Chemotherapy for Non-Cancer Conditions: Rare Indications and Strict Criteria

Chemotherapy (cytotoxic/immunomodulatory drugs) is primarily anticancer. However, specific agents are used off-label or FDA-approved for severe, refractory non-malignant diseases where immune dysregulation or abnormal cell proliferation drives pathology.

Established Non-Oncology Uses

1. Autoimmune Diseases:
   • Methotrexate (MTX): Anchor drug for RA, psoriasis, JIA, SLE (low-dose, weekly).
   • Cyclophosphamide: Severe SLE nephritis, vasculitis (granulomatosis with polyangiitis), myositis.
   • Azathioprine, Mycophenolate: Steroid-sparing in SLE, IBD, autoimmune hepatitis.
   • Rituximab (anti-CD20): RA, ANCA vasculitis, pemphigus, ITP (not classic chemo but biologic).
2. Transplant Immunosuppression:
   • Cyclophosphamide, azathioprine, MMF, tacrolimus (calcineurin inhibitor) prevent rejection.
3. Hematologic Disorders (Non-Malignant):
   • Aplastic Anemia: IST (ATG + cyclosporine) or cyclophosphamide-based regimens.
   • Sickle Cell Disease: Hydroxyurea (ribonucleotide reductase inhibitor) ↑ HbF.
   • ITP/Thrombotic Microangiopathies: Rituximab, caplacizumab.
4. Severe Inflammatory/Infectious:
   • Cytokine Storm (HLH, CAR-T toxicity, severe COVID-19): Anakinra, tocilizumab, etoposide (HLH-94/2004 protocol).
   • Refractory Infections: Rare—adjunctive immunomodulation (e.g., steroids, not classic chemo).

Critical Principles

• Risk-Benefit: Cytopenias, infection, infertility, secondary malignancy, organ toxicity.
• Specialist Management: Rheumatology, hematology, transplant, immunology.
• Not "Chemotherapy" in Patient Perception: Dosing, schedules, and goals differ radically from cancer protocols.
• Informed Consent: Must address off-label use, fertility preservation, long-term surveillance.

These are highly individualized decisions. "Chemotherapy for non-cancer" is a misnomer—better termed immunomodulatory or cytotoxic therapy for immune-mediated disease.