bims-hemali 2025-02-02 papers

bims-hemali

Biomed News

on Hematologic malignancies

Issue of 2025–02–02
eight papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό

Real World Evidence From 2 Decades of First-Line TKI Therapy in Chronic Myeloid Leukemia (CML): Insights From ACHO's RENEHOC Registry.
Venetoclax in combination with chidamide and azacitidine for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia with the MLL-AF4 gene: a case report and literature review.
Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma-A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone.
Blastic plasmacytoid dendritic cell neoplasm: a Swiss case series of a very rare disease and a structured review of the literature.
Six-month Rituximab-Lenalidomide regimen in advanced untreated Follicular Lymphoma: SAKK 35/10 Trial 10-year Update.
Tyrosine Kinase Inhibitor Therapy Enhances Stem Cells Profile and May Contribute to Survival of Chronic Myeloid Leukemiastem Cells.
Successful treatment of a chronic myeloid leukemia patient with extreme thrombocytosis by a combination of imatinib and interferon‑α: A case report.
Primary Renal Lymphoma: A Single-Center Study of 14 Cases.

Clin Lymphoma Myeloma Leuk. 2024 Dec 28. pii: S2152-2650(24)02464-9. [Epub ahead of print]

Real World Evidence From 2 Decades of First-Line TKI Therapy in Chronic Myeloid Leukemia (CML): Insights From ACHO's RENEHOC Registry.

Virginia Abello Polo, Claudia Sossa, Carla Boquimpani, Luis Antonio Salazar, Isabel Munevar, Rigoberto Gómez, Diana Marcela Cuervo, Carlos Varón Jaimes, Jheremy Reyes, Henry Idrobo, Paola Omaña, Jorge Daza, Julian Eduardo Pedraza Morales, Claudia Agudelo López, Guillermo E Quintero-Vega, Mario Correa Correa, Juan Manuel Herrera, William Armando Mantilla, Juan Carlos Serrano, Carmen Rosales, Kenny Mauricio Gálvez Cárdenas, Carlos Bermúdez, Domingo Saavedra Ramírez, Mauricio Alzate, José Fernando Lobatón Ramírez.

   BACKGROUND: Chronic myeloid leukemia (CML) treatment has significantly evolved with the introduction of tyrosine kinase inhibitors. However, access to these treatments and outcomes vary globally. This study examines 2 decades of CML management in Colombia using the RENEHOC registry, focusing on TKI efficacy, safety, and healthcare system challenges.
METHODS: We performed a descriptive analysis of the sociodemographic and clinical characteristics of 994 CML patients from the RENEHOC cohort in Colombia, who were treated over the past 20 years. Trends in first-line TKI use were assessed, and Kaplan-Meier survival curves were used to estimate EFS and OS. The log-rank test was used to compare survival curves between different first-line TKIs.
RESULTS: The analysis shows trends in the use of first-line TKIs over a 20-year period in Colombia, where, as in other countries, the use of second-generation TKIs in the first-line setting is gradually increasing. Despite the difficulties of the Colombian healthcare system, the results in terms of OS are excellent regardless of the first-line TKI; however, patients treated with imatinib switched lines significantly more often than those treated with second-generation TKIs (imatinib 58.7%, nilotinib 19.5%, dasatinib 29.3%). The median duration of treatment was significantly shorter with imatinib compared to dasatinib and nilotinib (4.08, 12.75 and not reached, respectively). Intolerance was the most common reason for switching in this cohort of patients. The median observation time for OS was 64.89 months (SD 60.15), with survival rates of 99.4% at 1 year, 97.7% at 3 years and 96.6% at 5 years.
CONCLUSIONS: The results of this analysis show excellent results in terms of OS for patients with CML treated in Colombia over the last 20 years, despite the difficulties inherent in the health system. Patients treated with first-line imatinib had more frequent line changes. In general, intolerance was the most common reason for switching lines. Despite its retrospective nature, this study allows us to outline how treatment patterns in the country have changed over time. Continued efforts to include more centers and patients in prospective studies are essential to better understand the long-term effects of treatment and to improve adherence to guideline recommendations in clinical practice.

Keywords:  Dasatinib; Imatinib; Nilotinib; RENEHOC registry; Tyrosine kinase inhibitors

DOI:  https://doi.org/10.1016/j.clml.2024.12.015
Front Immunol. 2024 ;15 1475974

Venetoclax in combination with chidamide and azacitidine for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia with the MLL-AF4 gene: a case report and literature review.

