To retrospectively investigate the short-term efficacy and safety of the triple-drug combination regimen of venetoclax + azacitidine + homoharringtonine (VAH regimen) in patients with acute myeloid leukemia (AML).

We compared outcomes of patients ≥ 70 years old undergoing allogeneic stem cell transplantation (alloSCT) with graft-vs-host disease (GvHD) prophylaxis regimens either including post-transplant cyclophosphamide (PTCy) or without cyclophosphamide (non-Cy). The primary endpoint was GvHD-free, relapse-free survival (GRFS) at one and five years; secondary endpoints included clinically significant acute (grade III-IV) and chronic (extensive) GvHD, relapse, overall survival (OS), and non-relapse mortality (NRM). Among 61 patients, 41 received PTCy and 20 received non-Cy prophylaxis. Unrelated donors accounted for 80 % of allografts; all non-Cy patients had 10/10 HLA matches, while PTCy patients had 64 % matched, 29 % haploidentical, and 7 % mismatched unrelated donors. Acute GvHD occurred in 5 % of PTCy vs 15 % of non-Cy patients (p = ns). One-year chronic GvHD incidence was lower with PTCy (12 % vs 30 %, p = 0.03). One-year GRFS was similar (34 % PTCy, 35 % non-Cy; p = ns). At five years, OS was 20 % vs 30 % and GRFS 21 % vs 15 % for PTCy and non-Cy, respectively (p = ns). We observed similar outcomes among patients receiving GvHD prophylaxis with PTCy compared to non-Cy. Importantly, non-Cy patients had HLA-matched donors, whereas mismatched donors were possible for the PTCy group. In this way, PTCy seems to have equalized outcomes for fully matched and mismatched alloSCT by yielding similar one and five-year GRFS. We also found no significant difference in relapse rate, NRM, OS, and five-year GRFS between patients aged 70-74 and ages 75 + , showing that numerical age should not be a contraindication to alloSCT.

The current standard of care for acute myeloid leukemia (AML) patients undergoing intensive induction chemotherapy includes an interim bone marrow biopsy around day 14 (D14BM), and reinduction for patients with more than 5 % residual blasts on D14BM (Positive D14BM). However, this approach has become increasingly controversial. This systematic review and meta-analysis assess the sensitivity, specificity, and predictive value of D14BM in patients treated with one cycle of induction chemotherapy and evaluate the efficacy of reinduction versus observation in patients with Positive D14BM.

Our previous findings indicate Semaphorin 4D (Sema4D) as a potential pediatric leukemia biomarker, promoting leukemogenesis via PI3K/AKT and ERK pathways, but its upstream regulatory mechanisms remain unclear. This study was conducted to explore the potential regulatory relationship between Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) and Sema4D in acute myeloid leukemia (AML).

