The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study.

BACKGROUND: Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer. METHODS: This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias. RESULTS: Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002). CONCLUSIONS: Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.

Chemoresistance in acute myeloid leukemia: An alternative single-cell RNA sequencing approach.

Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This study aimed to identify potential mechanisms of chemoresistance of the "7 + 3" induction in AML by using a single-cell RNA sequencing (scRNA-seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non-CR (n = 5). Single-cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA-seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell-like cells from the non-CR group expressed more leukemic stem cell markers (CD9, CD82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA-seq and bulk RNA-seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the "7 + 3" induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA-seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.

The JMJD6/HURP axis promotes cell migration via NF-κB-dependent centrosome repositioning and Cdc42-mediated Golgi repositioning.

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA-associated acetyl-tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6-guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6-induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF-κB-induced CR and subsequently CR-dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF-κB-CR-Cdc42 cascade collectively dictate GR.

Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia.

Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.

Cytomegalovirus in the transplant setting: Where are we now and what happens next? A report from the International CMV Symposium 2021.

The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV-specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity have led to improved patient outcomes. In the future, management algorithms may be individualized based on the transplant recipient's immune profile, which will mark the start of a new era for patients with CMV.

Investigating early progression of Hodgkin lymphoma in a two-center analysis.

BACKGROUND/PURPOSE: The early progression of disease (POD) of Hodgkin lymphoma (HL) leads to a poor prognosis. To identify risk factors for early POD, this retrospective two-center cohort analysis was conducted. METHODS: Medical records of HL patients between 1998 and 2020 from two referral centers were reviewed. RESULTS: Two-hundred and sixty-nine patients were analyzed. The distribution of early vs. advanced stages was 51.1 vs. 48.9%, respectively. The 5-year progression free survival (PFS) was 63%, and the overall survival (OS) was 87% with a median follow-up of 52.0 months. The complete remission (CR) rate was 85.7%. Disease progression or relapsed disease occurred in 33.9% (n = 85) of patients while 17.0% of this cohort had early POD within 12 months of induction therapy. Patients with early POD had a worse median OS than those without (p < 0.001). Failure to achieve post-induction CR and high international prognostic score (IPS, 3-7) were independent risk factors for early POD. Compared with chemotherapy alone, consolidative radiotherapy after induction chemotherapy was associated with a lower risk of early POD (21.3% vs. 6.2%, p = 0.006). CONCLUSION: High IPS was an independent risk factor for early POD, which was less observed in those with consolidative radiotherapy.

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

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

Risk factors for nonresponsive hydration in patients with spinal cerebrospinal fluid leakage.

BACKGROUND: Spinal cerebrospinal fluid (CSF) leakage is frequently encountered clinically after lumbar puncture or spontaneous events. Although some patients recover without treatment or after intensive hydration, some require an epidural blood patch (EBP). The risks of nonresponsive hydration remain unknown. Therefore, we identified the risk factors for patients with spinal CSF leakage nonresponsive to hydration. METHODS: We retrospectively reviewed patients diagnosed with spinal CSF leakage between January 2010 and March 2021. Clinical data, including patient age, sex, etiology, and radiological indications in magnetic resonance imaging, were compared between patients who were responsive and non-responsive to hydration. RESULTS: Of the 74 patients with spinal CSF leakage, 25 were responsive to hydration and 49 required EBP. Patients who were nonresponsive to hydration were older (39.27 vs. 34.32 years, P = 0.01), had a higher percentage of spontaneous intracranial hypotension (93.88% vs. 68.00%, P = 0.005), had more spinal CSF leakage (12.04 vs. 8.04, P = 0.01), and had a higher percentage of dural sinus engorgement (81.63% vs. 60.00%, P = 0.044). Spontaneous intracranial hypotension (odds ratio [OR]: 4.63; 95% confidence interval [CI]: 1.00-21.38) and having ≥9 spinal CSF leakages (OR: 3.29; 95% CI: 1.08-10.01), as indicated by magnetic resonance myelography, are considered risk factors for noneffective hydration. CONCLUSIONS: Patients with spinal CSF leakage who have spontaneous intracranial hypotension and those with ≥9 spinal CSF leakages are considered at risk for noneffective hydration. EBP should be considered early in these patients.

