and steroids provided complete remission. The complete plus partial response rates were similar in all risk groups.

Microtransplantation improved outcomes in elderly patients with newly diagnosed acute myeloid leukemia: clinical efficacy and mechanisms analysis

ABSTRACT Objective Microtransplantation (MST) has been found to enhance clinical outcomes in elderly patients with newly diagnosed acute myeloid leukemia (AML) compared with chemotherapy alone. It is important to investigate clinical effectiveness and mechanisms. Methods From January 2012 to December 2022, a total of 40 patients over 60 years with newly diagnosed low – and medium-risk AML were analyzed retrospectively, which was divided into two groups: MST group (chemotherapy combined with donor peripheral blood stem cell [PBSC] injection, n = 20) and control group (chemotherapy alone, n = 20). Flow cytometry and commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure changes in the percentage of natural killer (NK) cells and the quantity of interferon IFN-γ. The complete remission (CR), 2-year overall survival (OS) and disease-free survival (DFS) were also calculated following therapy. Results After induction chemotherapy, the 20 MST patients had a CR rate of 60%, a 2-year OS of 61.8%, and a 2-year DFS of 51.6%. Conclusion MST has a faster hematological recovery and a greater CR, both of which can enhance OS and DFS in elderly AML patients. After MST, there is a significant correlation between the percentage of NK cells and the quantity of IFN-γ. This suggests that NK cells and IFN-γ are putative immunologic mechanisms of MST action.

Total neoadjuvant therapy based on short-course radiotherapy versus standard long-course chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis of randomized controlled trials.

We conducted the meta-analysis to compare the therapeutic effects of total neoadjuvant therapy (TNT) based on short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) and long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) according to certain significant randomized controlled trials (RCTs). The researchers retrieved several databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to collect all the relevant literature published since the establishment of the databases until July 30, 2024, and then screened to determine the qualified literature and extracted the relevant information. Finally, RevMan 5.4 software was utilized to conduct the meta-analysis for determining the 95% confidence interval (CI) and pooled risk ratio (RR). There were 9 study indicators, including the pathologic complete remission (pCR) rate, tumor downstaging rate, R0 resection rate, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), acute ≥3 grade toxicity rate, surgery complication rate, and distant recurrence rate. When moderate, even severe, heterogeneity was found, a random-effect model was applied; otherwise, a fixed-effect model was used for the analysis. A total of 6 eligible RCTs and 2259 participants were included in this meta-analysis. Compared with the standard LCCRT, TNT treatment on the basis of SCRT/CCT increased the pCR rate significantly [RR = 1.67, 95% CI (1.36, 2.04), P < 0.00001], especially in ≥ 4 cycles of the CCT arm [RR = 1.77, 95% CI: (1.41-2.23), p < 0.00001], and led to a similar tumor downstaging rate [RR = 0.99, 95% CI (0.85, 1.15), P = 0.92]. Moreover, survival outcomes, distant recurrence rate, and surgical indicators were comparable between the two groups. For LARC patients, the SCRT/CCT regimen not only has a higher pCR rate, equivalent OS, and comparable additional indicators versus standard LCCRT but also shortens the treatment time, costs less, and improves patients' adherence to the innovative anti-tumor therapy; hence, with the concept of acute toxicity control, it could be further widely and safely utilized, especially in resource-limited settings. https://www.crd.york.ac.uk/prospero/, identifier CRD42024600180.

