Difference In 5-year Overall Survival Research Articles

Allogeneic blood or marrow transplantation using haploidentical grandchildren donors and post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis.

High-dose post-transplant cyclophosphamide allows safe and effective use of allografts from haploidentical relatives (siblings, parents and children) in patients undergoing allogeneic blood or marrow transplant (alloBMT). More recently, second- and third-degree relatives have also been shown to be safe allograft donors. An increasing number of older patients undergoing alloBMT have been receiving allografts from haploidentical donors. However, older patients are more likely to have older siblings and children, and older donor age is associated with worse outcomes. In the current study, we report the safety and utility of grandchildren as haploidentical donors and compared with children as donors in patients undergoing alloBMT. We compared characteristics and outcomes of alloBMT patients aged 55 years and older with children older than 30 years as donors (C group; n = 276) and those with grandchildren as donors (GC group; n = 40). Because many important baseline characteristics predict outcomes after alloBMT, we performed propensity score matched analysis based on recipient age, alloBMT year, disease, graft source and haematopoietic cell transplantation comorbidity index (HCT-CI). The median age of recipients was 67 years (range 55-79) in the C group and 73 years (range 57-78) in the GC group. More than 70% of recipients in the GC group were older than 70 years, compared with 27% in the C group. The median donor age was 37 years (range 31-52) in the C group and 20 years (range 14-34) in the GC group. More patients in the GC group had HCT-CI scores ≥3 than in the C group (32.5% vs. 23%, p = 0.27). Two-year overall survival did not differ between the two groups (GC 62% vs. C 60%, hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.53-1.75, p = 0.90) despite recipients of allografts from grandchildren being older. The 2-year RFS was 55% in the C group compared with 50% in the GC group (HR 1.05, 95% CI 0.62-1.77, p = 0.85). Non-relapse mortality subdistribution [SD] (SDHR 1.36, 95% 0.70-2.63, p = 0.36), relapse (SDHR 0.72, 95% CI 0.33-1.58, p = 0.42) or relapse-free survival (HR 1.05, 95% CI 0.62-1.77, p = 0.85). Propensity score matching analysis showed no significant differences in 2-year overall survival (GC 64% vs. C 53%; HR 0.77, 95% CI 0.42-1.42, p = 0.40), non-relapse mortality (SDHR 1.26, 95% 0.66-2.41, p = 0.48), relapse (SDHR 0.57, 95% CI 0.21-1.52, p = 0.26) or relapse-free survival (HR 0.94, 95% CI 0.57-1.54, p = 0.81). Our results indicate that outcomes of alloBMT patients with grandchild donors are similar to those with child donors, despite recipients' older age and higher comorbidities in the GC group. Grandchildren should be considered when selecting a donor for older alloBMT recipients.

First-line treatment of severe aplastic anemia: immunosuppressive therapy plus eltrombopag versus haploidentical hematopoietic stem cell transplantation, a multicenter prospective study.

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 109/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.

Chidamide combined with a modified Bu-Cy conditioning regimen improves survival in patients with T-cell acute lymphoblastic leukemia/lymphoma undergoing allogeneic hematopoietic stem cell transplantation

This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period. The leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse-related mortality (NRM) were evaluated. Patients in the Chi group were associated with lower 2-year CIR (19.0 vs. 41.4%, P = 0.030), better 2-year LFS (76.1 vs. 48.1%, P = 0.014), and had no significant difference in 2-year OS (80.5 vs. 66.4%, P = 0.088). Patients with minimal residual disease (MRD) positive before HSCT in the Chi group exhibited an advantage in 2-year LFS and a trend towards better 2-year OS (75.0 vs. 10.2%, P = 0.048; 75.0 vs. 11.4%, P = 0.060, respectively). Multivariable analysis showed that the chidamide intensified regimen was independently associated with better LFS (HR 0.23; 95%CI, 0.08–0.63; P = 0.004), and showed no significant impact with OS for all patients (HR 0.34, 95%CI, 0.11–1.07; P = 0.064). The cumulative incidence rates of grade II-IV aGVHD were similar (36.4 vs. 38.6%, P = 0.858). 20 patients in Chi group evinced an elevation in γ-glutamyltransferase, as compared to the mBuCy group (90.9 vs. 65.9%, P = 0.029). No transplantation-related mortality was documented within the first 100 days after transplantation. The results demonstrate that the chidamide intensified regimen may be an effective and acceptable safety option for T-ALL/LBL undergoing allo-HSCT, and further validation is needed.

