Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma

Khashab, Tamer; Hagemeister, Fredrick B.; Romaguera, Jorge; Fanale, Michelle A.; Pro, Barbara; McLaughlin, Peter; Rodriguez, Maria Alma; Neelapu, Sattva S.; Fayad, Luis; Younes, Anas; Feng, Lei; Vega, Francisco; Kwak, Larry W.; Samaniego, Felipe

doi:10.1111/bjh.15814

Cited by 7 publications

(2 citation statements)

References 42 publications

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“…As a purine analogue and a strong adenosine deaminase inhibitor, pentostatin has been widely used as an anti-lymphocyte treatment, particularly in patients with T-PLL and hairy cell leukemia (17,18). There has been greater research recently, however, to expand indications for pentostatin, including cutaneous T-cell lymphomas and marginal zone lymphoma, with similar reports of high tolerability by patients (19,20). Our patient did not tolerate his first two rounds of chemotherapy well, experiencing adverse effects that include cerebellar toxicity and infusion reactions thus requiring individualized adjustment of his treatment.…”

Section: Discussionmentioning

confidence: 99%

Complete remission of aggressive T-cell LGL leukemia with pentostatin therapy: first case report

2020

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This is the first report of a complete remission in aggressive T-cell large granular lymphocytic (T-LGL) leukemia after treatment with pentostatin. The aggressive variant of the disease is rare, and traditional therapies include immunosuppressive agents, however, there is no standard consensus for treatment. Cytotoxic chemotherapy has led to remission in a few reported cases. We present this unique case as an alternative treatment for individuals refractory to chemotherapy. A 55-year-old African American male with hypertension, type II diabetes mellitus, hyperlipidemia, and gout presented with symptoms of multiple ecchymosis, fatigue, and weight loss. He was found to have splenomegaly (SM) and significant leukocytosis to 101 k/μL with 30% blasts on peripheral smear. Following bone marrow aspiration and biopsy with flow cytometry, he was diagnosed with aggressive T-LGL leukemia. The chemotherapy regimen hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) was initially chosen based on his clinical presentation but was refractory to treatment. His therapy was changed to alemtuzumab; however, patient tolerated poorly and did not respond. Pentostatin was added to alemtuzumab with improvement in clinical symptoms and laboratory parameters. The patient was transitioned to pentostatin monotherapy and achieved complete remission after 1 month. This report provides support for pentostatin as an effective treatment for patients with aggressive T-cell malignancies refractory to cytotoxic chemotherapy. Pentostatin has previously been studied to treat T-cell prolymphocytic leukemia (T-PLL), hairy cell leukemia, and marginal zone lymphoma. This case suggests an alternative, well-tolerated option that could be considered for initial therapy of aggressive T-LGL leukemia.

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Section: Discussionmentioning

confidence: 99%

Complete remission of aggressive T-cell LGL leukemia with pentostatin therapy: first case report

2020

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“…Serum beta 2 -microglobulin (sβ 2 m) is a well-established prognostic factor in multiple myeloma, and has been incorporated in the international staging system (ISS) [31]. It is also an extensively evaluated prognostic factor in diffuse large B-cell lymphoma and other non-Hodgkin lymphoma subtypes [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] and may work in acute myeloid leukemia as well [47], but has not been incorporated in current prognostic models for these diseases. Although tested as a prognostic factor in HL 30 years ago [48], its role has not yet been fully established; thus, sβ 2 m has not been used in any of the current prognostic systems for HL.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients

Vassilakopoulos,

Arapaki,

Diamantopoulos

et al. 2024

Cancers

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The significance of serum beta-2 microglobulin (sβ2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8–3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff (“normal versus high”). In multivariate analysis, sβ2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a “normal versus high” cutoff set at 2.4 mg/L.

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DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

Huang

Zhou

2021

Sig Transduct Target Ther

421

202

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Genomic instability is the hallmark of various cancers with the increasing accumulation of DNA damage. The application of radiotherapy and chemotherapy in cancer treatment is typically based on this property of cancers. However, the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy. Targeted cancer therapy has the potential to suppress cancer cells’ DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions. Obviously, understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy, in particular, raising novel hypothesis or theory in this field on the basis of previous scientists’ findings would be important for future promising druggable emerging targets. In this review, we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed, then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy, highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors, also, the DNA damage baseline drift leads to the harmful intrinsic targeted cancer therapy. In addition, clinical therapeutic drugs for DNA damage and repair including therapeutic effects, as well as the strategy and scheme of relative clinical trials were intensive discussed. Based on this background, we suggest two hypotheses, namely “environmental gear selection” to describe DNA damage repair pathway evolution, and “DNA damage baseline drift”, which may play a magnified role in mediating repair during cancer treatment. This two new hypothesis would shed new light on targeted cancer therapy, provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for patients.

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Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma

Cited by 7 publications

References 42 publications

Complete remission of aggressive T-cell LGL leukemia with pentostatin therapy: first case report

Complete remission of aggressive T-cell LGL leukemia with pentostatin therapy: first case report

Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients

DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

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