Comparison of biochemical changes induced in radioresistant prostate cancer cells by X-rays, radiosensitizing drugs, and a combined therapy using Raman microspectroscopy.

Cancer radioresistance is a major problem in radiotherapy. Many strategies have been proposed to overcome this process including the use of radiosensitizing drugs such as C75 or silibinin. The overall result of all treatments (radiotherapy, chemotherapy, and combined treatment) is cancer cell death. On the other hand, each treatment affects cancer cells differently at the molecular level. However, little is known about biochemical changes induced in cancer cells by these treatments (especially in combined therapy) at the submicroscale. In this study, Raman microspectroscopy was applied to follow such changes induced in radioresistant prostate cancer cells by X-rays, radiosensitizing drugs (C75, silibinin), and a combined treatment. The analysis was supported by the Partial Least Squares Regression method to reveal spectral changes induced by an increasing dose of X-rays and concentrations of the drugs. The obtained regression coefficient (ß) plots were compared to each other using a correlation coefficient (R). Our results show that PC-3 cells exhibit dose- and concentration-dependent responses to the treatment with different biochemical changes induced by X-rays in the presence of C75 and silibinin. Moreover, both drugs affect the cells differently at the submicroscale and independently from the X-ray's presence. Finally, C75 shows significant efficiency in the reduction of cell radioresistance.

Glofitamab in Relapsed/Refractory Mantle Cell Lymphoma: Results From a Phase I/II Study.

PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL. METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and 15 (10 mg) of cycle 1, with a target dose of 16 or 30 mg once every 3 weeks from cycle 2 day 1 onward, for 12 cycles. Efficacy end points included investigator-assessed complete response (CR) rate, overall response rate (ORR), and duration of CR. RESULTS: Of 61 enrolled patients, 60 were evaluable for safety and efficacy. Patients had received a median of two previous therapies (range, 1-5). CR rate and ORR were 78.3% (95% CI, 65.8 to 87.9) and 85.0% (95% CI, 73.4 to 92.9), respectively. In patients who had received previous treatment with a Bruton tyrosine kinase inhibitor (n = 31), CR rate was 71.0% (95% CI, 52.0 to 85.8) and ORR was 74.2% (95% CI, 55.4 to 88.1). CRS after glofitamab administration occurred in 70.0% of patients, with a lower incidence in the 2,000 mg (63.6% [grade ≥2, 22.7%]) versus 1,000 mg (87.5%; grade ≥2, 62.5%) Gpt cohort. Four adverse events led to glofitamab withdrawal (all infections). CONCLUSION: Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

Pre-Transplant Dual-Energy X-ray Absorptiometry (DXA)-Derived Body Composition Measures as Predictors of Treatment Outcomes and Early Post-Transplant Complications in Patients with Multiple Myeloma (MM) Treated with Autologous Hematopoietic Stem Cell Transplantation (AutoHSCT).

Background/Objectives: Changes in muscle mass and bone density are common in multiple myeloma (MM) patients. Dual-energy X-ray absorptiometry (DXA) offers precise, non-invasive insights into a patient's physical condition before autologous stem cell transplantation (autoHSCT). This study examines how pre-transplant body composition impacts treatment outcomes and early complications in MM patients undergoing autoHSCT. Methods: This study is a single-center, retrospective analysis of patients with MM who were treated with first or second autoHSCT and underwent DXA pre-transplant between 11 August 2019 and 12 June 2024. Results: We conducted a study of pre-transplant body composition in 127 patients with MM. Among them, 108 (85%) qualified for first autoHSCT, while 19 (15%) qualified for a second. The median age of the patients was 64 years (range 50-73). In the Cox proportional hazards regression conducted in the group of women, Total Body %Fat was a statistically significant predictor for progression-free survival (PFS) (HR = 0.07, 95% CI = 0.01,0.6, p = 0.0157). In the Mann-Whitney U test conducted on males, Lean Mass/Height2 and Appen. Lean Height2 were statistically significant predictors of early infections after autoHSCT (Z = 1.98, p = 0.0473 and Z = 2.32, p = 0.0204, respectively). In males, Fat Mass/Height2 was a significant predictor of non-infectious toxicity related to treatment (Z = -1.98, p = 0.0476). Conclusions: In women, higher levels of adipose tissue initially appear to exert a protective effect; however, this benefit diminishes over time, with greater fat mass eventually correlating with an increased risk of disease progression. In men, muscle mass has been identified as a significant predictor of early infection risk post-autoHSCT. Furthermore, our findings indicate that an increased amount of adipose tissue in men is statistically associated with a higher risk of non-infectious treatment-related toxicity. These conclusions highlight the critical need for further investigation into the role of body composition.