Neoadjuvant chemotherapy versus surgery plus adjuvant chemotherapy for locally advanced colon cancer: A meta-analysis of randomized controlled trials.

e15631 Background: The primary treatment for colon tumors is surgical resection, but the use of neoadjuvant chemotherapy (NAC) in managing locally advanced cases remains a subject of ongoing debate. We conducted a thorough meta-analysis, including randomized clinical trials (RCTs), to assess the oncological safety of neoadjuvant chemotherapy (NAC) in colorectal tumor patients. Methods: We systematically searched in PubMed, Scopus, Google Academic and Cochrane Library in January 2024 for studies that directly compared NAC versus surgery in patients with T3-4, N0-2, M0 colorectal cancer. We assessed overall survival (OS) and disease-free survival (DFS). We calculated odds ratios (ORs) and hazard ratios (HRs) using generic inverse variance in Review Manger 5.4. Heterogeneity was assessed using I² statistics. Results: We included seven RCTs, involving 4,391 patients. Among them, 53.5% underwent NAC, with a median age of 61.41 years and an average follow-up of 62.35 months. The comprehensive analysis revealed no statistically significant differences in 3-year OS (OR: 1.20, 95% CI: 0.91 to 1.59, p = 0.20), more than 2 years DFS (OR: 0.88, 95% CI: 0.37 to 2.13, p = 0.78) and five-year DFS (OR: 1.09, 95% CI: 0.83 to 1.43, p = 0.55). Employing a time-to-effect modeling approach, there was no significant difference in OS (HR: 1.04, 95% CI: 0.63 to 1.70, p = 0.88) or DFS (HR: 0.86, 95% CI: 0.7 to 1.06, p = 0.16); (Table 1). Conclusions: Our systematic review and meta-analysis of seven RCTs showed that neoadjuvant chemotherapy compared with surgery followed by adjuvant chemotherapy had similar overall survival and disease-free-survival in patients with locally advanced colon cancer. [Table: see text]

A comparison of frailty measures in population-based data for patients with colorectal cancer.

Numerous studies have revealed age-related inequalities in colorectal cancer care. Increasing levels of frailty in an ageing population may be contributing to this, but quantifying frailty in population-based studies is challenging. To assess the feasibility, validity and reliability of the Hospital Frailty Risk Score (HFRS), the Secondary Care Administrative Records Frailty (SCARF) index and the frailty syndromes (FS) measures in a national colorectal cancer cohort. Retrospective population-based study using 136,008 patients with colorectal cancer treated within the English National Health Service. Each measure was generated in the dataset to assess their feasibility. The diagnostic codes used in each measure were compared with those in the Charlson Comorbidity Index (CCI). Validity was assessed using the prevalence of frailty and relationship with 1-year survival. The Brier score and the c-statistic were used to assess performance and discriminative ability of models with included each measure. All measures demonstrated feasibility, validity and reliability. Diagnostic codes used in SCARF and CCI have considerable overlap. Prevalence of frailty determined by each differed; SCARF allocating 55.4% of the population to the lowest risk group compared with 85.1% (HFRS) and 81.2% (FS). HFRS and FS demonstrated the greatest difference in 1-year overall survival between those with the lowest and highest measured levels of frailty. Differences in model performance were marginal. HFRS, SCARF and FS all have value in quantifying frailty in routine administrative health care datasets. The most suitable measure will depend on the context and requirements of each individual epidemiological study.

Obesity paradox: is a high body mass index positively influencing survival outcomes in gynecological cancers? A systematic review and meta-analysis.

Obesity represents an exponentially growing preventable disease leading to different health complications, particularly when associated with cancer. In recent years, however, an 'obesity paradox' has been hypothesized where obese individuals affected by cancer counterintuitively show better survival rates. The aim of this systematic review and meta-analysis is to assess whether the prognosis in gynecological malignancies is positively influenced by obesity. This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting the impact of a body mass index (BMI) of >30 kg/m2 compared with <30 kg/m2 in patients with gynecological cancers listed in PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for quality assessment of the selected articles. Twenty-one studies were identified for the meta-analysis, including 14 108 patients with cervical, ovarian, or endometrial cancer. There was no benefit in 5-year overall survival for obese patients compared with non-obese patients (OR 1.2, 95% CI 1.00 to 1.44, p=0.05; I2=71%). When pooling for cancer sub-groups, there were no statistically significant differences in 5-year overall survival in patients with cervical cancer and 5-year overall survival and progression-free survival in patients with ovarian cancer. For obese women diagnosed with endometrial cancer, a significant decrease of 44% in 5-year overall survival (p=0.01) was found, with no significant difference in 5-year disease-free survival (p=0.78). According to the results of the present meta-analysis, a BMI of ≥30 kg/m2 does not have a positive prognostic effect on survival compared with a BMI of <30 kg/m2 in women diagnosed with gynecological cancers. The existence of the 'obesity paradox' in other fields, however, suggests the importance of further investigations with prospective studies.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78years). This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with GATA2 Gene Mutation