Xuelian Jin, Zhigang Liu, Yu Wu, Jie Ji.

  B-cell acute lymphoblastic leukemia (B-ALL) with the MLL-AF4 fusion gene has a poor prognosis, and the mortality rate exceeds 90%, particularly in cases of extramedullary relapse (EMR). Herein, we present a case of a 46-year-old male patient who developed relapsed B-ALL with MLL-AF4. The patient initially achieved a complete remission (CR) after induction therapy and underwent haploidentical hematopoietic stem cell transplantation. Five months post-transplantation, he developed enlarged lymph nodes and subcutaneous masses. A lymph node biopsy confirmed EMR, without leukemia in the bone marrow or peripheral blood. The patient received the VCA regimen (venetoclax, chidamide, and azacitidine) and was regularly monitored through blood counts, marrow cell morphology analysis, flow cytometry, and computed tomography or positron emission tomography-computed tomography imaging. After the first VCA course, the patient achieved a second CR with only transient myelosuppression. Following two VCA courses, he received chimeric antigen receptor T-cell therapy, which led to complete metabolic remission and improved prognosis. This case underscores the potential of the VCA regimen as a bridging therapy for EMR in B-ALL with MLL-AF4, although further studies are warranted.

Keywords:  ALL; Bcl-2 inhibitor (venetoclax); MLL-AF4; demethylation (azacitidine); histone deacetylase inhibitor (chidamide); leukemia; relapsed/refractory; targeted therapy

DOI:  https://doi.org/10.3389/fimmu.2024.1475974
EJHaem. 2025 Feb;6(1): e1091

Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma-A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone.

Tobias S Slørdahl, Frida Bugge Askeland, Margrete Sofie Sætre Hanssen, Håkon Hov, Stine Marie Sundt-Hansen, Sofia Lindahl, Nils Tore Vethe, Henrik Hjorth-Hansen, Mona H Fenstad, Anders Waage, Øyvind Hjertner, Fredrik Schjesvold, Anders Sundan.

  Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination. Trial Registration: The study was registered at clinicaltrials.gov # NCT04163107.

Keywords:  autophagy; multiple myeloma; myeloma; myeloma therapy

DOI:  https://doi.org/10.1002/jha2.1091
Swiss Med Wkly. 2025 Jan 24. 155 3885

Blastic plasmacytoid dendritic cell neoplasm: a Swiss case series of a very rare disease and a structured review of the literature.

Ramona Meier-Lienhard, Cosima Suter, Thomas Pabst, Felicitas Hitz, Jakob R Passweg, Olivier Spertini, Nathan Cantoni, Daniel Betticher, Lucas Simeon, Michael Medinger, Stefanie Hayoz, Adrian Schmidt.

INTRODUCTION: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease, with unique diagnostic challenges and often dismal outcome. There are no widely accepted treatment guidelines available. Lymphoma-like regimens with or without autologous or allogenic transplantation were the cornerstone of most therapeutic concepts. A few years ago, the CD123-directed immunoconjugate tagraxofusp emerged as a new valuable treatment option. The goal of our research was to collect available data on BPDCN-patients treated at large centres in Switzerland and worldwide and to draw conclusions regarding the incidence, clinical presentation, prognostic factors and therapeutic strategies.
METHODS: We collected data from BPDCN patients from leading Swiss haemato-oncology centres from 2005 to 2022. Furthermore, we reviewed and analysed the published literature (cohorts and case reports in peer-reviewed journals) from 1997 to 2020 (structured review of the literature).
RESULTS: We identified 115 international publications including 600 patients from all over the world. Most of them had very small sample sizes (only ten papers with more than ten patients) and all but one were retrospective or observational respectively. Most included patients were Europeans (n = 385, 64%) and Asians (n = 120, 20%), followed by Americans (n = 90, 15%) and patients from Australia/New Zealand (n = 3) and Africa (n = 2). BPDCN was more common in men with a predominance of 3:1. The median age (n = 414) at diagnosis was 66.5 years ranging from one month to 103 years. Newly diagnosed women were significantly younger than men (median: 62 vs 67 years, mean: 53.4 vs 59.3 years, p = 0.027) and less often had bone marrow infiltration and affected lymph nodes. Upfront allogenic transplantation as well as ALL regimens performed best, with response to first-line therapy clearly associated with better overall survival. The Swiss cohort contained 26 patients (23 males and 3 females) over 18 years (2005-2022). The median age at diagnosis was 68.5 years (range: 20-83). Ten patients underwent upfront stem cell transplantation (seven allogenic and three autologous), at least trending towards a better overall survival than other therapies. With a follow-up of 8 years, the median overall survival was 1.2 years. Eight patients in this cohort were treated with tagraxofusp, which became available in 2020 and was approved by Swissmedic in 2023.
CONCLUSIONS: Our study confirms that BPDCN is a very rare and difficult-to-treat disease. Underdiagnosis and underreporting in the literature pose further challenges. Symptoms at presentation seem to differ slightly between sexes and reaching a complete remission after first-line treatment remains crucial for a prolonged overall survival. Effective treatment protocols in first line include transplantation regimens (mainly allogenic, potentially also autologous) as well as ALL protocols. In order to understand the significance of tagraxofusp as a bridge to transplant or as a continuous monotherapy in elderly patients, further evaluation with longer follow-up periods is required. In general, analysis of the Swiss patients confirmed the results from the worldwide cohort.

