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Zymeworks Announces New Director Nominee

VANCOUVER, British Columbia, Oct. 16, 2023 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing novel multifunctional biotherapeutics, today announced that its board of directors will nominate Dr. Nancy Davidson for election to its board of directors at the Company’s upcoming annual general meeting of stockholders to be held on December 7, 2023.

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Zymeworks Announces New Director Nominee

Titan Pharmaceuticals Announces Appointment of Dato’ Seow Gim Shen and Brynner Chaim to the Company’s Board of Directors

SAN FRANCISCO, Oct. 16, 2023 (GLOBE NEWSWIRE) -- Titan Pharmaceuticals, Inc. (NASDAQ: TTNP) ("Titan" or the "Company") is pleased to announce the appointments of Dato’ Seow Gim Shen and Brynner Chiam to the Company’s Board of Directors, effective October 12, 2023. Mr. Shen has also been appointed Chairman of the Board.

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Titan Pharmaceuticals Announces Appointment of Dato' Seow Gim Shen and Brynner Chaim to the Company's Board of Directors

Jay Glazer Teams Up with Supernus Pharmaceuticals to Raise Awareness of ADHD and his Qelbree® Journey

ROCKVILLE, Md., Oct. 16, 2023 (GLOBE NEWSWIRE) -- Television personality and sports reporter Jay Glazer is opening up about his personal experiences with attention-deficit/hyperactivity disorder (ADHD) – one of the most common psychiatric diagnoses affecting approximately 10 million adults in the U.S. – and with Qelbree (viloxazine extended-release capsules), a nonstimulant medication for the treatment of ADHD.3

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Jay Glazer Teams Up with Supernus Pharmaceuticals to Raise Awareness of ADHD and his Qelbree® Journey

Apollomics Announces Presentations of Vebreltinib Data at ESMO 2023

FOSTER CITY, Calif., Oct. 16, 2023 (GLOBE NEWSWIRE) -- Apollomics Inc. (Nasdaq: APLM) (the “Company”), a late-stage clinical biopharmaceutical company developing multiple oncology drug candidates to address difficult-to-treat and treatment-resistant cancers, today announced that two abstracts detailing vebreltinib data were made available as part of the European Society of Medical Oncology Congress (ESMO) 2023 being held in Madrid, Spain from October 20-24, 2023.

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Apollomics Announces Presentations of Vebreltinib Data at ESMO 2023

Brother-in-law of surf industry fixture who died on medical retreat … – BeachGrit

Ire in the autumn air.

It is October in America, that time of year when Laird Superfood Pumpkin Spice fills the air and baseball the soul. Yes, while the World Surf League may claim to be the nations pastime, baseball has long occupied that slot. The season, which kicks off in spring, consists of 162 games winding through the dog days of summer and culminating in autumn.

The Fall Classic.

Now, in times past, the top three teams from each of the three division, both National and American Leagues, punched their playoff ticket to the playoffs alongside the National and American League team with the best record that didnt win its division as wildcards.

The Major League Baseball powers that be, though, wanted to add some spice and expanded the wildcard portion, allowing a few more teams a shot at the Big Dance. These teams play a three game series, then the winner plays the team with the best record in its league.

This tinkering has been compared to the World Surf Leagues decision to implement Finals Day wherein the top five surfers, male and female, head to Lower Trestles to compete in a winner-take-all showdown.

While the intention was to increase excitement in both baseball and surfing, the results have also benefited upstarts that just so happened to get hot.

Take Stephanie Gilmores worst-to-first 2022 performance in which Carissa Moore, the champion all year, was unseated.

Or, over on the baseball side, the Arizona Diamondbacks sweeping the Los Angeles Dodgers even though the Dodgers were ahead of the D-Backs by sixteen games at season end.

Last year, the Dodgers were undone by the San Diego Padres in similar fashion, leaving Dodger fans furious and wanting the playoff format changed back to the way it was.

Furious.

Message boards and op-eds are filled with salty messages from Dodgers, and Braves, fans decrying the Carissa Moore-ing of teams that proved their worth all season only to get Lower Trestled.

Surf fans not named Richard Toledo nodding quietly.

Will the grousing lead to changes?

Do you have thoughts on the matter or a horse in the race?