To investigate the clinical characteristics, coexisting gene mutations and prognosis of acute myeloid leukemia (AML) patients with GATA2 gene mutation. The clinical data of 370 newly diagnosed AML patients treated in our hospital from January 2008 to January 2021 was analyzed retrospectively, the next-generation sequencing technology was used to detect the mutated genes in those patients. The clinical characteristics of AML patients with GATA2 mutations, the co-mutated genes of GATA2 mutations, and the effect of GATA2 mutation on prognosis were analyzed. A total of 23 patients (6.2%) with GATA2 mutation was detected in 370 AML patients. Compared with GATA2 non-mutation group, patients in GATA2 mutation group were mostly normal karyotypes (P =0.037) and in low-risk cytogenetic stratification (P =0.028). The incidence of CEBPAdm and NRAS in GATA2 mutation group was significantly higher than that in GATA2 non-mutation group (P =0.010, P =0.009). There were no statistically significant differences between the two groups in terms of sex, age, white blood cell count (WBC), platelet count, hemoglobin, bone marrow (BM) blast, induction chemotherapy regimen and CR rate (P >0.05). Among the 23 patients with GATA2 mutation, the most common co-mutated genes were CEBPAdm, NRAS (both 39.1%), NPM1, FLT3, TET2, WT1 (all 17.4%), ASXL1 and IDH1 (both 13.0%). Survival analysis showed that there was no statistical difference in 5-year overall survival (OS) and leukemia-free survival (LFS) rates between patients with and without GATA2 mutations in whole cohort (n=370) (P =0.306, P =0.308). Among 306 patients without CEBPAdm, the 5-year OS and LFS rates in GATA2 mutation group showed an increasing trend compared with GATA2 non-mutation group, but the difference was not statistically significant (P =0.092, P =0.056). Among 64 patients with CEBPAdm, there was no statistically significant difference in 5-year OS rate between the GATA2 mutation group and the GATA2 non-mutation group (P =0.104), but the 5-year LFS rate of the GATA2 mutation group was significantly decreased (P =0.047). Among the 23 patients with GATA2 mutation, 16 cases received the "3+7" induction regimen, of which 12 cases received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7 cases received the "DCAG" induction regimen, of which 3 cases received allo-HSCT. The CR rate was not statistically different between the "3+7" regimen group and the "DCAG" regimen group (P =1.000). The 5-year OS rate and LFS rate in the transplantation group were significantly higher than the chemotherapy group (P =0.021, P =0.020). GATA2 mutation is more common in AML patients with normal karyotype and low-risk cytogenetic stratification, and it is significantly associated with CEBPAdm and NRAS co-mutations. The prognostic significance of GATA2 is influenced by CEBPAdm. The choice of "3+7" or "DCAG" induction regimen in patients with GATA2 mutation does not affect their CR rate, while the choice of allo-HSCT can significantly improved the prognosis compared with chemotherapy only.

Contemporary outcomes for resected type 1-3 gastroesophageal junction adenocarcinoma: a single-center experience

BackgroundSurgical resection remains the mainstay of treatment for tumors of the gastroesophageal junction (GEJ). However, contemporary analyses of the Western experience for GEJ adenocarcinoma are sparsely reported. MethodsPatients with GEJ adenocarcinoma undergoing resection between 2012 and 2022 at a single institution were grouped based on Siewert subtype and analyzed. Pathologic and treatment related variables were assessed with relation to outcomes. ResultsA total of 302 patients underwent resection: 161 (53.3%) with type I, 116 (38.4%) with type II, and 25 (8.3%) with type III tumors. Most patients received neoadjuvant therapy (86.4%); 86% of cases were performed in a minimally invasive fashion. Anastomotic leak occurred in 6.0% and 30-day mortality in only 0.7%. The rate of grade 3+ morbidity was lower for the last 5 years of the study than for the first 5 years (27.5% vs 49.3%, P < .001), as was median length of stay (7 vs 8 days, P < .001). There was a significantly greater number of signet ring type tumors among type III tumors (44.0%) than type I/II tumors (11.2/12.9%, P < .001). Otherwise, there was no difference in the distribution of pathologic features among Siewert subtypes. Notably, there was a significant difference in 3-year overall survival based on Siewert classification: type I 60.0%, type II 77.2%, and type III 86.3% (P = .011). Siewert type I remained independently associated with worse survival on multivariable analysis (hazard ratio, 4.5; P = .023). ConclusionsIn this large, single-institutional series, operative outcomes for patients with resected GEJ adenocarcinoma improved over time. On multivariable analysis, type I tumors were an independent predictor of poor survival.

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Impact of CD34 positive cell dose in donor graft on the outcomes after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide – A retrospective single-center study with a Japanese cohort

BackgroundHaploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34+ cell dose in grafts has not been fully elucidated. ObjectiveWe aimed to explore the impact of CD34+ cell dose on outcomes after haplo-PBSCT with PTCy. Study DesignWe retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors. ResultsThere were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34+ cells was 4.9 × 106 /kg in 57 haplo-PBSCT and 4.5 × 106 /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34+ cell at a dose of ≥4.0 × 106 /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD. ConclusionOur data suggest that a higher dose of CD34+ cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.