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

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

Integrating resistance functions to predict response to induction chemotherapy in de novo acute myeloid leukemia.

OBJECTIVES: This study explored resistance functions and their interactions in de novo AML treated with the "7 + 3" induction regimen. METHODS: We analyzed RNA-sequencing profiles of whole bone marrow samples from 52 de novo AML patients who completed the "7 + 3" regimen and stratified patients into CR (n = 35) and non-CR (n = 17) groups. RESULTS: A systematic gene set analysis revealed significant associations between chemoresistance and mTOR (P < .001), myc (P < .001), mitochondrial oxidative phosphorylation (P < .001), and stemness (P = .002). These functions were independent with regard to gene contents and activity scores. An integration of these four functions showed a prediction of chemoresistance (area under the receiver operating characteristic curve = 0.815) superior to that of each function alone. Moreover, our proposed seven-gene scoring system significantly correlated with the four-function model (r = .97; P < .001) to predict chemoresistance to the "7 + 3" regimen. On multivariate analysis, a seven-gene score of ≥-0.027 (hazard ratio: 11.18; 95% confidence interval: 2.06-60.65; P = .005) was an independent risk factor for induction failure. CONCLUSIONS: Myc, OXPHOS, mTOR, and stemness were responsive for chemoresistance in AML. Treatments other than the "7 + 3" regimen need to be considered for de novo AML patients predicted to be refractory to the "7 + 3" regimen.

Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia.

BACKGROUND: Owing to the shortage of hematopoietic stem cells from matched sibling donors (MSD) and matched unrelated donors (MUD), the number of patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) has rapidly increased. Despite a comparable overall survival (OS) and leukemia-free survival using this approach, some evidence suggests that haploidentical allo-HSCT recipients have a higher incidence of cytomegalovirus (CMV) infection, though this has not been clearly established. METHODS: This study retrospectively compared the cumulative incidence of CMV DNAemia, 2-year OS, and leukemia-free survival rates in acute leukemia patients with MSD (n = 41), MUD (n = 18), and haploidentical donor allografts (n = 21). RESULTS: The cumulative incidences of CMV DNAemia at day 180 in the MSD, MUD, and haploidentical groups were 39.0, 55.6, and 85.7%, respectively (P < 0.000). As less than 50% of patients in the MSD group were detected to have CMV DNAemia, the median time to CMV DNAemia detection in patients allografted with MSD could not be obtained. However, it was 42 and 29 days, respectively, for the MUD and haploidentical groups. Multivariate analysis revealed that haploidentical allo-HSCT (MSD vs. haploidentical: HR: 0.26; 95% CI: 0.09-0.78; P = 0.017) and age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.011) increased CMV infection. Finally, MSD, MUD, and haploidentical allo-HSCT provided comparable 2-year OS rates (52.1%, 65.5%, and 65.6%; P = 0.425) and 2-year leukemia-free survival rates (67.1%, 68.3%, and 80.7%, P = 0.837). CONCLUSION: The CMV incidence was higher for haploidentical allo-HSCT than for MSD and MUD allo-HSCT; this could be explained by graft-versus-host disease prophylaxis by multiple immunosuppressants.

Future Aspects of CDK5 in Prostate Cancer: From Pathogenesis to Therapeutic Implications.

Cyclin-dependent kinase 5 (CDK5) is a unique member of the cyclin-dependent kinase family. CDK5 is activated by binding with its regulatory proteins, mainly p35, and its activation is essential in the development of the central nervous system (CNS) and neurodegeneration. Recently, it has been reported that CDK5 plays important roles in regulating various biological and pathological processes, including cancer progression. Concerning prostate cancer, the androgen receptor (AR) is majorly involved in tumorigenesis, while CDK5 can phosphorylate AR and promotes the proliferation of prostate cancer cells. Clinical evidence has also shown that the level of CDK5 is associated with the progression of prostate cancer. Interestingly, inhibition of CDK5 prevents prostate cancer cell growth, while drug-triggered CDK5 hyperactivation leads to apoptosis. The blocking of CDK5 activity by its small interfering RNAs (siRNA) or Roscovitine, a pan-CDK inhibitor, reduces the cellular AR protein level and triggers the death of prostate cancer cells. Thus, CDK5 plays a crucial role in the growth of prostate cancer cells, and AR regulation is one of the important pathways. In this review paper, we summarize the significant studies on CDK5-mediated regulation of prostate cancer cells. We propose that the CDK5-p35 complex might be an outstanding candidate as a diagnostic marker and potential target for prostate cancer treatment in the near future.