Increased abundance of Firmicutes and depletion of Bacteroidota predicts poor outcome in chronic lymphocytic leukemia.

Evidence indicates that there are significant alterations in gut microbiota diversity and composition in patients with hematological malignancies. The present study investigated the oral and intestinal microbiome in patients with chronic lymphocytic leukemia (CLL) (n=81) and age-matched healthy volunteers (HVs; n=21) using 16S ribosomal RNA next-generation sequencing. Changes in both oral and gut microbiome structures were identified, with a high abundance of Proteobacteria and depletion of Bacteroidetes in CLL as compared to HVs. Oral and stool samples of patients with CLL revealed a significant change in the abundance of short-chain fatty acid-producing genera in comparison with HVs. Furthermore, the relative abundance of oral and intestine Bacteroidetes was significantly decreased in patients with CLL with negative prognostic features, including unmutated immunoglobulin heavy chain gene (IGHV). Notably, an increased abundance of gut Firmicutes was found to be associated with high expression of CD38. Finally, the present study suggested the log Firmicutes/Bacteroidota ratio as a novel intestinal microbiome signature associated with a shorter time to first treatment in individuals with CLL. The findings indicate that oral and gut microbial diversity in CLL might point to the inflammatory-related modulation of the clinical course of the disease.

Soluble MICA concentrations and genetic variability of MICA and its NKG2D receptor as factors affecting Graft-versus-Host Disease development after allogeneic haematopoietic stem cell transplantation.

Despite new treatment strategies, graft-versus-host disease (GvHD) remains a formidable complication after allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the impact of polymorphisms and expression of MICA and NKG2D receptor on the development of GvHD in allogeneic HSCT recipients. Soluble MICA (sMICA) concentration was measured in serum collected 30 days after transplantation and the genetic variability of MICA and NKG2D genes was evaluated. The frequency of NKG2D+NK cells was determined by flow cytometry before and (21, 30, 60 and 90 days) after transplantation. Recipients with acute GvHD grades II-IV carried the NKG2D rs1049174 C allele more frequently than controls or patients with no or mild disease. Patients with chronic GvHD had higher frequency of NKG2D expressing NK cells posttransplant, reflecting increased activity of their NK cells. Although no direct relationship between MICA SNPs and GvHD were observed, the presence of MICA rs1051792 GG genotype correlated with elevated sMICA levels and increased serum level of sMICA was associated with higher risk of chronic GvHD. Our findings suggest that sMICA concentration may serve as a potential biomarker for chronic GvHD and emphasize the impact of genetic variability of NKG2D and its surface expression on the HSCT outcome.

Secondary Binding Site of CYP17A1 in Enhanced Sampling Simulations.

Androgens like testosterone and dihydrotestosterone play a key role in prostate cancer progression, making the enzyme CYP17A1, essential for androgen synthesis, a crucial therapeutic target. Recent studies have revealed electron density at the substrate entry channel, suggesting the presence of a secondary binding site. In this study, we calculated the binding free energy landscape of known ligands at this site using Funnel Metadynamics. Our results characterize this binding site and indicate that nonheme-interacting ligands could effectively bind to CYP17A1, providing a novel approach to the design of CYP17A1 inhibitors.

Compound Castings for the Coke Industry.

