Smalley, R V, Anderson, S A, Tuttle, R L et al. · Blood · 1991
This study tested two different doses of interferon-alpha (a type of immune protein) in patients with hairy cell leukemia, a blood cancer. Researchers found that the lower dose worked almost as well as the higher dose for improving blood cell counts but caused fewer side effects, including less chronic fatigue. Based on these results, doctors were advised to start patients on the lower dose.
This study is relevant to ME/CFS research because it documents chronic fatigue syndrome as a quantifiable adverse effect of interferon-alpha therapy, providing clinical data on interferon-associated fatigue in a controlled setting. Understanding interferon's role in fatigue may inform mechanistic investigations into whether similar immune dysregulation contributes to ME/CFS pathophysiology.
This study does not establish that interferon-alpha causes ME/CFS in the general population—it describes fatigue as a side effect in cancer patients receiving acute, high-dose therapy. The fatigue observed here may differ mechanistically from ME/CFS and does not prove that interferon dysregulation is the primary driver of ME/CFS in non-treated populations. Correlation between interferon exposure and fatigue does not establish causation of the disease itself.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Smalley, R V, Anderson, S A, Tuttle, R L, Connors, J, Thurmond, L M, Huang, A, et al. (1991). A randomized comparison of two doses of human lymphoblastoid interferon-alpha in hairy cell leukemia. Wellcome HCL Study Group.. Blood. https://pubmed.ncbi.nlm.nih.gov/1742480/
BibTeX
@article{mecfsatlas-smalley-1991-randomized-comparison,
author = {Smalley, R V and Anderson, S A and Tuttle, R L and Connors, J and Thurmond, L M and Huang, A and Castle, K and Magers, C and Whisnant, J K},
title = {A randomized comparison of two doses of human lymphoblastoid interferon-alpha in hairy cell leukemia. Wellcome HCL Study Group.},
journal = {Blood},
year = {1991},
note = {PubMed: 1742480},
url = {https://www.mecfsatlas.com/evidence/smalley-1991-randomized-comparison},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/smalley-1991-randomized-comparison
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