Transcriptional repression of Aurora-A gene by wild-type p53 through directly binding to its promoter with histone deacetylase 1 and mSin3a.

In this study, we firstly showed that p53 transcriptionally represses Aurora-A gene expression through directly binding to its promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay indicated that p53 physically bound to the Aurora-A promoter. Moreover, the in vitro and in vivo assays showed that p53 directly bound to the Aurora-A promoter together with histone deacetylase 1 (HDAC1) and mSin3a as corepressors. Furthermore, we identified that the nucleotides -360 to -354 (CCTGCCC), upstream of the Aurora-A transcriptional start site, was responsible for the p53-mediated repression. Mutation within this site disrupted its interaction with p53, mSin3a and HDAC1, as well as attenuated the repressive effect of p53 on Aurora-A promoter activity. Treatment with trichostatin A (TSA), a HDAC1 inhibitor, disrupted the interaction of p53-HDAC1-mSin3a complex with the nucleotides -365∼-345 region, and enhanced the Aurora-A promoter activity and gene expression. Additionally, knockdown of p53 or mSin3a also drastically blocked the formation of p53-HDAC1-mSin3a repressive complex onto this promoter region and elevated the Aurora-A promoter activity and gene expression. Moreover, the p53-HDAC1-mSin3a repressive complex also involved in the inhibition of Aurora-A gene expression upon cisplatin treatment. Finally, the clinical investigation showed that Aurora-A and p53 exhibited an inverse correlation in both the expression level and prognostic status, and the low p53/high Aurora-A showed the poorest prognosis of NSCLC patients. Our findings showed novel regulatory mechanisms of p53 in regulating Aurora-A gene expression in NSCLC cells.

Liver resection for hepatocellular carcinoma in patients with hematological malignancies.

BACKGROUND: Improvements in antimetabolite drugs have prolonged the survival of patient with hematological malignancies. However, these drugs may have hepatotoxic side effects and may induce acute liver failure, chronic liver fibrosis, cirrhosis, or even hepatocellular carcinoma (HCC). Although liver resection remains a curative option for HCC, its role in HCC with hematological malignancies has never been fully explored. METHODS: A retrospective review of 1725 patients who underwent curative liver resection for newly diagnosed HCC between 1994 and 2016 was conducted. Among these patients, 16 had a history of hematological malignancies (HM group). Their hematological malignancies were well-controlled at the time of liver resection. The clinicopathological characteristics of the HM group, along with their short- and long-term outcomes after liver resection, were compared with those of the other 1709 patients without hematological malignancy (non-HM group). RESULTS: All HM group patients were seropositive for hepatitis marker surface for hepatitis B and C. No significant differences were observed in any background characteristics between the two groups. The postoperative complication rate and 90-day mortality in the HM and non-HM groups were 25 and 20.4%, P = 0.754, and 0 and 0.6%, P = 1.000, respectively. The 5-year disease-free and overall survival rates for the HM and non-HM groups were 42.3 and 35.1%, P = 0.552, and 69.5 and 56.9%, P = 0.192, respectively. CONCLUSIONS: Hepatitis markers should be examined during chemotherapy for hematological malignancies. Regular liver imaging studies are recommended for seropositive cases. When HCC occurs secondary to a well-controlled hematological malignancy, liver resection is suggested in selected patients.

Oncogenic roles of carbonic anhydrase 8 in human osteosarcoma cells.