In this paper, issues related to the technology of compound castings composed of two parts, i.e., the working layer and the supporting part, made of X46Cr13 high-chromium steel and EN-GJL-HB 255 grey cast iron, respectively, in a liquid-solid system by pre-installing a monolithic insert in the mould cavity are presented. As a part of the research, the mechanism of formation of transitional zones in the bonding area of the above-mentioned two alloys was identified and described. It was shown that the phenomenon that determines the formation of a permanent bond between the joined materials is the transport of C and heat from the "high-carbon and hot" material of the supporting part poured into the mould in the form of liquid cast iron to the "low-carbon and cold" material of the working layer placed in the form of a steel monolithic insert inside the mould cavity. In the paper, the suitability of the compound castings technology developed for use in the coke industry is also presented. Full-size high-chromium steel-grey cast iron compound casting plates designed for the coke quenching car lining were positively verified in real coke plant operating conditions.

Unravelling the potential of TIM-3 gene polymorphism in allogeneic hematopoietic stem cell transplantation - a preliminary study.

BACKGROUND: T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) molecule is a key regulator of the immune response by exerting an inhibitory effect on various types of immune cells. Understanding the role of TIM-3 in hematopoietic stem cell transplantation (HSCT) may improve transplant outcomes. Our study evaluated the potential association between TIM-3 polymorphisms, namely rs1036199 (A > C) or rs10515746 (C > A), changes which are located in exon 3 and the promoter region of the TIM-3 gene, and post-HSCT outcomes. METHODS: One-hundred and twenty allogeneic HSCT patients and their respective donors were enrolled and genotyped for TIM-3 single nucleotide polymorphisms (SNPs) using real-time PCR with TaqMan assays. RESULTS: We found that the presence of the rare alleles and heterozygous genotypes of studied SNP in recipients tended to protect against or increase the risk for acute graft-versus-host disease (aGvHD). For the rs1036199 polymorphism, recipients with the AC heterozygous genotype (p = 0.0287) or carrying the rarer C allele (p = 0.0334) showed a lower frequency of aGvHD development along all I-IV grades. A similar association was detected for the rs10515746 polymorphism as recipients with the CA genotype (p = 0.0095) or the recessive A allele (p = 0.0117) less frequently developed aGvHD. Furthermore, the rarer A allele of rs10515746 SNP was also associated with a prolonged aGvHD-free survival (p = 0.0424). Cytomegalovirus (CMV) infection was more common in patients transplanted with TIM-3 rs10515746 mismatched donors (p = 0.0229) and this association was also found to be independent of HLA incompatibility and pre-transplant CMV-IgG status. Multivariate analyses confirmed the role of these recessive alleles and donor-recipient TIM-3 incompatibility as an independent factor in aGvHD and CMV development. CONCLUSIONS: Polymorphism of TIM-3 molecule may affect the immune response in HSCT patients. The recessive alleles of rs1036199 and rs10515746 SNPs decreased the risk of developing aGvHD. TIM-3 donor-recipient genetic matching may also affect the risk of post-transplant CMV infection, indicating the potential value of genetic profiling in optimizing transplant strategies.

MICB Genetic Variants and Its Protein Soluble Level Are Associated with the Risk of Chronic GvHD and CMV Infection after Allogeneic HSCT.

The aim of the present study was to determine the associations between the MICB genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two MICB polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the MICB rs1065075 G allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% vs. 65.38%, p = 0.046). Moreover, the MICB rs1065075 G allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (p = 0.015) and as a recipient allele (p = 0.039). The MICB rs1065075 G variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (p = 0.0386) and cGvHD (p = 0.0008) compared to recipients without those complications. A protective role of the G allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% vs. 69.23%; p = 0.013). MICB genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.

A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience.

Introduction: Mixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the "know-how" of MPAL is based only on retrospective analyses performed on small groups of patients. Materials and methods: In this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed. Results: Sixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16-24) and 17 days (range, 12-24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes. Conclusions: CLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control.

Sinus bradycardia as a rare adverse event in patients receiving cyclosporine A after allogeneic hematopoietic stem cell transplantation.