DOI: https://doi.org/10.57187/s.3885
Blood Adv. 2025 Jan 30. pii: bloodadvances.2024014840. [Epub ahead of print]

Six-month Rituximab-Lenalidomide regimen in advanced untreated Follicular Lymphoma: SAKK 35/10 Trial 10-year Update.

Eva K Kimby, Sämi Schär, Maria Cristina Pirosa, Anna Vanazzi, Ulrich J M Mey, Daniel Rauch, Björn E Wahlin, Felicitas Hitz, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés José María Jm Ferreri, Fatime Krasniqi, Michele Voegeli, Urban Novak, Thilo Zander, Hanne Bersvendsen, Christoph Mamot, Walter Mingrone, Anastasios Stathis, Stefan Dirnhofer, Stefanie Hayoz, Bjørn Østenstad, Emanuele Zucca.

The Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG) conducted the SAKK 35/10 randomized phase-2 trial (NCT0137605) to compare rituximab (R) alone versus R plus lenalidomide (L) as initial treatment for follicular lymphoma (FL). Patients with grade 1-3a FL, requiring systemic therapy, were randomized to either R (n=77; 375 mg/m2 IV x 1, weeks 1-4) or RL (n=77; R on the same schedule and L at 15 mg daily continuously). Responders (evaluated at 10 weeks) repeated R during weeks 12-15 with or without L (for a total of 18 weeks). Both arms had 47% of patients with a poor risk score on the FL International Prognostic Index (FLIPI). The primary endpoint, complete response (CR)/CR unconfirmed (CRu) rates at 6 months were superior with the combination, and now after a median follow-up of 9.5 years, have translated into a longer duration of response (DoR, median not reached vs 3.2 years; hazard ratio (HR)=0.42, 95% confidence interval (95%CI): 0.21-0.86; p=0.014), progression-free survival (PFS, 9.3 vs 2.3 years HR=0.57, 95% CI: 0.37-0.89; p=0.0128), and time-to-next treatment (TTNT, median not reached vs 2.1 years; HR=0.43, 95% CI: 0.27-0.67; p<0.001). Over 60% of RL responders remained in first CR at 10 years. OS was similar in both arms (77% vs 78% at 10 years, p=0.881). Toxicity was more common with RL but manageable. The SAKK 35/10 trial's long-term results confirmed a durable benefit of a short-term chemotherapy-free first-line RL regimen in symptomatic FL.

DOI: https://doi.org/10.1182/bloodadvances.2024014840
J Clin Med. 2025 Jan 10. pii: 392. [Epub ahead of print]14(2):

Tyrosine Kinase Inhibitor Therapy Enhances Stem Cells Profile and May Contribute to Survival of Chronic Myeloid Leukemiastem Cells.

Simone Rocco, Alessandro Maglione, Valentina Schiavo, Alessandro Ferrando, Carmen Fava, Daniela Cilloni, Barbara Pergolizzi, Cristina Panuzzo.

