Hematological Oncology最新文献

Involvement of female genital track (FGT) by diffuse large B cell lymphoma (DLBCL) represents an extremely rare diagnosis. Especially data regarding early-stage disease (i.e., IE, IIE) is very limited. Importantly, previous studies showed controversial results about the risk of central nervous system (CNS) relapse in this entity. Herein, we describe one of the largest reported real-world series of patients with early-stage FGT DLBCL aiming to investigate the clinicopathological characteristics, response to therapy and survival outcomes in the era of immunochemotherapy. We analyzed 21 consecutive patients with biopsy proven DLBCL from uterus or ovary classified as stage IE or IIE out of 1905 newly diagnosed DLBCL patients (1.1%). Uterine and ovarian localization was observed in 14 and seven patients, respectively. Median age was 66 years (range 33–96); 9/21 (43%) were <55 years. Regarding Cell of Origin DLBCL subtype, Germinal Center B-cell subtype was found in seven patients, non-GCB in 10 and non-classified in 4 patients. Median follow-up was 57 months and 5-year overall survival, lymphoma specific survival and Freedom from Progression were 78%, 89% and 90%, respectively. There was no correlation of patients' characteristics with survival parameters. Interestingly, none of the patients experienced CNS relapse. Our results indicate that localized FGT DLBCL exhibits a good prognosis and may not increase the risk for secondary CNS involvement.

Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD-L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B-cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline. The overall response rate to ICIs was 30.5%, with no association between patients clinical characteristics and response/survival outcomes. Regarding GM, responder patients showed a peculiar significant enrichment of Lachnospira, while non-responder ones showed higher presence of Enterobacteriaceae (at baseline and maintained till EoT). Recognizing patient-related factors that may influence response to ICIs is becoming critical to optimize the treatment pathway of heavily pretreated, young patients with a potentially long-life expectancy. These preliminary results indicate potential early GM signatures of ICIs response in lymphoma, which could pave the way for future research to improve patients prognosis with new adjuvant strategies.

To retrospectively analyze whether the second revision of the international staging system (R2-ISS) influenced prognosis at treatment initiation in patients with multiple myeloma (MM) receiving anti-CD38 antibody-based triplet treatments. High-risk chromosomal abnormalities were examined from diagnosis to treatment initiation and considered positive if detected once. R2-ISS was recalculated at the initiation of treatment and defined as “dynamic R2-ISS." Data from 150 patients who underwent the defined treatments were analyzed. The median progression-free survival (PFS) was 19.5 months, and the median overall survival (OS) was 36.5 months. Dynamic R2-ISS significantly stratified prognoses for both PFS and OS. The median PFS for patients with dynamic R2-ISS IV was 3.3 months, and the median OS was 11.7 months, indicating extremely poor outcomes. Although the Revised International Staging System (R-ISS) calculated at the initiation of treatment significantly stratified treatment outcomes, the patients classified as R-ISS could be further stratified by R2-ISS to provide better prognostic information. Dynamic R2-ISS showed potential as a prognostic tool in patients with MM who are treated with anti-CD38 antibody-based triplet therapies.

Previous research has demonstrated that the combination of Venetoclax (Ven) and intensive chemotherapy (IC) enhances the complete response (CR) and minimal residual disease (MRD) negative rate in patients with de novo Acute Myeloid Leukemia (AML).^1-5 Our previous study showed that Ven combined with DA (2 + 6) is a highly effective and safe induction therapy for AML patients.¹ The objective of this data update is to further substantiate the efficacy and safety of this induction regimen.

Until 30 Nov 2023, 85 patients were enrolled in this study. Baseline characteristics of 85 patients are in Table S1. According to the ELN 2022 risk classification, 37 (43.5%), 13 (15.3%), and 35 (41.2%) patients belonged to the favorable, intermediate, and adverse groups, respectively.

After one cycle induction therapy, the overall response rate (ORR, CR + CRi + PR) was 94.1% (80/85) with a composite complete response rate (cCR, CR + CRi) of 91.8% (78/85) and 85.7% (60/70) of the patients reached cCR with MRD (−) by flow cytometry. The cCR rate was 97.3% (36/37) in patients with ELN (2022) favorable risk, 84.6% (11/13) in patients with intermediate risk, and 88.6% (31/35) in patients with adverse risk (Table 1). The adverse effects and recovery time of blood cells consistent with our previous reports. Tumor lysis syndrome was only observed in one patient, and one patient died during induction therapy.