Cyclosporine A (CSA) is a commonly used immunosuppressive agent for the prophylaxis of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (alloHSCT). While tachycardia is a known adverse effect of CSA, bradycardia remains a phenomenon rarely described in the literature. We conducted a retrospective evaluation of the incidence of bradycardia in patients after alloHSCT treated with CSA between January 2020 and February 2023 at our center. Out of 206 patients, sinus bradycardia following the administration of CSA was observed in 6 (2.9%), comprising 3 women and 3 men, with the median age of 55 years (range: 20-65). The underlying diseases were myeloid malignancies in 4 and aggressive lymphoma in 2 patients. The patients received grafts from a matched unrelated (n=5) or a haploidentical family donor (n=1) following various conditioning regimens. Coexisting cardiovascular disorders were found in 5 of the 6 patients. All patients experienced symptomatic bradycardia within 1-4 days (median 2 days) after CSA introduction, which persisted until CSA withdrawal. One patient required treatment with atropine. All patients continued their immunosuppressive therapy with tacrolimus, which was well-tolerated Our study indicates CSA as a causative factor of sinus bradycardia in a small percentage of alloHSCT patients receiving CSA as graft-versus host disease (GvHD) prophylaxis. Importantly, these patients did not experience any cardiac complications when switched to tacrolimus. Although further research on the effects of CSA on heart automatation is needed, our single-center experience can help prompt diagnosis and therapeutic intervention in daily clinical practice.

Mass spectrometry-based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma.

ABSTRACT: Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in the PB in the posttransplant setting, despite unavailability of pretreatment calibration samples. There was high agreement between MRD by MS in the PB and paired bone marrow (BM) MRD results at the 10-5 threshold, assessed by either next-generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which, in landmark analysis, reached statistical significance after 18 cycles after transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared with MRD negativity by only 1 modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, posttransplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293.

Improving the Abrasion Resistance of Nodular Cast Iron Castings by Remelting Their Surfaces by Laser Beam.

This paper presents the results of research conducted in the field of the technology of surface hardening of castings from unalloyed and low-alloy nodular cast iron using the laser remelting method. The range of studies included macro- and microhardness measurements using Rockwell and Vickers methods as well as metallographic microscopic examinations using a scanning electron microscope. Moreover, abrasive wear resistance tests were performed using the pin-on-disk method in the friction pair of nodular cast iron-SiC abrasive paper and the reciprocating method in the friction pair of nodular cast iron-unalloyed steel. Analysis of the test results shows that the casting surface layer remelting by laser for unalloyed nodular cast iron results in a greater improvement in its resistance to abrasive wear in the metal-mineral system, as compared to low-alloy cast iron. Additionally, carrying out the laser hardening treatment of the surface layer made of the tested grades of nodular cast iron is justified only if the tribological system of the cooperating working parts and allowable dimensional changes during their operation are known.

Fast cancer imaging in pancreatic biopsies using infrared imaging.

Pancreatic cancer, particularly Pancreatic ductal adenocarcinoma, remains a highly lethal form of cancer with limited early diagnosis and treatment options. Infrared (IR) spectroscopy, combined with machine learning, has demonstrated great potential in detecting various cancers. This study explores the translation of a diagnostic model from Fourier Transform Infrared to Quantum Cascade Laser (QCL) microscopy for pancreatic cancer classification. Furthermore, QCL microscopy offers faster measurements with selected frequencies, improving clinical feasibility. Thus, the goals of the study include establishing a QCL-based model for pancreatic cancer classification and creating a fast surgical margin detection model using reduced spectral information. The research involves preprocessing QCL data, training Random Forest (RF) classifiers, and optimizing the selection of spectral features for the models. Results demonstrate successful translation of the diagnostic model to QCL microscopy, achieving high predictive power (AUC = 98%) in detecting cancerous tissues. Moreover, a model for rapid surgical margin recognition, based on only a few spectral frequencies, is developed with promising differentiation between benign and cancerous regions. The findings highlight the potential of QCL microscopy for efficient pancreatic cancer diagnosis and surgical margin detection within clinical timeframes of minutes per surgical resection tissue.

High-definition FT-IR reveals a synergistic effect on lipid accumulation in prostate cancer cells induced by a combination of X-rays and radiosensitizing drugs.