Polycythemia vera (PV) is characterized by overproduction of erythrocytes, leukocytes, and platelets. Rusfertide is a hepcidin mimetic polypeptide that binds to ferroportin and decreases iron delivery to bone marrow, reducing the production of red blood cells. The primary objective of this study was to evaluate the efficacy and safety of rusfertide in patients with PV and elevated (>48 %) baseline hematocrit. Patients were treated with 40 mg subcutaneous rusfertide twice weekly until their hematocrit reached < 45 %; once achieved, patients received weekly rusfertide dosing. Of the 20 patients enrolled, 15 (75 %) completed 24 weeks of treatment, 13 (65 %) completed 52 weeks, and 7 discontinued rusfertide therapy. Mean baseline hematocrit was 51.6 %. By Week 8, 17 (85 %) patients achieved hematocrit < 45 %, and 19 (95 %) achieved ≥ 5 % absolute reduction from baseline. Median time to first hematocrit < 45 % was 4.9 weeks. Mean hematocrit was < 45 % at Week 4 and subsequently remained < 45 % throughout the study. No patients received phlebotomy during rusfertide treatment. Rusfertide led to a significant reduction in erythrocyte count (5.98 ×10/L to 4.79 ×10/L; nominal p-value 0.0036) and an improvement in iron deficiency markers (eg, ferritin and mean corpuscular volume) relative to baseline. Seventeen patients (85 %) experienced treatment-emergent adverse events, most of which were Grade 1/2. In this open-label phase 2 study, rusfertide resulted in a rapid and sustained improvement in hematocrit and was generally well tolerated. Rapid and sustained control of hematocrit reduces the need for therapeutic phlebotomy and may help reduce thrombotic and cardiovascular events over the long term in patients with PV.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative outcomes for chronic myelomonocytic leukemia (CMML). We conducted a retrospective study to clarify the protective impact of acute and chronic graft-versus-host disease (aGVHD and cGVHD) on relapse by transplant procedures in 314 CMML patients. Interaction effects of conditioning intensity were observed with aGVHD (P=0.181) and cGVHD (P=0.256) for the cumulative incidence of relapse (CIR), whereas interaction effects of donor type were not detected with GVHD. In patients with the myeloablative conditioning regimens, the multivariate analysis showed that the development of aGVHD was not associated with overall survival (OS). The development of limited cGVHD correlated with better OS (HR [95 % CI], 0.34 [0.14-0.81]; P = 0.015); and that of extensive cGVHD correlated with better OS (HR, 0.44 [0.21-0.91]; P = 0.026) and lower CIR (HR, 0.28 [0.08-0.94]; P = 0.040). In patients with the reduced-intensity conditioning regimens, the development of grade I-II aGVHD correlated with better OS (HR, 0.39 [0.20-0.76]; P = 0.005) and lower CIR (HR, 0.30 [0.13-0.70]; P = 0.006). The development of extensive cGVHD correlated with better OS (HR, 0.44 [0.20-0.96]; P = 0.039). The present results suggest that the type and severity of GVHD mediating graft-versus-leukemia effects against relapse were influenced by conditioning intensity in CMML patients.

With the evolving treatment landscape and growing therapeutic options, it is essential to understand the treatments currently used in real-world clinical practice and the associated outcomes among patients with DLBCL to identify potential unmet treatment needs.

There is growing evidence that exosomes produced by bone marrow stromal cells (BMSCs) are associated with the progression of several cancers, including acute myeloid leukemia (AML), but intrinsic molecular mechanisms remain elusive. Here, we applied previous microarray analysis (GSE133276 and GSE209871) to identify differentially expressed exosomal miRNAs in BMSCs of AML patients, and candidate miR-140-3p, miR-142-5p and miR-142-3p were selected. This study aimed to investigate whether BMSCs affects AML progression are mediated by the candidates, and to explore regulatory mechanisms. The levels of the candidates were examined in bone marrow and BMSCs from AML patients, and exosomes from BMSCs of normal subjects and AML cells by qRT-PCR. Cell proliferation and apoptosis of AML cells co-cultured with BMSCs were detected through CCK-8, colony formation, flow cytometry, and Caspase-3 activity assays with manipulation of the candidate miRNAs expression. RNA pull-down and luciferase reporter assays to identify the downstream target mRNAs of the miRNAs. We confirmed that miR-140-3p, miR-142-5p and miR-142-3p levels were downregulated in bone marrow and BMSCs of AML patients, and were significantly enriched in exosomes of BMSCs but not AML cells. BMSCs co-cultured with AML cells could transfer these miRNAs into AML cells, and suppressed the proliferative potential and promoted the apoptotic behavior of AML cells. Furthermore, miR-140-3p agomir in BMSCs exacerbated the effects of the co-culture system on the AML cell proliferation and apoptosis, which were attenuated by miR-140-3p antagomir. In contrast, co-culture data showed that miR-142-5p and miR-142-3p had no significant effect on cell proliferation and apoptosis. Moreover, SUZ12 polycomb repressive complex 2 subunit (SUZ12) was directly targeted by miR-140-3p, overexpression or inhibition of SUZ12 in AML cells partially counteracted miR-140-3p agomir or antagomir-mediated cellular effects, respectively. Our study suggested that the BMSCs-derived exosomal miR-140-3p, rather than miR-142-5p and miR-142-3p, has a regulatory effect on the growth and apoptosis of AML cells by targeting SUZ12.