Until 30 Jan 2024, with a median follow-up of 12 (0.5–24) months, eleven (11/84, 13.1%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The estimated 12-month overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) rates were 82.2%, 81.9%, 82.7%, respectively (Figure S1). According to the 2022 ELN prognostic risk classification, the estimated 12-month OS, EFS, and DFS rates were 93.5% (95% CI: 88.3%–98.6%), 93.3% (95% CI: 88.1%–98.5%), and 93.3% (95% CI: 84.3%–100%), respectively, in favorable risk group; 91.7% (95% CI: 86.6%–96.8%), 90.0% (95% CI: 84.7%–95.3%), 90.9% (95% CI: 73.8%–100%), respectively, for intermediate-risk patients; and 64.6% (95% CI: 44.4%–84.8%), 62.9% (95% CI: 41.9%–83.9%), and 64.9% (95% CI: 43.7%–86.1%), respectively for adverse-risk patients (Figure 1).

Our previous study showed that Ven combined with DA (2 + 6) is a highly effective and safe induction therapy. To further corroborate our previous results, we extended the study to continue enrolled patients and continue follow-up of earlier patients.

The updated results are shown that the ORR after one cycle of induction was 94.1% (80/85) with a cCR rate of 91.8% (78/85) and MRD (−) rate 85.7%. The rates of cCR, MRD negativity, and recovery time for neutrophils and PLT counts were consistent with our previous report. The results further substantiate the efficacy and safety of our induction regimen. In comparison to previous reports,^{2, 4, 5}

The biological role of Ten-11 translocation 2 (TET2) and the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in the development of extra-nodal natural killer/T-cell lymphoma (ENKTL) remains unclear. The level of 5mC and 5hmC was detected in 112 cases of ENKTL tissue specimens by immunohistochemical (IHC) staining. Subsequently, TET2 knockdown and the overexpression cell models were constructed in ENKTL cell lines. Biochemical analyses were used to assess proliferation, apoptosis, cell cycle and monoclonal formation in cells treated or untreated with L-Ascorbic acid sodium salt (LAASS). Dot-Blots were used to detect levels of genome 5mC and 5hmC. Additionally, the ILLUMINA 850k methylation chip was used to analyze the changes of TET2 regulatory genes. RNA-Seq was used to profile differentially expressed genes regulated by TET2. The global level of 5hmC was significantly decreased, while 5mC was highly expressed in ENKTL tissue. TET2 protein expression was negatively correlated with the ratio of 5mC/5hmC (p < 0.0001). The 5mC/5hmC status were related to the site of disease, clinical stage, PINK score and Ki-67 index, as well as the 5-year OS. TET2 knockdown prolonged the DNA synthesis period, increased the cloning ability of tumor cells, increased the level of 5mC and decreased the level of 5hmC in ENKTL cells. While overexpression of TET2 presented the opposite effect. Furthermore, treatment of ENKTL cells with LAASS significantly induced ENKTL cell apoptosis. These results suggest that TET2 plays an important role in ENKTL development via regulation of 5mC and 5hmC and may serve as a novel therapeutic target for ENKTL.

Alderuccio, J.P., Saul, E.E., Stanchina, Polar, M.K, M., Sassi, R.H., Zhao, W., Moskowitz, C.H., Reis, I., Kuker, R.A., Lossos, I.S. (2023), Staging FDG-avidity in extranodal marginal zone lymphoma (EMZL) by disease location. Hematological Oncology, 41: 103–104. https://doi.org/10.1002/hon.3163_64

In the author byline, the middle initials of the authors are missing, and the sequence is incorrect.

The incorrect author byline is:

J. P. Alderuccio, E. Edelman Saul, M. Stanchina, R. Hennemann Sassi, W. Zhao, C. Moskowitz, I. Reis, R. Kuker, I. Lossos, M. Polar

The correct author byline should be:

J.P. Alderuccio, E. Edelman Saul, M.D. Stanchina, M.K. Polar, R. Henneman Sassi, W. Zhao, C.H. Moskowitz, I. Reis, R.A. Kuker, I.S. Lossos

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3 months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6 months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6 months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p = 0.006), and achievement of ≥VGPR (OR 21.7 p < 0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p = 0.09). With a median follow-up of 36.4 months, the median overall survival (OS) was 11 months. On multivariable analysis, achievement of renal response (hazard ratio [HR] 0.3, p < 0.0001) and newly diagnosed disease (NDMM; HR 0.43, p = 0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p = 0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise.