Busulfan
Myleran · Alkylator
Conditioning-regimen TMA risk.
TMA
ModerateOpen →
Antitumor antibiotic
Mitomycin C
Mutamycin · MMC
The prototype dose-dependent TMA — risk climbs past a cumulative threshold.
SevereAntitumor antibiotic · approved 1974
GastrointestinalBladder (intravesical)Anal
Signature kidney injury
Thrombotic Microangiopathy
Representative incidence10%
Dose-dependent, generally 4–15%; risk rises sharply at cumulative dose ≥30 mg/m². >50% historical mortality.
Source: Lesesne et al., J Clin Oncol 1989
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeveritySevere
ReversibilityOften irreversible
Evidence0 refs
Nephron map
GlomerulusFiltration barrier (podocytes + endothelium)
Vasculature / EndotheliumGlomerular & peritubular capillaries
Thrombotic Microangiopathy
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.
Mechanism of kidney injury
Direct cumulative endothelial toxicity drives a systemic thrombotic microangiopathy — the classic dose-related drug-induced TTP/HUS.
Clinical presentation
Microangiopathic hemolytic anemia, thrombocytopenia and AKI, often with pulmonary edema; high historical mortality.
Onset
Delayed — after cumulative dosing, sometimes after therapy ends.
Reversibility
Often irreversible
Anticancer mechanism
Antitumor antibiotic that cross-links DNA after bioreductive activation. GI, intravesical bladder and anal cancers.
Management
Discontinue, supportive care, dialysis; eculizumab in selected cases. Plasma exchange has limited benefit.
Risk factors
- Cumulative dose ≥30–60 mg/m²
- Concurrent 5-fluorouracil
Prevention
- Cumulative-dose limits
- Monitoring / awareness
Note · The prototype of dose-dependent drug-induced TMA.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Thrombotic MicroangiopathyGlomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of antitumor antibiotics.
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Mitomycin / bleomycin pulmonary toxicity
Hematologic
Cytopenias, thrombosis, TMA
- Cumulative myelosuppression
Evidence
5 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkCancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry.Lesesne JB et al. · J Clin Oncol 1989 · PMID 2497229Definitive registry: MMC in 84/85, dose-dependent 4–15% risk, >50% mortality.PMIDCarcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy.Cantrell JE et al. · J Clin Oncol 1985 · PMID 3923162Landmark series first defining MMC-associated TMA/HUS.PMIDThrombotic microangiopathy with targeted cancer agents.Blake-Haskins JA et al. · Clin Cancer Res 2011 · PMID 21813634Contrasts classic chemotherapy TMA with often-reversible targeted-agent TMA.PMIDAntineoplastic agents and thrombotic microangiopathy.Garcia G et al. · J Oncol Pharm Pract 2016 · PMID 26854265Focused review covering mitomycin C and gemcitabine TMA.PMIDDrug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.Mazzierli T et al. · Front Pharmacol 2023 · PMID 36699080Up-to-date DITMA synthesis including mitomycin.
Related agents
Other agents sharing the same signature kidney injury.