Carbonic anhydrase 8 (CA8), a member of the carbonic anhydrase family, is one of the three isozymes that do not catalyze the reversible hydration of carbon dioxide due to the lack of one important histidine. In the present study, we observed increased expression of CA8 in more aggressive types of human osteosarcoma (OS) cells and found that CA8 expression is correlated with disease stages, such that more intense expression occurs in the disease late stage. We also demonstrated that overexpression of CA8 in human OS (HOS) cells significantly increased cell proliferation both in vitro and in vivo. Downregulated CA8 sensitized cells to apoptotic stress induced by staurosporine and cisplatin, suggesting a specific role of CA8 to protect cells from stresses. In addition, downregulation of CA8 in HOS cells reduced cell invasion and colony formation ability in soft agar and further decreased matrix metalloproteinase 9 and focal adhesion kinase expression, indicating that CA8 might facilitate cancer cell invasion via the activation of FAK-MMP9 signaling. Interestingly, HOS cells with CA8 knockdown showed a significant decrease in glycolytic activity and cell death under glucose withdrawal, further indicating that CA8 may be involved in regulating aerobic glycolysis and enhancing cell viability. Knockdown of CA8 significantly decreased phosphorylated Akt expression suggesting that the oncogenic role of CA8 may be mediated by the regulation of Akt activation through p-Akt induction. Importantly, the inhibition of glycolysis by 2-deoxyglucose sensitized CA8 HOS-CA8-myc cells to cisplatin treatment under low glucose condition, highlighting a new therapeutic option for OS cancer.

Outcome and late effects among acute myeloid leukemia survivors: a nationwide population-based study.

BACKGROUND: Understanding of pathogenesis and treatment for acute myeloid leukemia (AML) is growing. However, studies regarding the outcomes and late effects among AML survivors are relatively limited. METHODS: This nationwide population-based study used medical records from the Taiwanese National Health Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to 2008 were analyzed. The physiological and psychological morbidities in AML survivors were compared to those identified from a normal population. This study also compared late effects among AML survivors treated by intensive chemotherapy alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT). RESULTS: The incidence of AML in Taiwan has increased from 1.07 per 100,000 persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study cohort received best supportive care alone. Compared to the normal population, AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 % confidence interval [CI] 1.18-2.42; p < 0.01), cardiovascular disease (HR 2.53; 95 % CI 1.39-4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48-3.48; p < 0.001), and psychological disorders (HR 1.45; 95 % CI 1.04-2.04; p < 0.05). Although patients undergoing allo-HSCT had a better OS than did patients treated with intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001), diabetes was found more often among allo-HSCT recipients than among patients receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21-7.08; p < 0.05). CONCLUSION: Regular physical and psychological surveillance of AML survivors is needed especially for those receiving allo-HSCT.

Palonosetron versus first-generation 5-hydroxytryptamine type 3 receptor antagonists for emesis prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation.

First-generation 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists (RAs) are currently the standard of care for prophylaxis against allo-HSCT-induced emesis. However, the efficacy of this combination in allo-HSCT recipients is not entirely satisfying. We sought to compare the efficacy of first-generation 5-HT3 RAs with that of second-generation 5-HT3 RAs in emesis prevention in allo-HSCT recipients. A total of 51 consecutive patients undergoing allo-HSCT for various hematological diseases in our institution were retrospectively reviewed. Patients who received daily first-generation 5-HT3 RAs, and 60-h palonosetron for emesis prophylaxis were stratified into the standard (n = 23) and palonosetron (n = 28) groups, respectively. Emesis severity and rescue therapy requirements in patients between these two groups were compared. Our results showed patients in standard and palonosetron groups had comparable severity of both acute and delayed emesis. However, 52.2 % of the patients in the standard group required rescue therapy, compared to only 21.4 % of the patients in the palonosetron group (p = 0.046). Subgroup analysis showed rescue therapy for acute emesis was required by 26.1 % of the patients in the standard group and by only 3.6 % of the patients in the palonosetron group (p = 0.037). In conclusion, palonosetron and first-generation 5-HT3 RAs were at least equally effective in emesis prophylaxis for allo-HSCT recipients. Patients receiving palonosetron, especially for acute emesis, required rescue therapy less frequently than those receiving first-generation 5-HT3 RAs.

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

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