Diabetes Remission After Bariatric Surgery: A 10-Year Follow-Up Study

IntroductionTreatment of type 2 diabetes (T2DM) in patients with obesity can be challenging. Metabolic and bariatric surgery (MBS) has shown promising results in improving glycemic control and even achieving remission in T2DM patients with obesity. However, the durability of glycemic improvements in T2DM patients following MBS remains insufficiently studied.AimDetermine the incidence of durable remission and relapse of T2DM rates 10 years after MBS, characterize the glycemic profile after surgery, and identify factors predicting persistent remission of T2DM.MethodsRetrospective observational study of T2DM patients undergoing MBS between 2010 and 2013. Clinical and analytical assessments were performed preoperatively, at 2- and at 10-years postoperatively. Paired t-tests, Wilcoxon-signed-rank and McNemar tests were used to assess the differences in the metabolic status during the follow-up. Logistic regression models were used to identify predictors of T2DM remission.ResultsNinety-five patients were included (mean age 48.8 ± 9.1 years, mean HbA1c 7.0 ± 1.5%). Ten years after surgery, the rate of complete T2DM remission was 31%, partial remission was 15%, and late recurrence after initial remission was 24%. Patients with lower HbA1c (OR = 0.50; p = 0.05) and taking fewer antidiabetic drugs (OR = 0.31; p = 0.01) preoperatively were more likely to maintain long-term remission. Ten years post-MBS, patients maintained lower fasting plasma glucose (p < 0.001), HbA1c (p < 0.001), number of antidiabetic drugs (p < 0.001), and insulin use (p < 0.001).ConclusionMBS can induce a significant improvement and sustainable remission of T2DM. Early intervention, while patients still have a good glycemic control with a lower number of anti-diabetic drugs, is crucial to achieve long-lasting benefits and a potential "surgical cure" for T2DM.

Optimizing the Treatment of Acute Promyelocytic Leukemia: A Maintenance-Free Strategy for Complete Remission

Background: Acute promyelocytic leukaemia (APL) is a distinct variant of acute myeloid leukaemia (AML), comprising 5-10% of all AML cases. Characterized by the t(15; 17) chromosomal translocation, APL presents a unique challenge due to its associated bleeding manifestations and coagulopathy, emphasizing the need for urgent and specialized management. Methods: This prospective open-label pilot study enrolled ten newly diagnosed APL patients, stratified based on the Sanz risk score. Low and intermediate-risk patients underwent ATRA+ATO induction therapy without chemo, followed by consolidation therapy. High-risk patients received additional single dose chemo Daunorubicin or Mitoxantrone alongside ATRA+ATO induction. The study evaluated patient characteristics, clinical findings, laboratory results, and treatment outcomes, focusing on complete remission (CR) after induction therapy and disease-free survival (DFS) at 3 years. Results: The study observed a 100% CR rate after induction therapy, with favourable 3-year DFS and event-free survival (EFS). No treatment failures, mortality, or relapses were reported. Laboratory findings and clinical outcomes were consistent with the characteristics of APL, including the hematological parameters. The absence of maintenance therapy minimized associated toxicities, supporting the safety and efficacy of the chemotherapy-free ATRA+ATO approach. Conclusion: This pilot study underscores the potential paradigm shift in APL management by demonstrating the safety and efficacy of a chemotherapy-free ATRA+ATO strategy. The results align with the 2023 National Comprehensive Cancer Network (NCCN) update, endorsing the ATRA+ATO regimen for APL. The on-going nature of the research emphasizes its contribution to evolving APL management practices, encouraging further comprehensive evaluations on a broader scale.

Semi-mechanistic population PK/PD model to aid clinical understanding of myelodysplastic syndromes following treatment with Venetoclax and Azacitidine.