The Texas Rangers take on the Houston Astros tonight for the American League pennant.

All action, no lulls.

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Brother-in-law of surf industry fixture who died on medical retreat ... - BeachGrit

Faeth Therapeutics Announces National Academy of Medicine … – BioSpace

AUSTIN, Texas--(BUSINESS WIRE)-- Faeth Therapeutics, a leader in metabolic oncology research and treatment innovation, proudly announces the induction of its co-founder, Dr. Siddhartha Mukherjee, Assistant Professor at Columbia, Pulitzer Prize Winner, and one of Time 100's Most Influential People, into the esteemed National Academy of Medicine (NAM).

Dr. Mukherjee was honored for contributing important research in the immunotherapy of myeloid malignancies, such as Acute Myeloid Leukemia, for establishing international centers for immunotherapy for childhood cancers, and for the discovery of tissue-resident stem cells. His book, The Emperor of All Maladies, won the Pulitzer Prize and was nominated by Time as among the centurys 100 most influential books, introducing millions to modern cancer research. This recognition accentuates the collective dedication and caliber of Faeth's team and the company's commitment to advancing the realm of cancer care.

With Dr. Mukherjee's recent induction into the National Academy of Medicine, he joins fellow Faeth co-founders who have previously received this honor from the National Academy of Science: Karen Vousden, PhD, Chief Scientist of CRUK, Group Leader at the Crick Institute, and Director at Bristol Myers Squibb; Lew Cantley, PhD, Professor of Cell Biology at the Dana Farber Cancer Institute at Harvard University; Greg Hannon, PhD, Director of CRUK Cambridge Institute; and Scott Lowe, PhD, Chair of Cancer Biology & Genetics at Memorial Sloan Kettering, underlining the depth of Faeth Therapeutics' commitment to scientific excellence and innovation.

"Dr. Mukherjee's induction into the National Academy of Medicine reaffirms Faeth Therapeutics' dedication to unparalleled scientific rigor and innovation. We are immensely proud to have such an impressive team of co-founders driving our mission to redefine and elevate standards in oncology care," said Anand Parikh, J.D., Chief Executive Officer of Faeth Therapeutics.

Mukherjee is one of 100 new members announced by the academy. In the National Academy of Medicine, members are elected by their colleagues as a testament to their exceptional accomplishments. Being inducted into the academy represents one of the most prestigious accolades within the realm of medicine.

About Faeth Therapeutics

Faeth Therapeutics is a clinical-stage biotechnology company focused on bringing breakthrough research in metabolic oncology into the clinic. The company leverages its machine-learning platform to identify therapeutic programs that combine traditional therapeutics and a dietary metabolic regimen to enhance outcomes, with the goal of transforming the treatment landscape. Lead asset, FTH-001, combines serabelisib and an insulin-suppressing regimen to slow tumor growth via PI3K pathway inhibition. Faeths scientific founders include industry leaders Drs. Lew Cantley, Sid Mukherjee, Karen Vousden. For additional information, visit http://www.faeththerapeutics.com.

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Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace

Regulation of dermal fibroblasts by human neutrophil peptides … – Nature.com

Materials

The following reagents were used in this study: HNP1, HNP2 and HNP3 (Peptide Institute, Inc., Japan); TGF- (BioLegend Inc., CA, USA); Dulbeccos Modified Eagles Medium (Cytiva, Marlborough, MA, USA); Fetal Bovine Serum (Gibco, Grand Island, NY); ProLong Gold Antifade Mountant with DAPI (Invitrogen, CA, USA); LDH-Cytotoxicity Colorimetric Assay Kit II (BioVision Inc., CA, USA); RNeasy Mini Kit (QIAGEN Inc., Hilden, Germany); iScript Reverse Transcription Supermix, SsoAdvanced Universal Probes Supermix (Bio-Rad Inc., CA, USA); Pierce BCA Protein Assay Kit (Thermo Fisher Scientific Inc., NY, USA); 1X Protease/Phosphatase Inhibitor Cocktail, Rabbit anti-COL1A1 antibody, Mouse anti-Ki-67 antibody, Rabbit anti--actin antibody, Mouse anti-rabbit IgG antibody (HRP conjugate), Anti-rabbit IgG Alexa Fluor 555, Anti-mouse IgG Alexa Fluor 488 (Cell Signaling Technology Inc., MA, USA); Amersham ECL Western Blotting Detection Kit (GE Healthcare Life Sciences Inc., MA, USA); Alliance Q9 chemiluminescence imaging system (Uvitec Inc., UK); Tissue-Tek O.C.T. Compound (Sakura, Alphenaan den Rijn, Netherlands).

Neonatal foreskin tissues were obtained by surgical circumcision of healthy male neonates at the Pediatric Surgery clinic, King Chulalongkorn Memorial Hospital with parental informed consent and assent forms. Ethical approval for this study was granted by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University (IRB 120/63). We confirm that all methods and experiments were performed in accordance with relevant guidelines and regulations. Dermal fibroblasts were isolated as described previously17 and cultured in medium containing DMEM supplemented with 10% FBS and gentamicin (1mL/L). The cells were incubated in a 5% CO2 incubator at 37C, and the cells derived from the 2nd to 5th passage were used in experiments.

Dermal fibroblasts (5103 and 1104 cells/well) in 100 L of DMEM with 10% FBS were seeded into 96-well clear round bottom, ultra-low attachment plates. The medium was replaced with fresh medium every 3days18. Spheroids were imaged at days 3, 5 and 7 and diameters were measured by ImageJ.

Cell proliferation was analyzed by methylene blue staining. Dermal fibroblasts were seeded into a 96-well plate (3103 cells/well) with 1% FBS DMEM overnight. HNP1-3 (0.62510M) were added into the wells, and the cells were incubated for 24h. The supernatant was collected, and the cells were fixed with 20% (v/v) formaldehyde for 48h and stained with methylene blue for 30min. The cells were washed and eluted with 100 L of ice-cold HCl (0.1M) in absolute ethanol solution (1:1 ratio). The absorbance was measured at 650nm using microplate reader. Cytotoxicity was analyzed using LDH-Cytotoxicity Colorimetric Assay Kit II. Collected supernatants (2.5 L) were mixed with 25 L of LDH reaction mix for 30min. Stop solution (2.5 L) was added and the absorbance was measured at 450nm using microplate reader. Spheroids derived from dermal fibroblasts (5103 cells/well) were treated with HNP1-3 at 10M for 4days. All experiments were performed in triplicates.

Dermal fibroblasts were seeded into a 6-well plate (2.5105 cells/well) in DMEM containing 1% FBS overnight. The cells were treated with HNPs (2.5, 5 and 10M) for 24h. Total RNA was extracted and converted to cDNA with the following conditions: 25C for 5min, 46C for 20min and 95C for 1min. COL1A1 and Ki-67 gene expressions were determined by real-time PCR. ABL gene expression was used as internal control. Primers and probes are listed in Supplementary Table S1 online. Real-time PCR was performed for 40 cycles with the following program: 95C for 2min, 95C for 5s and 60C for 30s.

Dermal fibroblasts were seeded into a 6-well plate (2.5105 cells/well) in 1% FBS in DMEM overnight. HNPs (2.5, 5 and 10M) were added into the wells and the cells were incubated for 48h. Cells were lysed by 1X RIPA Lysis Buffer containing 1X Protease/Phosphatase Inhibitor Cocktail. Total protein concentration was measured by Pierce BCA Protein Assay Kit. Protein lysates (10g) were mixed with 2X SDS dye and heated at 100C for 5min. Proteins were loaded in 7.5% SDS-PAGE and gel electrophoresis was performed at 100V for 1.5h. Proteins were transferred to PVDF membrane with electrophoresis at 15V for 50min. Blotting membranes were blocked with 1X PBS with 0.1% Tween-20 (PBST) containing 5% skimmed milk, followed by incubation with primary antibodies; COL1A1 (1:2000) and -actin (1:4000), overnight at 4C. The membranes were washed with PBST, and mouse anti-rabbit IgG (HRP conjugate) secondary antibody (1:4000) was added. The membranes were incubated for 1h with shaking before washing. The membranes were soaked in chemiluminescent substrate (Amersham ECL Western Blotting Detection Kit) and chemiluminescence signals were directly scanned with Alliance Q9 chemiluminescence imaging system. The band intensity was quantified by densitometry using ImageJ.

Dermal fibroblasts were seeded into a Lab-Tek II Chamber Slide System (1.5104 cells/well) in 1% FBS in DMEM overnight. HNPs (2.5, 5 and 10M) were added into the cells and incubated for 24h. The cells were washed with PBS and fixed with 4% paraformaldehyde for 10min. The cells were treated with 0.2% Triton-100 in PBS for 2min and blocked with 1% BSA in PBS for 30min. Primary antibody: Ki-67 (1:1000), diluted in 1% BSA in PBS was added and the cells were incubated at 4C overnight. After washing, secondary antibody: anti-mouse IgG Alexa Fluor 488 (1:2000), diluted in 1% BSA in PBS was added and the cells were incubated for 1h. After washing, the sections were mounted and proteins were observed.

Spheroids derived from dermal fibroblasts (5103 cells/well) were treated with HNPs (10M) for 4days. The spheroids were collected and covered with Tissue-Tek O.C.T. Compound. Frozen spheroids were cryosectioned into 8m thick layers onto glass slides. The sections were washed with PBS, fixed with 4% paraformaldehyde for 10min and treated with 0.2% Triton-100 in PBS for 2min. The sections were blocked with 5% BSA in PBS for 1h and incubated with primary antibody: COL1A1 (1:400), diluted in 1% BSA in PBS at 4C overnight. After washing, the sections were incubated with secondary antibody: anti-rabbit IgG Alexa Fluor 555 (1:1000), diluted in 1% BSA in PBS for 1h. After washing, the sections were mounted and proteins were observed.

The statistical analyses were determined by paired t-test using GraphPad Prism 9.0.0 (GraphPad Software, Boston, MA, USA). A simple linear regression analyses was performed using STATA version 15.1 (StataCorp, College Station, TX USA). The regression coefficients, 95% confidence intervals (CI), and p-value were demonstrated. The results were expressed as the meanstandard deviation (SD) and differences with a p-value<0.05 were considered statistically significant.

Dermal fibroblasts were seeded into a 6-well plate (2.5105 cells/well) in DMEM containing 1% FBS overnight. The cells were treated with HNP1 (10M) for 24h. Total RNA was extracted and the quality of extracted RNA (RNA Integrity Number6.5) was evaluated using an Agilent 2100 Bioanalyzer. The RNA-seq experiment was conducted by Vishuo Biomedical, Thailand. Purified poly-A mRNA was fragmented, and pair-end RNA sequencing was performed on the Illumina HiSeq platform. The Gene Expression Omnibus (GEO) of raw reads in FASTQ files was GEO ID: GSE230670.

Quality of raw reads in FASTQ files was inspected with the FASTQC program (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The Trim Galore program (http://www.bioinformatics.babraham.ac.uk/projects/trim_galore/) was used to cut adaptors and sequence reads with a Phred score lower than 30. To estimate abundance of transcript, cleaned raw reads were analyzed with Salmon v1.9.019 by 2 steps; (1) indexing and (2) quantification. First, Salmon with default setting was used to build an index on human reference transcriptome (GRCh38) downloaded from Human Genome Resource at NCBI (downloaded; July 2022) (https://www.ncbi.nlm.nih.gov/projects/genome/guide/human/). Next, Salmon was used for quantification by mapping paired-end reads to the indexed reference sequence in mapping-based mode. Transcript abundances in estimated read counts were imported to R with tximeta v1.12.420 and aggregated to gene-level expression with gene model annotation (GRCh38) for further analysis. Principal component analysis (PCA) was performed on the pre-processed gene expression data, which were first log-transformed and normalized with respect to library sizes by the rlog function in DESeq221 package and standardized so that the expression level of each gene has a zero mean and a unit variance, to visualize the clustering structure of replicates. PCA plots were drawn in R using the ggplot2 package.

Differential gene expression was tested between HNP1 and control groups with DESeq2 v1.34.021 package. Gene expression was normalized with the median of ratios method from DESeq2. Since samples were derived from different donors, statistical design for DESeq2 was accounted for donor factor when fitted generalize linear model to data. Multiple hypothesis testing correction was performed using Benjamini-Hochberg's procedure. Differentially expressed genes (DEGs) were defined as genes with false discovery rates (FDR)<0.01. Boxplots were drawn in R using ggplot2.

Function of genes was analyzed with gene set enrichment analysis (GSEA) from WebGestalt (http://www.webgestalt.org/)22. The values of log fold changes were used to rank genes for the functional enrichment analysis using Gene Set Enrichment Analysis (GSEA) method. KEGG pathway and Gene Ontology databases (biological process, molecular function and cellular component) were used. Multiple hypothesis testing correction was performed using Benjamini-Hochbergs procedure with the FDR cutoff of 0.05 for enriched functions.

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Regulation of dermal fibroblasts by human neutrophil peptides ... - Nature.com

Fears mount that World Surf League has pushed equality too far … – BeachGrit

It isnt over yetthere could be consequences later

The name may not ring any bells if youve come into surfing late, but tour surfer Roy Powers, who was active in the early two thousands, sure knew how to steer a surfboard, winning at Haleiwa (beating Joel Parkinson) and Steamer Lane.

In 2007, ESPN ran a glittery profile on the kid.

He is quick to smile, just as quick to laugh; the sort of engaging, good-humored optimist given to saying such things as, All those pissed-off terrorists? They have to laugh too, dont they?

And Powers has reason to laugh. As a top professional surfer he has sponsorship deals that pay him well into six figures. He has a travel fund that covers his trips to surfing contests all over the world, including Australia, Tahiti, France and South America. He owns a home about a mile from here plus a house on the Big Island hes never seen. He recently fulfilled a lifelong dream by winning the Reef Hawaiian Pro competition, guaranteeing himself a spot on the World Championship Tour next season. And on this beautiful December day, he golfed in the morning, will surf a bit in the afternoon and has prime tickets for the next evenings Hawaii Warriors football game with his father. He is 26, tan, lean, muscled and has never had to worry about his weight.

If you really want to appreciate how large Powers lives, consider this story he tells. When he finally secured a date with a girl he had a crush on for years, he took her to a strip club in Honolulu, where he gave her 500 $1 bills and had her make it rain. Its not classy, he says, but it worked.

But while his career mightve ended up a little lacklustre, Powers was a close friend of Andy Irons and drifted off the tour after his pals death in 2010, what was happening behind the scenes sure wasnt dull.

In an extraordinarily candid interview with the The QuiverCasts Mike Steele, Powers, now forty-two, tells of a double life as a pro surfer and a drug dealer, working in a dark world where drug kingpins offered to kneecap his competitors and who wouldnt think twice, says Powers, about blowing your car up with you in it.

Thing is, says Powers, where theres excitement happening, ie at a surf contest, theres drugs and the way those things get there is by criminals and gangsters and organised crime. Its everywhere.

Powers is forced to talk in generalisations, naturally, like, whats he gonna do, name names, but the candour is wild.

The real fuckers that are collectng the big money, theyre mellow, normal people, mellow guys they dont commit petty crime, they dont get involve bed in bullshit they smile at you and shake your hand, but they dont have a problem with blowing your car up with you in it

I saw some things thatfuckI followed orders.

The last years on tour I wasnt really into it, especially the year after Andy died. Im really going to the dark side, but Im thriving in that I got a lot of respect. I was able to build connections to help people I knew who really wanted to be that worldfor people to get certain thingsa level of quantity or quality they could never get. I was in that position and had done business and spread blood for them.

I was doing some of the product. It fucks with your mind. Anybody who says you can control things, you cant brother. The shit grabs ahold of you. If youre around heavy negative things, youre going to start thinking heavy psychotic things.

Being locked in a cage and realising you have no choice of what youre doing, if you can eat, whats going to happen in the next ten seconds. That really hit me but it was also refreshing. I was out of that world. I would hit the restart button.

(In prison) everyones starving, everyones trying not to get stabbed, theres the gang politics, the predators every single moment of the day. Being a white guy in a Hawaiian prison system is fucked. Youre a minority but I knew how to operate. The gang I was operating with inside was top notch. We were like a military unit in there.

Fred Pattachia wrote me a letter. It hit me so hard. His passionate words from twenty-five years of friendship. He cared! I read it all the time.

Ive done some heavy heavy shit.

It isnt over yet. There could be consequences later.

Gets real good around the thirty-six minute mark.