Molecular markers as possible efficacy predictors of targeted therapy for myelofibrosis: single-center study

Background. Targeted therapy is the most promising in the treatment of myelofibrosis, but it is necessary to search for the reasons limiting its effectiveness. There are known factors negatively affecting the development of myelofibrosis, but data on their negative impact in the context of targeted therapy are scarce.Aim. Assessing the impact of cytogenetic and genetic abnormalities on the course and therapy results for primary and secondary myelofibrosis during ruxolitinib therapy.Materials and methods. The prospective study included 106 patients with myelofibrosis in the chronic phase (53 (50 %) men and 53 (50 %) women) who received ruxolitinib at the Moscow City Hematology Center, S.P. Botkin City Clinical Hospital. The median age of patients was 62 (18–84) years. The median disease duration before initiation of ruxolitinib therapy was 79 (1–432) months. Before therapy, genetic studies were performed, including next-generation sequencing. The median duration of ruxolitinib therapy was 33 (1–111) months. The influence of the cytogenetic landscape, driver mutations, allele burden of JAK2 (over time) and CALR, additional mutations on the dynamics of symptoms, spleen size, achievement of hematological response, overall survival, progression-free survival, survival without blast crisis and without progression of myelofibrosis with targeted therapy was assessed.Results. The studied genetic factors did not have a significant correlation with hemogram parameters. The hematological response in patients with JAK2 and CALR mutations compared favorably with the response in the groups with the MPL mutation and triple negative status (TNS). Higher hematological response rate was obtained in the group with initially low allele burden &lt;50 % of JAK2 or CALR. Significant differences in 5-year overall survival were found between groups of patients with TNS and JAK2 and CALR mutations (p &lt;0.05); with CALR allele burden &lt;50 % and ³50 % before initiation of ruxolitinib therapy (p = 0.01); the presence or absence of positive dynamics of the JAK2 allele burden during treatment (p &lt;0.05); additional mutations assigned to different pathogenicity groups (p &lt;0.05); with different number of pathogenic mutations (1 or ³2), the presence or absence of pathogenic mutations in the ASXL1 (p = 0.002) and SETBP1 (p = 0.00001) genes. The 5-year progression-free survival was significantly different in cohorts of patients with or without positive dynamics of the JAK2 allelic load during treatment (p &lt;0.05); additional mutations assigned to different pathogenicity groups (p &lt;0.05); with a different number of pathogenic mutations (1 or ³2), the presence or absence of a pathogenic mutation of the SETBP1 gene (p = 0.003). Progression-free survival did not correlate with the type of driver mutation or its absence; however, all patients with TNS died from myelofibrosis progression. Significant differences in 5-year blast crisis-free survival were observed between groups with JAK2 and MPL mutations (p = 0.001), JAK2 and TNS (p = 0.002); difference in 5-year survival without progression of fibrosis – between groups with pathogenic and benign (p = 0.031); uncertain and benign (p = 0.001) mutations.Conclusion. The study identified genetic markers associated with decreased efficacy of ruxolitinib therapy.

Survival Outcome of Autologous or Allogeneic Stem Cell Transplantation in 49 Patients with Extranodal NK/T-Cell Lymphoma