Myelodysplastic syndromes (MDS) represent a group of bone marrow disorders involving cytopenias, hypercellular bone marrow, and dysplastic hematopoietic progenitors. MDS remains a challenge to treat due to the complex interplay between disease-induced and treatment-related cytopenias. Venetoclax, a selective BCL-2 inhibitor, in combination with azacitidine, a hypomethylating agent, is currently being investigated in patients with previously untreated higher-risk MDS. We present an integrated semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model developed using preliminary clinical data from an ongoing Phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine in treatment-naïve patients with higher-risk MDS. Longitudinal data from 57 patients were used to develop the model, which accounted for venetoclax PK and azacitidine treatment to describe time dynamics of bone marrow blasts, neutrophils, red blood cells, and platelets. The proliferation and maturation of progenitor cells in the bone marrow to peripheral cells is described via three parallel connected transit models including feedback terms. The model also accounted for bone marrow crowding and its impact on hematopoiesis. Model validation demonstrated adequate goodness-of-fit, visual and numerical predictive checks. Model predicted complete remission (CR) rates and marrow complete remission (mCR) rates closely matched observed rates in the clinical study, and simulated efficacy (recovery of blast count, CR, and mCR rates) and safety (neutropenia and thrombocytopenia) endpoints aligned with expected outcomes from various dosing regimens. Importantly, the semi-mechanistic model may aid understanding and discriminating between disease-driven and drug-induced cytopenias.

Laparoscopic Shull Technique for Uterine Prolapse and Risk of Recurrences: A Retrospective Comparison with Vaginal Hysterectomy.

The objective was to compare the vaginal and laparoscopic approaches with natural tissue vaginal repair of pelvic organ prolapse (POP) in terms of recurrence rate and complete remission rate (CRR) of symptoms. This retrospective cohort study analyzed women who underwent hysterectomy for uterine prolapse at two Italian hospitals between October 2021 and March 2023. Group A included 89 patients who received vaginal hysterectomy and colposuspension (VCH), whereas group B included 58 patients who underwent laparoscopic hysterectomy followed by laparoscopic colposuspension sec Shull (LPSS). The study included 147 patients with comparable baseline characteristics regarding menopausal age and body mass index. Concerning preoperative data, it is worth mentioning that group A had a higher proportion of patients with more than two previous deliveries and, overall, more severe prolapse stages. Concerning postoperative results, the patients undergoing laparoscopic surgery had longer operation times than group A. Moreover, group B had a higher recurrence rate after surgery (5.6% vs 13%, p = 0.057). Kaplan-Meier analysis indicated a lower rate of prolapse-free patients over time in group B. Cox regression showed a higher hazard ratio for recurrence in the LCSS group than in the VCH group.Complete remission rates for urinary symptoms varied, with group B showing higher CRR for stress incontinence (33% vs 71%, p < 0.001). Both VCH and LCSS are effective for POP treatment, with VCH showing better outcomes in terms of symptom remission and shorter operation times. At the same time, LCSS had better CRR for stress incontinence but a higher recurrence rate. Further high-quality prospective studies are needed to confirm these findings and determine the best surgical approach for POP.

Efficacy and Safety of Venetoclax Plus Azacitidine for Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes.

Patients with higher-risk myelodysplastic syndromes (HR MDS) have a median survival of ~1.5 years with azacitidine, and hematopoietic stem cell transplantation is their only curative option. Therefore, improved therapies are needed. This phase 1b study investigated safety and efficacy of venetoclax, a selective BCL-2 inhibitor, at the recommended phase 2 dose (RP2D: 400 mg for 14 days/28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days/28-day cycle) for treatment-naive HR MDS (NCT02942290). Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). As of May 2023, 107 patients received venetoclax and azacitidine combination at the RP2D. Best response of CR or marrow CR was observed in 29.9% and 50.5% of patients (mOR, 80.4%). Median OS was 26.0 months, with 1-year and 2-year survival estimates of 71.2% and 51.3%, respectively. Of 59 patients who were red blood cell and/or platelet transfusion-dependent at baseline, 24 (40.7%) became transfusion-independent on study, including 11 (18.6%) who also achieved CR. Fifty-one (49.0%) of 104 evaluable patients achieved HI. Median TTNT excluding transplantation was 13.4 months. Adverse events reflected known safety profiles for venetoclax and azacitidine, including constipation (53.3%), nausea (49.5%), neutropenia (48.6%), thrombocytopenia (44.9%), febrile neutropenia (42.1%), and diarrhea (41.1%). Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes. A phase 3 study (NCT04401748) is ongoing to confirm survival benefit of this combination.