The evidence
Every number on this site, and where it comes from.
Independent, peer-reviewed sources are listed first. Company-reported data are marked as such and kept separate. Where the literature is thin or single-arm, we say so. Last reviewed September 2026.
Basics
Definitions, ranges, grades, cost
Mayo Clinic Laboratories, CBC with differential
Adult absolute lymphocyte reference range printed on the test catalog. Other labs use 850 or 1,000 as the lower limit; always use the range on your own report.
Cleveland Clinic, Lymphopenia and Lymphocytes
Normal adult range about 1,000–4,800 cells/µL; lymphocytes are roughly 20–40% of white blood cells; lymphopenia in adults is a count below 1,000.
clevelandclinic.org/lymphopenia · clevelandclinic.org/lymphocytes
NCI Common Terminology Criteria for Adverse Events v5.0
"Lymphocyte count decreased": grade 1 <LLN to 800/mm³; grade 2 <800–500; grade 3 <500–200; grade 4 <200/mm³. The scale every U.S. oncology trial uses.
Medicare Clinical Laboratory Fee Schedule, CBC with automated differential
The national Medicare payment for the test that already contains the absolute lymphocyte count. No new test is needed to monitor it.
Prognosis
Lymphopenia predicts survival
Ray-Coquard et al., Cancer Research 2009
322 non-Hodgkin lymphoma, 287 metastatic breast, 193 advanced sarcoma. Baseline lymphopenia (<1,000/µL) in about a quarter of each group, and an independent predictor of shorter survival in all three: lymphoma 11 vs 94 months, breast 10 vs 14, sarcoma 5 vs 10. Often misquoted as 3,000 patients; the paper reports 802.
Ray-Coquard et al., British Journal of Cancer 2001
Day-1 lymphocyte count ≤700/µL before chemotherapy tripled the hazard of early death (95% CI 1.6–5.8). Patients with lymphopenia and poor performance status had a 20% early-death rate versus 1.7% with neither.
Grossman et al., JNCCN 2015
Glioma, resected and unresectable pancreatic, and lung cancer. 83% started normal; median count fell 63% (1,481 → 560) by two months; 43% reached grade 3–4, which doubled the hazard of death (95% CI 1.54–2.78). Median count stayed under 1,000 for the full year of follow-up. By tumor: glioma 1.8, resected pancreas 2.2, unresectable pancreas 2.9, lung 1.7.
Grossman et al., Clinical Cancer Research 2011
96 high-grade glioma patients on radiation plus temozolomide. 40% had CD4 below 200 at two months; their median survival was 13.1 vs 19.7 months (P = 0.002). 88% of deaths were from tumor progression, 2.5% from infection.
Damen et al., Int J Radiation Oncology Biology Physics 2021
Systematic review and meta-analysis of severe radiation-induced lymphopenia. Grade ≥3 vs 0–2: pooled adjusted HR for death 1.65 (95% CI 1.43–1.90). Brain 1.63, lung 1.52, pancreas 1.92.
Venkatesulu et al., Future Oncology 2022
Severe lymphopenia after radiotherapy for pancreatic cancer: pooled HR 2.33 (95% CI 1.79–3.03); mean survival 6.8 months shorter. Proposes a mean spleen dose under 9 Gy.
Glioma meta-analysis, 2021
Severe treatment-related lymphopenia in 31.6%; hazard of death 1.99 (95% CI 1.74–2.27) in 819 evaluable patients; glioblastoma subgroup 2.00.
Balmanoukian et al., Cancer Investigation 2012
53 patients after pancreatic resection and chemoradiation. Counts fell 63%; 45% were under 500 at two months; median survival 14 vs 20 months (p = 0.048); multivariate HR 2.20.
Metastatic colorectal cohort, 2011
260 patients; baseline lymphopenia in 19%; response rate 12.5% vs 40.2%; survival 16 vs 24 months (P = 0.024).
Eberst et al., BMC Cancer 2022
169 non-small-cell lung cancer patients. CD4 under 500 in 28.4%; survival 16.1 vs 21.7 months; HR 1.616 (95% CI 1.1–2.36).
Treatment effects
Chemotherapy and radiation lower the count, for a long time
Sandul et al., Clinical and Translational Radiation Oncology 2025
142 lymphocyte-count curves from 52 publications. Counts fell to a median 24% of baseline by the end of radiotherapy and had recovered to only 55% at one year.
Hong et al., BMC Cancer 2013
243 stage II/III colorectal patients. Lymphopenia during FOLFOX in 42.8%; a nadir below 0.66 × 10⁹/L carried a disease-free-survival HR of 3.52 (95% CI 1.70–7.28). The regimen Beth received.
Noh et al., World Journal of Surgery 2017
231 colon cancer patients on FOLFOX. Low lymphocyte count during chemotherapy: 5-year disease-free survival 61.9% vs 76.7%; HR 1.83 (95% CI 1.10–3.05).
Verma et al., Breast Cancer Research 2016
88 breast cancer patients. B cells fell to 5.4% of baseline two weeks after chemotherapy; at nine months B cells were 69% and CD4 T cells 60% of baseline, while CD8 and NK cells recovered.
Campian et al., Cancer Investigation 2013
47 patients; 67% drop; 49% below 500. Survival difference (21.8 vs 27.3 months) did not reach significance in this small cohort; the authors note lymphopenia "persists for months to years."