  Background/Objectives: Treatment with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has revolutionized disease management and has transformed CML from a life-threatening disease to a chronic condition for many patients. However, overcoming resistance, particularly related to leukemic stem cells (LSC) that can persist even when the bulk of the leukemic cells are eliminated, remains a significant challenge. Methods: K562 and KU812 cell lines were treated in vitro with the TKI Imatinib (IM). Gene expression, protein analysis, and metabolomic screening were conducted to investigate the ability of the drug to enhance stem cell (SC) features. Moreover, a gene ontology analysis was performed on different available datasets, to further consolidate our data. Results: 48 h of IM treatment can significantly increase the expression of genes related to SC self-renewal, particularly SOX2 and OCT 3/4. Interestingly, these modulations occur in cells that remain alive after drug treatment and that displayed features consistent with leukemia stem-like CML cells, suggesting that SC genes levels are crucial even in cell population survived upon TKI treatment. Moreover, after in silico analysis of available data, we observed an enrichment of SOX2/NANOG and OCT 3/4 signatures after TKI treatment, thus strengthening our results. Conclusions: Our results confirmed the relevance of LSC features after TKI treatment, highlighting the need for more effective and potentially curative strategies targeting LSCs to overcome resistance in CML.

Keywords:  FAO; OCT 3/4; ROS; SOX2; TKI; glutathione; leukemic stem cells (LSC); resistance

DOI:  https://doi.org/10.3390/jcm14020392
Exp Ther Med. 2025 Mar;29(3): 50

Successful treatment of a chronic myeloid leukemia patient with extreme thrombocytosis by a combination of imatinib and interferon‑α: A case report.

Meng-Xiao Jia, Da-Lin Di, Zhen-Zhen Liu, Hai-Ying Wang, Lei Chen.

  Chronic myeloid leukemia with extreme thrombocytosis (CML-T), defined by a platelet count >1,000x109/l is a rare leukemia subtype. The present case report described a 66-year-old female CML-T patient presenting with a platelet count of 3,798x109/l, but a consistently normal spleen size. Following treatment with imatinib combined with interferon-α, the patient achieved hematological remission within 2 months, with a platelet count reduction to 311x109/l and complete cytogenetic remission after 10 months. The patient experienced myocardial infarction and liver injury during treatment, which was managed with supportive care. The present case suggested that imatinib combined with interferon-α may be a safe and effective treatment option for patients with CML-T and extreme thrombocytosis and suboptimal response to imatinib monotherapy.

Keywords:  chronic myeloid leukemia with thrombocytosis; imatinib; interferon-α; thrombocytosis

DOI:  https://doi.org/10.3892/etm.2025.12800
Clin Genitourin Cancer. 2025 Jan 06. pii: S1558-7673(25)00001-1. [Epub ahead of print] 102299

Primary Renal Lymphoma: A Single-Center Study of 14 Cases.

Tao Wang, Yunxia An, Hongyun Zhai, Houming Zhao, Xiaohui Ding.

   OBJECTIVE: To investigate the clinical characteristics, pathology, imaging features, and prognosis of primary renal lymphoma (PRL), a rare malignancy.
PATIENTS AND METHOD: We conducted a retrospective review of 14 PRL cases diagnosed between January 2009 and January 2022, with follow-up data collected from medical records.
RESULTS: The study included 14 patients (7 males, 7 females), with a mean age of 60.4 years. All cases were unilateral, with 6 involving the left kidney and 8 the right. Eleven patients underwent radical nephrectomy, and two had partial nephrectomy. Pathological subtypes included 8 cases of diffuse large B-cell lymphoma (DLBCL), 5 of extranodal marginal zone B-cell lymphoma (MZBL), and 1 of extranodal NK/T-cell lymphoma. Nine patients received 4-6 cycles of adjuvant chemotherapy: 4 with the R-CHOP regimen, 4 with CHOP, and 1 with COP-L combined with chidamide for extranodal NK/T-cell lymphoma. By June 2022, 7 patients were alive, while 7 had died, 5 of whom did not receive adjuvant chemotherapy. The median progression-free survival (PFS) was 33 months, and the median overall survival (OS) was 38 months.
CONCLUSIONS: PRL is a rare lymphoma, with diffuse large B-cell lymphoma (DLBCL) being the most common subtype. Nephrectomy followed by R-CHOP chemotherapy is recommended as the treatment approach, and early diagnosis is essential for improving patient outcomes.

Keywords:  Chemotherapy; DLBCL; Nephrectomy; PRL; Prognosis

DOI:  https://doi.org/10.1016/j.clgc.2025.102299