Objective:Extranodal NK/T-cell lymphoma (ENKTL) is an uncommon tumor featured by high invasiveness, the ease of developing drug resistance, low curative rate, and short survival time. Hematopoietic stem cell transplantation (HSCT) is now recommended for patients with advanced or relapsed/refractory (r/r) ENKTL, but which HSCT is the most suitable remains to be conclusively determined. Here, we performed a retrospective single-center study to compare the prognostic role of autologous and allogeneic HSCT after induction chemotherapy in ENKTL patients. Methods: Clinical data on 49 ENKTL patients who underwent HSCT in the First Affiliated Hospital of Soochow University from 8/2007 to 9/2022 was reviewed. We divided all patients into two subgroups: cohort A) auto-HSCT and cohort B) allo-HSCT. Observation period started from the day of stem cell infusion in both cohorts. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and non-relapse mortality (NRM). NRM was defined as death from any cause related to transplantation without evidence of lymphoma progression. Results: Of 49 patients included, 28 (57%) patients received auto-HSCT (cohort A), while 21 (43%) patients received allo-HSCT (cohort B). The two cohorts of patients were different in some terms of baseline characteristics (Figure A). A total of 8 patients with stageⅡdisease received transplantation due to r/r status or primary lesions beyond the nasal area. The patients in cohort B were younger at the time of transplant (median age: 33 years vs. 37 years, p=0.0031) and had a higher proportion of bone marrow involvement (7% vs. 43%, p=0.005). After a median follow-up of 35 months, patients who received allo-HSCT had a worse prognosis compared to patients who underwent auto-HSCT (2-year OS:61% vs 96%, p=0.0015). There was no transplantation-related mortality in the auto-HSCT group, while the NRM was 33.3% in the allo-HSCT group. Limiting the analysis to only patients with complete remission (CR) (allo-HSCT=13, auto-HSCT=25) before HSCT, no differences in 2-year OS and PFS were reported despite 61% vs 4% bone marrow involvement, respectively (76% vs 96% OS and 76.9% vs 84.1% PFS at +24 months, p&amp;gt;0.05). In the allo-HSCT group, patients who achieved first CR(CR1) before HSCT showed higher OS and lower NRM rates compared to those without CR1, with 2-year OS of 88.9% and NRM of 11.1% (p=0.028, p=0.06, respectively). In terms of donor sources, no significant difference in PFS and OS was observed in patients who received haploid conjugate (n = 14) vs. HLA-matched related and unrelated donors(p&amp;gt;0.05). Conclusions: Overall, consolidation therapy with HSCT improved OS in patients with advanced or relapsed/refractory ENKTL who achieved CR after induction therapy. Given the high NRM in the allo-HSCT, auto-HSCT is probably the preferred clinical option in most patients and allo-HSCT may be more appropriate for younger patients with bone marrow involvement and CR1 acquired before transplantation. Larger studies are needed to validate our results.

Early Elevation of Absolute Eosinophil Count after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Chronic Graft-Versus-Host Disease in Children

BACKGROUND Chronic graft-versus-host disease (cGVHD) is the most frequent late complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with non-relapse mortality. If recipients with cGVHD are not properly treated at the appropriate time, cGVHD can lead to severe complications. Therefore, early prediction of cGVHD is required to improve quality of life among the pediatric survivors who undergo allo-HSCT. The significance of eosinophilia in peripheral blood after allo-HSCT remains to be elucidated. Previous studies found that eosinophilia after allo-HSCT reduced the risk of relapse of malignancies or non-relapse mortality and was also associated with cGVHD. However, the subjects of these reports were mainly adults and there were limited data focused on eosinophilia after allo-HSCT in children. The aim of this study was to evaluate whether an early elevation of absolute eosinophil count after allo-HSCT was associated with the development of cGVHD in children. METHODS A total of 165 consecutive patients who received allo-HSCT in our institute were included. Patients who had previously received allo-HSCT, relapsed or died before day 100, and did not achieve engraftment, were excluded. Eosinophilia was defined as an eosinophil count of more than 500 /µL in peripheral blood within 60 days of stem cell infusion. The primary outcome of the present study was the development of cGVHD. RESULTS In our cohort, eosinophilia was detected in 67 patients (40.6%), with a median maximum eosinophil count of 1,050 /µL (range, 504 - 7,812 /µL) at a median of 40 days (range, 24 - 59 days), while median maximum eosinophil count in those without eosinophilia was 189 /µL (range, 0 - 495 /µL). There were no significant differences between the patients with or without eosinophilia in disease type, graft source, donor type, conditioning regimen, and GVHD prophylaxis and treatment. The median time from day 0 to the date of diagnosis of cGVHD was 120 days (range, 100 - 1,302 days). The cumulative incidence rate of cGVHD at 3 years in the entire cohort was 39.3% (95% confidence interval: 32.2 - 47.4). Patients with eosinophilia had a higher 3-year cumulative incidence rate of cGVHD, compared with those without eosinophilia (49.1% vs. 32.7%, P = 0.007). Cox proportional hazards model analysis with adjustments for the potential confounding factors of HLA mismatched donor, unrelated donor, aGVHD, use of ATG as conditioning regimen revealed that eosinophilia was associated with an increased risk of cGVHD (adjusted hazard ratio: 2.12; 95% confidence interval: 1.16-3.85, P = 0.014). In the 165 patients who underwent allo-HSCT, there was no significant difference in 5-year overall survival (OS) between the eosinophilia and the non-eosinophilia groups (80.1% vs. 80.5%, P=0.76). In the 121 patients with malignant diseases, there was no significant difference in 5-year OS between the eosinophilia and the non-eosinophilia groups (75.5% vs. 76.3%, P = 0.70). There was also no significant difference in 5-year disease-free survival between the eosinophilia and the non-eosinophilia groups (69.1% vs. 77.1%, P = 0.34). On the other hand, there was a significant difference in 5-year GVHD-free relapse-free survival between the eosinophilia and the non-eosinophilia groups (41.1% vs. 62.4%, P = 0.04). DISCUSSION &amp; CONCLUSION In the present study, we revealed that an early elevation of absolute eosinophil count after allo-HSCT was associated with cGVHD in children. Because eosinophilia after allo-HSCT occurs before the development of cGVHD, early eosinophilia after allo-HSCT may predict the development of cGVHD in children.

Safety and Efficacy of Outpatient Myeloablative Busulfan Conditioning in Allogeneic Stem Cell Transplantation

INTRODUCTION: Busulfan-based regimens are the backbone of myeloablative conditioning (MAC) in allogeneic hematopoietic stem cell transplant (allo-HSCT), particularly for patients (pts) with Acute Myelogenous Leukemia (AML). However, literature on busulfan conditioning administered in the outpatient (OP) setting is limited. Here, we investigate the safety and efficacy of OP busulfan as compared to standard inpatient (IP) administration. METHODS: Pts &amp;gt; 18 years of age who received pharmacokinetically dose adjusted IV busulfan (130 mg/m2 x 4 days) conditioning prior to HSCT between January 2019 and April 2023 at our institution were included in this retrospective analysis. Pts who received non-myeloablative conditioning or who underwent a haploidentical HSCT were excluded. All pts undergoing HSCT were classified as having low-, intermediate-, or high-risk disease by the Disease Risk Index. Pts with AML were classified as having favorable, intermediate, or adverse disease by 2022 ELN classification. CIBMTR guidelines were used to determine neutrophil and platelet engraftment. Oral mucositis was graded per the World Health Organization scale. Clinical grading of acute graft-vs-host disease (AGVHD) was assigned per standard criteria. Adverse events (AEs) were reported in accordance with the CTCAE, v.5. Categorical variables were compared using the Fisher's Exact test. Continuous variables were compared using the Wilcoxon Rank-Sum test. Overall survival (OS) was defined as time from HSCT to time of death from all-cause mortality. Relapse-free survival (RFS) was defined as time from HSCT to time of relapse or non-relapse mortality. The Kaplan-Meier method was used to estimate OS and RFS. Survival differences between cohorts were compared using the Log-rank test. All hypothesis testing was two-sided and conducted at a significance level of 0.05. RESULTS: In total, 54 pts met eligibility criteria; 43 IP and 11 OP. The OP cohort was younger than the IP cohort (35 years vs 47 years median age; p=0.0284). All other patient, disease, and transplant characteristics were similar between cohorts. The majority of pts were male (IP: 56%, OP: 55%) and White/Caucasian (IP: 100%, OP: 91%). AML (IP: 88%, OP: 82%) was the most common indication for HSCT. Most pts were in CR1 (IP: 74%, OP: 89%) and had intermediate risk disease by both DRI (IP: 84%, OP: 64%) and 2022 ELN classification (IP: 62%, OP: 67%). PBSCT (IP: 88%, OP: 91%) and 10/10 MUD (IP: 67%, OP: 45%) were the most common types of HSCT. The majority of pts received a conditioning regimen of Flu/Bu4 (IP: 58%, OP: 55%). The use of PTCy was comparable between groups (p=0.6593). Of the 11 pts who received OP busulfan, 1 had to complete their conditioning IP after experiencing a seizure in the setting of prior meningitis. Between the 2 cohorts, there was no significant difference in the incidence of AEs &amp;gt; grade 2 (p=1), grade 2 AEs (p=0.8695), grade 3 AEs (p=0.7592), grade 4 AEs (p=0.2487), and grade 5 AEs (p=0.6457) within 30 days of conditioning. Incidences of transplant-related GI toxicities, including nausea (p=1), vomiting (p=0.4979), diarrhea/enteritis (p=1), and mucositis (oral: p=0.6102, GI: p=0.2821) were similar. There was no difference in time to neutrophil (p=0.1606) or platelet engraftment (p=0.9742). Length of hospitalization was shorter in the OP vs IP cohort (18 vs 24 days; p&amp;lt;0.0001). During hospitalization, there was no difference in the incidences of neutropenic fever (p=1), infection (p=0.5104), ICU transfer (p=1), or engraftment syndrome (p=0.7076). Number of infections per patient during hospitalization were comparable (p=0.3764). D30 chimerism was similar IP vs OP. Within 180 days of HSCT, there was no difference in the incidence of AGVHD (p=0.5152) or Grade II-IV AGVHD (p=1). Differences in 2-year OS (LR=0.2200) and 4-year RFS (LR=0.3144) were not significant. CONCLUSION: In pts undergoing MAC allo-HSCT with IV busulfan,OP administration shortens the length of hospitalization without delaying engraftment or increasing the risk of toxicity, neutropenic fever, infection, or ICU admission. Additionally, D30 chimerism, rates of engraftment syndrome and AGVHD, and survival were not affected. This makes OP busulfan an attractive option for transplant centers and their pts.