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Fears mount that World Surf League has pushed equality too far ... - BeachGrit

Improving blood stem cell transplantation outcomes by treating donors – Fred Hutch News Service

Are you a good bone marrow donor and if not, can you become one? There are 55,000-60,000 blood stem cell transplantations also known as bone marrow transplants performed across the globe each year. A serious complication known as graft-versus-host disease (GVHD) is diagnosed for over half of these patients and occurs due to donor cells attacking healthy cells in the recipient. GVHD can be present in an acute or chronic form. While donor cells in GVHD are in attack mode, there may be ways to re-program them to be better resident cells in their new host. This idea comes from a body of literature that suggests statins, a common class of cholesterol-lowering drugs, can alter immune function. To evaluate this, a handful of studies have looked at either long-term or short-term statin treatment of donors and found differing results, but even so some findings from retrospective studies indicated that treatment of donors reduced the incidence of GVHD when recipients were also taking specific types of immunosuppressive drugs. Continuing investigation of this topic, Dr. Marco Mielcarek, a Professor in the Clinical Research Division at Fred Hutchinson Cancer Center and his team performed two prospective studies. Like the previous study on long-term statin treatment, they observed a reduction in GVHD incidence for cases in which donors received long-term statin treatment and recipients were taking the specific immunosuppressant cyclosporine (CSP), but not for those recipients who did not take CSP. These studies were published recently in Transplantation Cellular Therapy.

To prevent incidence and severity of GVHD, and thereby make allogeneic transplantation safer, transplant recipients typically receive prophylaxis consisting of several immunosuppressive medications, commented Dr. Mielcarek. Most of the time, these medications have to be taken for months (sometimes years). These drugs that suppress the immune system also make the person more susceptible to infection and other toxicities. Dr. Mielcarek continued, Therefore, using a medication that could be given to allogeneic stem cell donors for a limited time before they donate stem cell products for transplantation would be an innovative way of preventing GVHD without causing the toxicity of immunosuppressive drugs given to recipients. Pre-clinical studies support the use of statin treatment of donors to alter T cell function and reduce inflammatory effects, both of which would be beneficial to reducing the probability of developing GVHD in the recipient. Two large retrospective studies from the Mielcarek group suggested that donor statin use reduced the risk of severe acute GVHD in patients who were also taking CSP, added Dr. Mielcarek. Since these studies were performed as retrospective analyses, the researchers set out to perform prospective studies to investigate the outcome of short- or long-term statin treatment of donors on the occurrence of GVHD in two recipient groups, those taking CSP and those that were not.

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Improving blood stem cell transplantation outcomes by treating donors - Fred Hutch News Service

The salvage role of allogeneic hematopoietic stem-cell … – Nature.com

Baseline characteristics

A total of 52 adult patients with R/R DLBCL were identified and enrolled. The median age at diagnosis was 45years (range, 1763), with marginal male predominance (n=30, 57.7%). 36 patients (69.2%) were identified as having an advanced-stage disease (Ann Arbor stage IIIIV), whereas 15 (28.8%) suffered from B symptoms. Thirteen patients (25.0%) had BM involvement of DLBCL at the time of diagnosis, and 8 of 13 (61.5%) had complex karyotypes. All enrolled patients were classified as low (n=15, 28.8%), low-intermediate (n=13, 25.0%), high-intermediate (n=14, 26.9%), and high (n=10, 19.2%) risks based on international prognostic index (IPI) risk classification. Four patients had a double-hit mutation (7.7%), and according to Hans criteria, 32 and 13 patients were categorized as ABC type (61.5%) and GCB type (25.0%), respectively. The baseline characteristics at the time of diagnosis are summarized in Table 1.

Notably, most enrolled patients had previously undergone intensive treatments, and the median number of chemotherapy lines before allo-HSCT was 4 (range, 26). Sixteen patients (30.8%) had previously undergone auto-HSCT, and the median time from diagnosis and auto-HSCT to allo-HSCT was 27.1months (range, 6.2117.7months) and 18.5months (range, 6.544.8months), respectively. The disease status at the time of transplantation was CR (n=14, 26.9%), PR (n=16, 30.8%), and active disease (n=22, 42.3%). Donor types included matched sibling (n=18, 34.6%), haploidentical (n=18, 34.6%), matched unrelated (n=11, 21.2%), and unrelated donors with one allele mismatch (n=5, 9.6%). The conditioning regimen comprised MAC (n=2, 3.9%) and RIC (n=50, 96.1%). Half of the enrolled patients were ABO-type matched (n=26, 50.0%), 27 (51.9%) were in donor-to-recipient sex mismatch, and 44 (84.6%) were both donor and recipient cytomegalovirus (CMV) IgG seropositive. Table 2 presents the demographic information of the patients who underwent allo-HSCT.

