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Cited by 657Chronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and TreatmentMonoclonal and Polyclonal Antibodies Research

The DOI matches its Crossref record; 22 of the 23 references it cites were found in a registry or an index.

Cytokine-Release Syndrome in Patients With B-Cell Chronic Lymphocytic Leukemia and High Lymphocyte Counts After Treatment With an Anti-CD20 Monoclonal Antibody (Rituximab, IDEC-C2B8)

Winkler, U., Jensen, M., Manzke, O., Schulz, H., Diehl, V., Engert, A.·1999·Blood
DOI 10.1182/blood.v94.7.2217.419k02_2217_2224
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Abstract

Eleven patients with relapsed fludarabine-resistant B-cell chronic lymphocytic leukemia (CLL) or leukemic variants of low-grade B-cell non-Hodgkin’s lymphoma (NHL) were treated with the chimeric monoclonal anti-CD20 antibody rituximab (IDEC-C2B8). Peripheral lymphocyte counts at baseline varied from 0.2 to 294.3 × 109/L. During the first rituximab infusion, patients with lymphocyte counts exceeding 50.0 × 109/L experienced a severe cytokine-release syndrome. Ninety minutes after onset of the infusion, serum levels of tumor necrosis factor- (TNF-) and interleukin-6 (IL-6) peaked in all patients. Elevated cytokine levels during treatment were associated with clinical symptoms, including fever, chills, nausea, vomiting, hypotension, and dyspnea. Lymphocyte and platelet counts dropped to 50% to 75% of baseline values within 12 hours after the onset of the infusion. Simultaneously, there was a 5-fold to 10-fold increase of liver enzymes, d-dimers, and lactate dehydrogenase (LDH), as well as a prolongation of the prothrombin time. Frequency and severity of first-dose adverse events were dependent on the number of circulating tumor cells at baseline: patients with lymphocyte counts greater than 50.0 × 109/L experienced significantly more adverse events of National Cancer Institute (NCI) grade III/IV toxicity than patients with less than 50.0 × 109/L peripheral tumor cells (P= .0017). Due to massive side effects in the first patient treated with 375 mg/m2 in 1 day, a fractionated dosing schedule was used in all subsequent patients with application of 50 mg rituximab on day 1, 150 mg on day 2, and the rest of the 375 mg/m2 dose on day 3. While the patient with the leukemic variant of the mantle-cell NHL achieved a complete remission (9 months+) after treatment with 4 × 375 mg/m2 rituximab, efficacy in patients with relapsed fludarabine-resistant B-CLL was poor: 1 partial remission, 7 cases of stable disease, and 1 progressive disease were observed in 9 evaluable patients with CLL. On the basis of these data, different infusion schedules and/or combination regimens with chemotherapeutic drugs to reduce tumor burden before treatment with rituximab will have to be evaluated.

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Crossref · 10.1182/blood.v94.7.2217.419k02_2217_2224

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  1. O’Brien, 1998, Phase I/II study of rituxan in chronic lymphocytic leukemia (CLL)., Blood, 92, 105a

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Metadata

Authors
Winkler, U., Jensen, M., Manzke, O., Schulz, H., Diehl, V., & Engert, A.
Affiliations
University of Cologne (DE)
ORCID
Engert, A.
Venue
Blood
Publisher
American Society of Hematology
Published
1999-10-01
Volume
94
Issue
7
Pages
2217-2224
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v94.7.2217.419k02_2217_2224
OpenAlex
W1685882185
Cited by
657
References
23
Citations by year
2026: 6 · 2025: 14 · 2024: 21 · 2023: 19 · 2022: 26 · 2021: 28 · 2020: 35 · 2019: 27 · 2018: 17 · 2017: 30 · 2016: 15 · 2015: 16 · 2014: 21 · 2013: 21 · 2012: 16
FWCI
17.59
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
cytokine release syndrome, rituximab, anti-CD20 monoclonal antibody, chronic lymphocytic leukemia, relapsed CLL, non-Hodgkin lymphoma, TNF-α, interleukin-6, infusion toxicity, dose fractionation, circulating tumor cells, mantle cell lymphoma, fludarabine resistance
MeSH terms
Rituximab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Female, Humans, Liver Function Tests, Male, Middle Aged, Neoplasm Staging, Platelet Count, Syndrome, Tumor Necrosis Factor-alpha, Leukemia, Lymphocytic, Chronic, B-Cell, Interleukin-6, Cytokines, Lymphocyte Count, Antigens, CD20, Lymphoma, Mantle-Cell, Antibodies, Monoclonal, Murine-Derived

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