Autologous Transplant (auto-HCT) Is Associated with Improved Clinical Outcomes Compared to CAR-T Therapy in Patients (pts) with Large B-Cell Lymphoma (LBCL) Achieving a Complete Remission

Introduction: CAR-T therapy is the standard of care for pts with relapsed LBCL as early as in the second line in those with early relapse or with primary refractory disease. In practice, pts who are intended to receive CAR-T, commonly require interim therapy before leukapheresis, wherein a small fraction may achieve a complete remission (CR). Having chemosensitive disease, these pts can be considered for auto-HCT. Also, there are reports indicating the efficacy of CAR-T therapy in CR pts (Strati et al., Haematologica, 2023; Wudhikarn et al., Blood Adv, 2022). We compared the outcome of pts with LBCL who received CAR-T vs. auto-HCT while in a CR. Methods: Pts aged 18-75 years with DLBCL or primary mediastinal lymphoma who received CAR-T (between 2018-2021) or auto-HCT (between 2015-2021) while in a CR by PET or CT were included in this analysis using the data from the Center for International Blood &amp; Marrow Transplant Research (CIBMTR) registry. Primary endpoints included progression-free survival (PFS) and overall survival (OS). Treatment-related mortality (TRM) and relapse rate were among the secondary endpoints. Results: We identified 360 pts with LBCL who were in a CR before receiving CAR-T (n=79, tisa-cel 53%, axi-cel 46%, and liso-cel 1%) or auto-HCT (n=281). Median follow-up was 24.7 months (range 3.3-49.4) for the CAR-T cohort and 49.7 months (range 3.0-95.4) for the auto-HCT cohort. Selected baseline characteristics are shown in Table 1. CRs were confirmed by PET scan in 90% of CAR-T pts and 99.6% of auto-CAR-T pts (p &amp;lt; 0.01). The most common lymphodepletion regimen for CAR-T was Cy/Flu (82.3%) and the most common conditioning regimen for auto-HCT was BEAM (77.6%). Thirty-seven (13.2%) of auto-HCT pts had a later CAR-T but no pts from the CAR-T cohort had subsequent auto-HCT. In univariate analysis, treatment with CAR-T was associated with a higher rate of relapse at 2 years (48% vs. 27.8%; p &amp;lt; 0.001), a lower rate of 2-year PFS (47.8% vs. 66.2%; p &amp;lt; 0.001) and lower 2-year OS (65.6% vs. 78.9%; p=0.037). There was no difference in rates of 2-year TRM (4.1% vs. 5.9%; p=0.673). Similarly, focusing on patients with early (12 months) treatment failure (CAR-T =57 and auto-HCT=163), treatment with CAR-T was associated with a higher 2-year relapse rate (45.9% vs. 22.8%; p &amp;lt;0.001) and an inferior 2-year PFS (48.3% vs.70.9%.; p &amp;lt;0.001) compared to auto-HCT (figure-2) while there was no difference in 2-year OS or TRM. In the multivariable analysis of outcomes, treatment with CAR-T was associated with higher risk of relapse (HR 2.18; p &amp;lt; 0.0001) and an inferior PFS (HR 1.83; p=0.0011) compared to auto-HCT. There was no difference in the risk of TRM (HR 0.59; p=0.36) or OS (HR 1.44; p=0.12). Conclusions: In pts with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with a lower relapse rate and an improved PFS compared to CAR-T, including in pts with early treatment failure (within 12 months). These results are in line with previously reported improved clinical outcomes with auto-HCT compared to CAR-T in pts in partial remission (Shadman et al. Blood, 2022). The data support utilization of auto-HCT in pts with relapsed LBCL achieving a CR.

Fragmented care in localized pancreatic cancer: Is commission on cancer accreditation associated with improved overall survival?

BackgroundPrior studies of fragmentation of care in pancreatic cancer have not adjusted for indicators of hospital quality such as Commission on Cancer accreditation. The effect of fragmentation of care has not been well defined. MethodsWe queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy and distal pancreatectomy with perioperative systemic therapy for clinical stages I–III pancreatic cancer between 2006 and 2019. Patients who received systemic therapy at a center different than the center performing surgery were categorized as having fragmentation of care. Patients having fragmentation of care were further categorized on the basis of whether (fragmentation of care Commission on Cancer) or not (fragmentation of care non-Commission on Cancer) systemic therapy was administered at a facility accredited by the Commission on Cancer. ResultsA total of 11,732 patients met inclusion criteria; 5,668 (48.3%) underwent fragmentation of care, and 3,426 (29.2%) fragmentation of care non-Commission on Cancer. Patients undergoing fragmentation of care non-Commission on Cancer were less likely to receive neoadjuvant systemic therapy than those undergoing fragmentation of care Commission on Cancer or non-fragmented care (27.7% vs 40.1% vs 36.8%, P < .001). On Cox analysis, advanced age, comorbid disease, node-positive disease, and facility type were associated with risk of overall survival. Fragmentation of care was not (adjusted hazard ratio = 0.99, 95% confidence interval [0.94–1.06], P = .8). On Kaplan-Meier analysis, there were no significant differences in 5-year overall survival between treatment cohorts. ConclusionIn patients undergoing fragmentation of care for localized pancreatic cancer, those treated with systemic therapy in Commission on Cancer accredited facilities are more likely to be given neoadjuvant therapy but demonstrate no significant improvement in survival relative to those undergoing non-fragmented care or those undergoing fragmentation of care but receiving systemic therapy in nonaccredited facilities.