Over a median follow-up period of 38.3months (range, 1.9112.0), the estimated 5-year OS and EFS were 38.4% (95% CI, 24.751.8) and 30.6% (95% CI, 18.843.3), respectively. The estimated 5-year CIR, NRM, and GRFS were 36.7% (95% CI, 23.649.8), 32.7% (95% CI, 20.345.6), and 15.1% (95% CI, 6.926.2), respectively. Figure1 shows the 1-year (100days outcomes in CIR and NRM) and 5-year survival outcomes. Compared to the active-disease group, the remission-achieved group showed a significantly superior rate of CR in the first 3months after allo-HSCT (76.7% vs. 36.4%, p=0.003) and at the last follow-up (50.0% vs. 13.6%, p=0.006) (Fig.2). Moreover, except for NRM (26.7% vs. 40.9%, p=0.217), the clinical outcomes of OS (54.1% vs. 15.6%, p=0.001), EFS (46.4% vs. 9.1%, p<0.001), and GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with lower CIR (26.9% vs. 50.0%, p=0.047). In detail (Fig.3), among patients in the remission-achieved group before allo-HSCT (n=30), 23 achieved CR, one achieved PR, four experienced disease relapse after allo-HSCT and died due to disease progression, and three died after engraftment (two from bacterial septic shock and one from veno-occlusive disease [VOD]) without relapse. In contrast, among patients in the active-disease group before allo-HSCT (n=22), eight achieved CR. However, only two remained in CR, four experienced disease relapse, and two died due to septic shock during disease remission. All eight of the remaining patients who achieved PR eventually relapsed, and six died after engraftment either due to allo-HSCT-related complications (one with grade IV hemorrhagic cystitis combined with renal failure, one with VOD, and two with grade IV acute hepatic GVHD complicated with liver failure) or infection (two with CMV pneumonia).

Survival outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma after undergoing allogeneic hematopoietic stem-cell transplantation. The estimated 1- and 5-year (A) OS is 45.0% (95% CI, 30.758.3) and 38.4% (95% CI, 24.751.8). The estimated 1- and 5-year (B) EFS is 32.7% (95% CI, 20.545.4%) and 30.6% (95% CI, 18.843.3). The CIR and NRM at day 100 after allo-HSCT is (C) 15.4% (95% CI, 7.126.5) and (D) 17.3% (95% CI, 8.528.8). Furthermore, the estimated 5-year CIR and NRM are 36.7% (95% CI, 23.649.8) and 32.7% (95% CI, 20.345.6), respectively. The estimated 1- and 5-year (E) GRFS is 17.3% (95% CI, 8.528.6) and 15.1% (95% CI, 7.026.2). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

Response rate and clinical course of patients with diffuse relapsed/refractory large B-cell lymphoma after undergoing allogenic hematopoietic stem-cell transplantation. (A) Remission-achieved group: Among 30 patients in the remission-achieved group, the overall response rate (23 CR and 1 PR) was 80.0% (n=24) at 3months after allo-HSCT. At the last follow-up, 15 patients remained CR (including 1 PR patient who achieved CR after donor leukocyte infusion), but three died after engraftment without relapse, and six experienced DLBCL relapse. (B) Active-disease group: Among 22 active-disease group patients, the overall response rate (8 CR and 8 PR) was 72.7% (n=16) at 3months after allo-HSCT. However, at the last follow-up, only two patients remained CR, two died after engraftment without relapse, and 12 (4 CR and 6 PR) experienced DLBCL relapse. CMV, cytomegalovirus; CR, complete remission; GVHD, graft-versus-host disease; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; PD, progression of disease; PR, partial remission.