Complement C3, a critical component of the complement system, has been implicated in cancer risk across various malignancies. However, its role in myelodysplastic syndromes (MDS) remains inadequately explored. This study investigates the impact of serum complement C3 levels on survival outcomes in patients with MDS.

Infectious complications remain the major cause of treatment-related morbidity and mortality in pediatric patients with acute lymphoblastic leukemia (ALL). This study retrospectively compared the patterns of infection in children treated with either the modified St. Jude Total XV protocol (n = 181) or the ALL-IC BFM 2009 protocol (n = 61) at a single center. Although the overall number of infection episodes was similar between the two groups, their distributions across treatment phases differed markedly. The ALL-IC BFM 2009 protocol was associated with a significantly greater incidence of infections during the induction phase, particularly in high-risk patients, who often presented with skin and gastrointestinal tract infections. In contrast, modified St. Jude Total XV protocol presented a greater infection risk during the re-induction phase. Gram-positive bacteria, especially Staphylococcus epidermidis, were the most frequently isolated pathogens in both cohorts, although the BFM group exhibited a higher proportion of gram-negative infections. The rates of documented viral infections in BFM cohort and modified St. Jude Total XV cohort were 21.4 % vs 9.2 %, respectively. Invasive fungal infection rate was found as 6.7 % in the modified St. Jude group and 4.0 % in the BFM group is in line with the literature. Multivariate analysis confirmed that severe neutropenia and the presence of a central venous catheter were strong independent predictors of infection frequency. These findings underscore protocol-specific differences in infectious risk profiles and emphasize the importance of tailored supportive care strategies in the management of pediatric ALL.

Richter transformation (RT) represents the development of an aggressive lymphoma in chronic lymphocytic leukemia (CLL). Patients with RT and relapsed CLL have poor outcomes. Yet, the molecular differences between the two entities have not been fully explored. In this pilot study, we conducted RNA-seq and targeted panel sequencing of nodal tissues from 12 patients, including seven with RT and five with CLL. Analysis of RNA-seq data revealed two major clusters, with five RT in cluster C1 and the remaining two RT and all five CLL in C2. Within C2, one of the CLL ultimately developed RT; it showed more similarity to the two RT than to the other CLL in expression profile, suggesting the presence of expression signature for RT prior to the clinical diagnosis. In addition, differentially expressed genes, the majority of which showed higher expression in C1 relative to C2, were enriched in pathways known to be important for CLL pathogenesis or transformation. Deconvolution of the bulk RNA-seq data revealed major differences in cellular composition between the two clusters, notably tumor B cells, macrophages M1, and CD8 + T cells. Furthermore, by targeted sequencing, we identified 51 genes that carried recurrent copy number alterations (CNAs) preferentially occurring in either cluster. Over 80 % of these CNAs occurred in C2, mainly gains of 17q12q25 in CLL. Patients in C1 had shorter overall survival (median 11 months) compared to those in C2 (median 36 months). Together, our findings highlight noticeable differences in transcriptomic and genomic alterations between CLL versus RT.