Impact of radiation therapy and alpha-fetoprotein level on survival outcomes for patients with hepatocellular carcinoma: a population-based study.

The use of radiation therapy (RT) in hepatocellular carcinoma (HCC) remains a matter for debate. Recently published research indicate that advanced RT techniques may improve survival in patients with HCC. This study aimed to evaluate this hypothesis in a large-scale retrospective cohort. The effect of alpha-fetoprotein (AFP) was taken into account because of its important role in the prognosis of HCC. The Surveillance, Epidemiology, and End Results (SEER) database was queried for adults patients diagnosed 2010-2019 with HCC (≥ 18 years). The study population was divided into four groups: Non-radiation & AFP-positive (reference), Non-radiation & AF-negative, Radiation & AFP-positive, Radiation & AFP-negative. Distant metastasis (DM) was used as a stratification factor. Differences in 5-year overall survival (OS) of the four groups were assessed using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards model were used to estimate unadjusted and adjusted hazard ratios (HR). A total of 34,656 patients were eligible for this analysis, including 21,084 (60.8%), 8,449 (24.4%), 3,810 (11.0%) and 1,313 (3.8%) in the Non-radiation & AFP-positive, Non-radiation & AF-negative, Radiation & AFP-positive and Radiation & AFP-negative groups, respectively. Median OSs of the four groups were 3, 4, 5 and 11 months in the DM cohort, and 12, 28, 15, and 28 months in the Non-DM cohort. Patients in the Radiation & AFP - group had the best OS and patients in the Non-radiation & AFP + group had the worst OS (adjusted HR [95% confidence interval (CI)]: 0.497 [0.399-0.619] in the DM cohort, and 0.405 [0.372-0.441] in the Non-DM cohort). Radiation & AFP + also showed improved survival compared with the reference group (adjusted HR [95%CI]: 0.725 [0.657-0.801] in the DM cohort, and 0.630 [0.600-0.661] in the Non-DM cohort). This population-based cohort study confirmed a significant improvement in overall survival with radiation therapy in HCC. AFP-negative patients benefit the most from RT. Superior OS of radiation therapy and AFP-negative status persisted even in patients with complex metastasis patterns. Our data suggest that radiation may provide an alternative modality for unresectable HCC.

SOX combined with sintilimab versus SOX alone in the perioperative management of locally advanced gastric cancer: a propensity score–matched analysis

ObjectivesTo evaluate the efficacy of SOX combined with a programmed cell death protein-1 (PD-1) inhibitor compared with SOX alone in the perioperative management of locally advanced gastric cancer and to explore biomarkers that may predict response to anti-PD-1 therapy.MethodsData of patients with clinical stage T3–4aN0–3M0 (IIb–III) gastric cancer were reviewed to create a primary database. Patients treated with perioperative SOX combined with sintilimab were included in Group A, while those treated with SOX alone were included in Group B. After one-to-one propensity score matching, pathological response and short-term survival outcomes were compared between the two groups. In addition, potential efficacy-related biomarkers were analyzed.ResultsBetween January 2018 and December 2022, a total of 150 patients were included in the analysis, with 75 patients in each group. The rates of pathological complete response (21.3% vs. 4.0%; P = 0.001) and major pathological response (45.3% vs. 22.7%; P = 0.003) in Group A were statistically higher than those in Group B. There was no significant difference in 1-year overall survival (92.8% vs. 92.0%; P = 0.392) and disease-free survival (88.9% vs. 88.0%; P = 0.357) between the two groups. Subgroup analysis of Group A showed that the pathological complete response (40.6% vs. 8.6%; P = 0.002) and major pathological response (65.6% vs. 28.6%; P = 0.002) rates were significantly higher in programmed death ligand-1-positive patients with a combined positive score of ≥ 5. A pathological complete response was achieved in 42.9% patients (3/7) with mismatch repair deficiency. For the two patients confirmed as Epstein-Barr virus-positive, one patient achieved a pathological complete response and the other achieved a major pathological response.ConclusionsThe adoption of SOX combined with a PD-1 inhibitor may improve the pathological response rate of patients with locally advanced gastric cancer, especially those with programmed death ligand-1 combined positive score ≥ 5, Epstein–Barr virus-positivity and mismatch repair deficiency. However, further prospective studies are still warranted to confirm the long-term survival benefit.