Comparison of survival outcomes between the remission-achieved and active-disease groups in patients with diffuse large B-cell lymphoma who underwent allogeneic hematopoietic stem-cell transplantation. The clinical outcomes of (A) OS (54.1% vs. 15.6%, p=0.001), (B) EFS (46.4% vs. 9.1%, p<0.001), and (E) GRFS (22.9% vs. 4.6%, p=0.002) were significantly superior in the remission-achieved group with (C) lower CIR (26.9% vs. 50.0%, p=0.047), except for (D) NRM (26.7% vs. 40.9%, p=0.217). CI, confidence interval; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease-free, relapse-free survival; HSCT, hematopoietic stem-cell transplantation; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

The overall cumulative incidence of grade 3 to 4 acute GVHD and moderate-to-severe chronic GVHD that required steroid pulse therapy was 17.3% (95% CI, 8.528.8%) and 29.1% (95% CI, 17.242.0%), respectively. The active-disease group had a significantly higher incidence of grade 34 acute GVHD than the remission-achieved group before allo-HSCT (6.7% vs. 31.8%, p=0.023). However, no significant differences in moderate-to-severe chronic GVHD incidence (37.1% vs. 18.2%, p=0.172) were observed between the two groups. The allo-HSCT-related complication incidence, response rate, and survival outcomes in the remission-achieved and active-disease groups before allo-HSCT are presented in Table 3.

The results of the univariate analysis for OS, EFS, CIR, NRM, and GFRS are presented in Supplementary Tables 1 and 2. In the multivariate analysis, a shorter interval from diagnosis to allo-HSCT (median of<27.1months), which reflects relatively rapid disease progression, showed significantly poor OS (hazard ratio [HR], 3.92; 95% CI, 1.838.43; p<0.001) and EFS (HR, 2.65; 95% CI, 1.285.46; p=0.008). Complex karyotypes in BM involving DLBCL were also associated with poor OS (HR, 1.42; 95% CI, 1.061.90; p=0.018) and NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). Active disease before allo-HSCT was associated with significantly lower EFS (HR. 2.50; 95% CI, 1.215.17; p=0.014), GFRS (HR, 2.54; 95% CI, 1.374.72; p=0.003), and higher CIR (HR, 3.03; 95% CI, 1.148.02; p=0.026). The MAC regimen for allo-HSCT was associated with significantly higher CIR (HR, 11.3; 95% CI, 3.3338.1; p<0.001), and patients with previous autologous stem-cell transplantation (ASCT) had significantly better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043). The results of the multivariate analysis are presented in Fig.4.

Multivariable analysis of survival outcomes related to allogeneic hematopoietic stem-cell transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma. (A) The multivariable analysis for each survival outcome shows that a shorter interval of the median of<27.1months from diagnosis to allo-HSCT (HR, 3.92; 95% CI, 1.838.43; p<0.001) and complex karyotype presenting bone marrow (HR, 1.42; 95% CI, 1.061.90; p=0.018) are significantly related to poor OS. In the case of EFS, a shorter interval compared to the median of<27.1months from diagnosis to allo-HSCT (HR, 2.65; 95% CI, 1.285.46; p=0.008) and active disease before allo-HSCT (HR, 2.50; 95% CI, 1.215.17; p=0.014) are significantly related to poor EFS. Previous ASCT are significantly related to better GRFS (HR, 0.50; 95% CI, 0.260.98; p=0.043), but active disease before allo-HSCT are significantly related to poor GRFS (HR, 2.54; 95% CI, 1.374.72; p=0.003). (B) Active disease before allo-HSCT (HR, 3.03; 95% CI, 1.148.02; p=0.026) is also significantly related to higher CIR with MAC conditioning (HR, 11.3; 95% CI, 3.3338.1; p<0.01). Complex karyotype presenting bone marrow is also related to higher NRM (HR, 1.41; 95% CI, 1.021.94; p=0.040). CI, confidence interval; ASCT, autologous stem-cell transplantation; CIR, cumulative incidence of relapse; EFS, event-free survival; GRFS, graft-versus-host disease free, relapse-free survival; HR, hazard ratio; HSCT, hematopoietic stem-cell transplantation; MAC, myeloablative conditioning; NRM, non-relapsed mortality; OS, overall survival; R/R DLBCL, relapsed/refractory diffuse large B-cell lymphoma.

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