Immunotherapy
A low count blunts checkpoint inhibitors
Ismail et al., Cancers 2026
TriNetX real-world analysis; 5,249 per group after propensity matching. Baseline ALC below 1.5 × 10⁹/L: 24-month survival 27.9% vs 35.3%. Authors recommend adding baseline ALC to routine pre-immunotherapy risk assessment.
Goldschmidt et al., Cancer Medicine 2023
Melanoma, lung and kidney cancer patients on checkpoint inhibitors. Higher baseline lymphocyte count was independently associated with better survival (p < 0.0001 in lung).
Conroy et al., BJC Reports 2024
179 patients. Lymphopenia three months into immunotherapy halved median survival (p < 0.001); prior radiotherapy was the strongest risk factor for developing it.
NSCLC PD-1/PD-L1 cohort, 2019
142 patients; baseline count above 0.93 × 10⁹/L cut the hazard of death by 62% (95% CI 0.23–0.62).
Ménétrier-Caux et al., Journal for ImmunoTherapy of Cancer 2019
Review. Lymphopenia in more than 20% of advanced-disease patients versus about 3% with localized disease. States that while neutrophils, platelets and red cells are routinely monitored, the ALC is "rarely analyzed and never used to choose therapy or as prognostic criteria." Recovery of a normal count is associated with response to checkpoint inhibitors.
Beyond cancer
The count matters in sepsis, COVID-19 and the general population
Zidar et al., JAMA Network Open 2019 (NHANES)
ALC ≤1,000/µL in 3.0% of adults without a cancer diagnosis; all-cause mortality HR 1.8 (95% CI 1.6–2.1). ≤1,500 in 20.1%, HR 1.3.
Warny et al., PLoS Medicine 2018 (Copenhagen General Population Study)
Lymphopenia (<1.1 × 10⁹/L) raised the risk of any infection 41%, infection-related death 70%, and sepsis 51%.
Drewry et al., Shock 2014
335 septic patients. Severe persistent lymphopenia on day 4 (≤0.6 × 10⁹/L): 28-day mortality 39.5% vs 10.4% without; one-year mortality 57.9% vs 28.8%.
Zhao et al., International Journal of Infectious Diseases 2020
Meta-analysis, 13 studies, 2,282 patients. Lymphopenia tripled the odds of severe disease (95% CI 1.31–6.82). A CDC-journal meta-analysis found the same direction (Huang & Pranata, EID 2020).
Guidelines
What the rulebooks say
NCCN Guidelines, Hematopoietic Growth Factors (v1.2025)
Addresses neutropenia (G-CSF), chemotherapy-induced thrombocytopenia and anemia. No lymphocyte-count recommendations on the guideline page or in the published JNCCN summary (Griffiths et al., 2022).
ASCO/IDSA, Outpatient Management of Fever and Neutropenia, JCO 2018
Defines severe (<500/µL) and profound (<100/µL) neutropenia with explicit management pathways. Contains no lymphocyte thresholds.
U.S. national oncology guideline setting an ALC threshold
In the sources reviewed for this site, none was found that sets an absolute lymphocyte count threshold for monitoring, dose modification or treatment of treatment-related lymphopenia. The only lymphopenia-specific pathway located was a UK regional primary-care sheet outside oncology (NHS SWAG). If you know of one, please send it.
Absence claim; scope: NCCN growth-factor guidance, ASCO/IDSA neutropenia guidance, targeted searches, September 2026.
Anktiva & FDA
Regulatory record and company-reported data
Entries marked company come from the manufacturer's press releases and have not been peer-reviewed. They are included for completeness and should be weighed accordingly. For the mechanism in plain language, the physician interviews and the patient accounts, see How Anktiva works.
FDA approval, April 22, 2024
Nogapendekin alfa inbakicept-pmln with BCG for BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ. Complete response 62% (95% CI 51–73); 58% of responses lasted ≥12 months, 40% ≥24 months. Label: intravesical use only.
Chamie et al., NEJM Evidence 2023 (QUILT-3.032)
Peer-reviewed report of the pivotal bladder cancer cohort: complete response 71%, median duration 26.6 months.
Margolin et al., Clinical Cancer Research 2018
Phase 1 trial of the molecule (then ALT-803) in solid tumors: expansion of NK cells and CD8+ T cells within a week of the first subcutaneous dose, without expanding regulatory T cells.
FDA Expanded Access authorization, lymphopenia company
For relapsed or refractory solid tumors with ALC below 1,000/µL. Expanded access permits use outside a trial; it is not approval and does not establish efficacy.
QUILT-88, ASCO 2025 company
Third-line-plus pancreatic cancer. Patients whose lymphopenia reversed had an overall-survival HR of 0.46 (95% CI 0.26–0.80) versus those whose did not. A responder analysis, not a randomized comparison; subject to immortal-time bias.
QUILT-3.078, recurrent glioblastoma company
Mean ALC rose from 0.9 to at least 1.4 × 10³/µL within one treatment cycle (p < 0.001); median overall survival not yet reached at report. Single-arm, small, company-reported.
Supplemental BLA, papillary-only NMIBC company
Accepted for standard review; decision date January 6, 2027.
FDA Warning Letter to ImmunityBio
Concerns promotional claims. Cited here for completeness and because it is the reason this site relies on the label and the literature rather than company marketing.
Anktiva price guide
Approximate wholesale list price per 400 µg vial. Actual patient cost depends on coverage; the third policy request on this site concerns Medicare coverage with evidence development.
Using this list
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