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. These are historical v5.0 bands. CTCAE v6.0 instead lists lymphopenia as grade 1, present; do not treat these v5.0 bands as universal current trial or treatment rules.
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
In 1,051 patients, day-1 lymphocyte count ≤700/µL was independently associated with death within one month of chemotherapy (reported estimate 3.1, 95% CI 1.6–5.8; labeled HR in the paper's logistic-regression analysis). The model-estimated early-death probability was 20% with both lymphopenia and performance status >1, 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 was associated with a higher 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
Review of 142 curves from 52 publications. Median counts at treatment completion were 24% of baseline for intracorporeal radiotherapy and 10% for extracorporeal blood irradiation. Among 34 studies reporting recovery, the median reached 55% of baseline within 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 was associated with lower 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 was associated with better survival (HR 0.38) (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 in the NHANES cohort; age- and sex-adjusted 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) was associated with higher hazards of any infection (HR 1.41), infection-related death (HR 1.70) and sepsis (HR 1.51).
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
Review of 13 studies involving 2,282 patients. Five studies contributed to the pooled association between lymphopenia and severe disease (OR 2.99, 95% CI 1.31–6.82). A separate meta-analysis also associated lower lymphocyte counts with severe illness (Emerging Infectious Diseases, 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.
Treatment-specific guidance and the remaining research gap
Our earlier statement that no monitoring or treatment thresholds exist was too broad. Temozolomide labeling includes lymphopenia monitoring and infection-prevention instructions. The unresolved question is when lymphocyte-restoring treatment improves outcomes across solid tumors. Regional primary-care guidance also exists (NHS SWAG). Please send additional guidance.
Scope: selected supportive-care guidelines and drug labeling, reviewed September 2026. This is not an exhaustive guideline review. · FDA / TEMODAR
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 ALT-803 in 24 patients with advanced solid tumors: NK-cell expansion and early CD8 T-cell activation, with modest circulating CD8 count increases. Regulatory T cells increased in one of seven evaluable patients. No objective tumor responses occurred.
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.
FDA expands Anktiva + BCG approval
October 14, 2026: The FDA expanded Anktiva plus BCG to include adults with BCG-unresponsive, high-grade papillary-only non-muscle-invasive bladder cancer. This broadens the previous indication, which required carcinoma in situ (CIS), with or without papillary tumors. (FDA announcement)
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
An advertised cash-price estimate per 400 µg vial, not wholesale acquisition cost or a patient's out-of-pocket bill. Pricing varies by date, provider, coverage and assistance.
Using this list
Everything here may be reproduced with attribution. Cite the original paper, not this site. The full research dossier that produced this page is available on request through the contact form. Corrections are welcome and will be acknowledged on this page.