Achieving complete response/remission (CR) by International Workshop on Chronic Lymphocytic Leukemia 2018 criteria indicates complete remission of leukemia in all disease compartments. We evaluated CR rate as a surrogate endpoint for progression-free survival (PFS) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) using data from randomized controlled trials (RCT). A systematic literature review was conducted to identify RCTs with ≥ 2 treatment arms, parallel group design, and reporting CR rate and PFS in patients with R/R CLL/SLL. Association between treatment effects on CR rate and corresponding PFS changes contrasting treatment and control arms was estimated using a weighted linear model, Daniels and Hughes model, and Riley bivariate random-effects meta-analysis. Association between absolute CR rate and PFS within individual treatment arms was estimated using nonparametric (Cox) and parametric (exponential, Weibull, Gompertz) proportional hazards models. Twenty RCTs were identified including 5765 patients with R/R CLL/SLL investigating various treatments (Bruton tyrosine kinase inhibitors, a B-cell lymphoma 2 inhibitor, phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cell therapy, anti-CD20 monoclonal antibody, chemotherapy). Across RCTs, higher odds of CR resulted in statistically significant lower hazards of disease progression/death, where each 10 % increase in CR rate was associated with a 26 % (95 % confidence interval, 22 %30 %) reduction in risk of progression/death. Cross-validation analyses demonstrated that treatment effects on CR rate reasonably predicted PFS benefits. Results were broadly consistent across different models. This study supports CR rate as an essential treatment goal and a valid surrogate endpoint in R/R CLL/SLL.

5-Azacitidine (5-Aza) is a hypomethylating agent with demonstrated therapeutic efficacy for myeloid leukemia. The aim of this study was to identify the genes that mediate the cell killing effect of 5-Aza against leukemia cells through their expression changes and DNA demethylation. RNA sequencing revealed 54 genes with increased transcription levels in both SKM-1 and KG-1a myeloid leukemia cell lines treated with 5-Aza. Long read sequencing revealed 79 genes in which intron 1 exhibited significant DNA demethylation after 5-Aza treatment. Forty-three genes showed both increased gene expression and DNA demethylation in intron 1 in cells treated with 5-Aza. Enrichment signaling pathway analysis demonstrated that genes were associated with "amino acid metabolism," "neutrophil degranulation," and "DNA damage response". We evaluated the prognostic impacts of the 43 genes in acute myeloid leukemia patients using TCGA database. The results revealed that two genes (HDC and MICALL2) with increased expression in leukemia cells after 5-Aza treatment were associated with better overall survival, while six genes (BTG2, CD52, PECAM1, PIK3IP1, PTGS2, and TREML2) correlated with worse overall survival. This study revealed that the epigenetic regulation by DNA demethylation in intron 1 has an important role of 5-Aza treatment in myeloid leukemia cells, and suggests novel targets for the development of combination therapy with 5-Aza.

In Australia, the number of people living with multiple myeloma (MM) is projected to increase. We examined the health system costs and autologous stem cell transplant (ASCT) receipt among participants with MM diagnosed between 2006 and 2019 from the Australian 45 and Up Study cohort (267,357 participants).

Neutropenic enterocolitis (NE) is an uncommon but serious complication in patients with acute myeloid leukemia (AML), often arising during periods of myelosuppression. Although recognized clinically, its broader impact on hospitalization outcomes and healthcare utilization in AML is poorly defined. To evaluate the association between NE and key inpatient outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges among patients with AML, this retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) from 2018 to 2022. Multivariable models were fitted using survey-weighted logistic regression for mortality and Poisson regression with a log link for LOS and charges, adjusting for demographic and clinical covariates to calculate adjusted odds ratios (aORs) and adjusted incidence rate ratios (aIRRs), with corresponding 95 % confidence intervals (CIs). Among an estimated 344,545 AML hospitalizations, 3865 involved NE, which were associated with significantly longer hospitalizations and higher costs. In adjusted models, NE increased LOS by nearly 50 % (aIRR: 1.47, 95 % CI: 1.41-1.54) and total charges by over 40 % (aIRR: 1.44, 95 % CI: 1.35-1.53), with both associations being highly significant (p < 0.0001). In contrast, NE was not independently associated with in-hospital mortality (aOR: 0.89, 95 % CI: 0.75-1.06; p = 0.20). This study's findings indicate that, though NE was not a predictor of mortality, it is a strong driver of healthcare utilization in patients hospitalized with AML. These findings underscore NE's importance as a complication with major clinical and economic implications, highlighting the need for strategies to improve recognition and management in this vulnerable population.