To evaluate the long-term outcome of dose density chemotherapy in the treatment of aggressive lymphoma, we analyzed 142 patients with untreated aggressive lymphoma. Chemotherapy was an eight-drug regimen given in weekly intervals in two prospective trials. The median observation period was 8 years; the longest follow-up was 13 years. Overall survival at 8 years was 0.583. The 8-year survival of patients < or =60 years was significantly better than that of older patients, namely 0.713 vs 0.304 (p=0.000000697). This excellent survival of patients aged < or =60 years was identical for high-risk and high-intermediate-risk patients compared with low-risk and low-intermediate-risk patients in the age-adjusted international prognostic index (IPI). The excellent long-term results of the CEOP/IMVP-Dexa regimen (cyclophosphamide, epirubicin, vincristine, and prednisone/ifosfamide with systemic mesna, methotrexate, etoposide, and dexamethasone) for patients aged < or =60 years suggest that this regimen might be superior to the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and needs to be tested in comparison to high-dose regimens and novel approaches including antibody treatment.
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http://dx.doi.org/10.1007/s00277-004-0936-x | DOI Listing |
Nat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFCell Rep Med
January 2025
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:
Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138 cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models.
View Article and Find Full Text PDFBr J Radiol
January 2025
Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, 110029.
Background: Research into the intratumoral microenvironment in lymphoma has been escalated along with improved survival and new targeted therapies with an intent to refine risk stratification and prognostication. Various studies have reported significance of quantitative DCE-MRI parameters for predicting biological behaviour of various tumors. This study is an endeavour to supplement the existing literature on quantitative DCE-MRI in nodal lymphoma.
View Article and Find Full Text PDFJ Med Chem
January 2025
College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, China.
The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound () was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC) = 112 ± 8 nM] and BRD4-BD1 (IC = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells.
View Article and Find Full Text PDFAm J Dermatopathol
February 2025
Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
Methotrexate (MTX), an antimetabolite targeting certain autoimmune conditions and various hematologic malignancies, has been associated with iatrogenic lymphoproliferative disease (LPD) primarily of B-cell lineage. Less commonly are T-cell neoplasms where primary skin involvement is considered rare. Three cases were encountered in the medical practice of one of the authors.
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