Radiotherapy is one of the most commonly used cancer therapies with many benefits including low toxicity to healthy tissues. However, a major problem in radiotherapy is cancer radioresistance. To enhance the effect of this kind of therapy several approaches have been proposed such as the use of radiosensitizers. A combined treatment of radiotherapy and radiosensitizing drugs leads to a greater effect on cancer cells than anticipated from the addition of both responses (synergism). In this study, high-definition FT-IR imaging was applied to follow lipid accumulation in prostate cancer cells as a response to X-ray irradiation, radiosensitizing drugs, and a combined treatment of X-rays and the drugs. Lipid accumulation induced in the cells by an increasing X-ray dose and the presence of the drugs was analyzed using Principal Component Analysis and lipid staining. Finally, the synergistic effect of the combined therapy (X-rays and radiosensitizers) was confirmed by calculations of the integral intensity of the 2850 cm-1 band.

The comparison of safety and cost between reference drug of rituximab and its biosimilar Riximyo in lymphoproliferative disorders and other hematological diseases. Single center experience.

Rituximab, anti-CD20 monoclonal antibody, has broad clinical application. The aim of this study is to compare the safety and cost of the original reference rituximab (MabThera) and its biosimilar (Riximyo). This retrospective analysis of 262 patients receiving Riximyo in the Department of Hematology of Wroclaw Medical University in Poland from the period of 1 October 2020 to 21 June 2021 focused on infusion-related reactions (IRRs), which occurred in 4,96% of patients (N = 13). 109 patients (41,6%) had previously been treated with the reference drug and 2 IRRs were reported after switching therapy. During the study period, after biosimilar introduction, the cost of rituximab decreased by 41%. Rixmyo while maintaining similar safety profile is much more cost-effective.

Association of bone mineral density and potential risk factors for osteoporosis in patients with severe haemophilia A.

INTRODUCTION: In people with haemophilia (PWH), recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effects of various other factors on bone mineral density (BMD) reduction have found conflicting results. AIM: The aim of this study was to analyse the relationships between BMD, bone mineral content (BMC), and trabecular bone score (TBS) parameters based on the dual X-ray absorptiometry method (DXA) and potential risk factors for osteoporosis in patients with severe haemophilia A. METHODS: Fifty-five men with severe haemophilia A, aged 18-68 years, and 59 healthy volunteer men were enrolled in this study. Densitometric-derived lumbar spine and femoral neck BMD, BMC, and TBS were measured. Blood analyses were performed for morphology parameters, liver and kidney function parameters, and viral status. Serum levels of oestradiol (E2 ), testosterone (T), dehydroepiandrosterone sulphate (DHEA-S), parathormone, and vitamin D were measured. RESULTS: Patients showed significantly lower BMD compared to controls (p < .003). The result below the expected range for age was nearly double (6.82% vs. 3.92%) in PWH under 50 years old compared to controls. Haemophilic patients also exhibited significantly higher vitamin D3 deficiency (p < .0001), which was strongly associated with low TBS. Additionally, low body mass index and high neutrophil/lymphocyte ratio were correlated with low BMC and BMD. CONCLUSIONS: This study confirms the prevalence of low BMD and BMC in patients with haemophilia in Poland. Factors that contribute to low BMD are primarily vitamin D deficiency, low BMI, high neutrophil/lymphocyte ratio, and low testosterone/oestradiol ratio.

Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).

Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1.

Pancreatic intraepithelial neoplasia detection and duct pathology grading using FT-IR imaging and machine learning.

Pancreatic intraepithelial neoplasia (PanIN) is manifested by noninvasive lesions in the epithelium of smaller pancreatic ducts. Generally, cancer development risk from low-grade PanIN is minor, whereas, invasive pancreatic ductal adenocarcinoma (PDAC) development is highly related to high-grade PanINs. Therefore, in the case of high-grade PanIN detection, additional surgical resection may be recommended. However, even the low-grade PanINs can indicate possible progression to PDAC. The definition of PanIN is constantly changing and there is a need for new tools to better characterize and understand its behavior. We have recently developed a comprehensive pancreatic cancer classification model with biopsies collected from over 600 biopsies from 250 patients. Here, we take the next step and employ Infrared (IR) spectroscopy to build the first classification model for PanINs detection. Furthermore, we created a Partial Least Squares Regression (PLSR) model to characterize ducts from benign to cancerous. This model was then used to predict and grade PanINs accordingly to their malignancy level.