Busulfan
Myleran · Alkylator
Conditioning-regimen TMA risk.
TMA
ModerateOpen →
Immunotoxin (anti-CD22 PE38)
Moxetumomab pasudotox
Lumoxiti · MOXE
An anti-CD22 Pseudomonas-exotoxin immunotoxin with a boxed warning for capillary leak and hemolytic-uremic syndrome.
SevereAnti-CD22 immunotoxin (PE38) · approved 2018
Relapsed or refractory hairy-cell leukemia after at least two prior systemic therapies, including a purine nucleoside analog
Signature kidney injury
Thrombotic Microangiopathy
Representative incidence7.5%
Boxed warning for capillary-leak syndrome (CLS) and hemolytic-uremic syndrome (HUS)/TMA. In the pivotal phase 3 trial HUS occurred in ~7.5% and CLS in ~5%; reviews cite roughly 9% each. Fatal CLS has been reported (in a pediatric ALL case).
Source: Kreitman et al., Leukemia 2018
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeveritySevere
ReversibilityReversible
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
Two distinct vascular mechanisms. HUS/TMA: toxin-mediated endothelial injury produces glomerular microangiopathy with microthrombi, mechanical red-cell shearing (schistocytes) and platelet consumption, causing AKI. CLS: toxin- and cytokine-mediated capillary permeability leads to fluid/protein extravasation, intravascular volume depletion and prerenal/hypovolemic AKI.
Clinical presentation
HUS triad — microangiopathic hemolytic anemia (schistocytes, high LDH, low haptoglobin), thrombocytopenia and a rising creatinine. CLS — hypotension, edema, weight gain, hypoalbuminemia and hemoconcentration. HUS classically emerges during/after cycles 2-3 (anamnestic), CLS within the first days of a cycle.
Onset
Cycle-related: CLS within the first days of a cycle; HUS often during/after cycles 2-3.
Reversibility
Reversible
Anticancer mechanism
Recombinant immunotoxin joining an anti-CD22 Fv fragment to PE38, a truncated Pseudomonas exotoxin A. Binding to CD22 on hairy-cell leukemia cells drives internalization; the toxin then ADP-ribosylates elongation factor 2 (eEF2), halting protein synthesis and triggering apoptosis. Hairy-cell leukemia is exquisitely sensitive owing to high CD22 density.
Management
For CLS: hold the drug, give IV fluids and albumin, and add corticosteroids. For HUS/TMA: discontinue (do not retreat), provide supportive care with transfusion and dialysis as needed; plasma exchange and eculizumab are not established for this drug-induced TMA. Most hairy-cell-leukemia events are reversible with supportive care.
Risk factors
- Higher cumulative dose/exposure and repeat cycles
- Pre-existing renal impairment (avoid initiating if CrCl <30 mL/min)
- Volume depletion
Prevention
- Adequate IV/oral hydration before and after each infusion
- Do not initiate if CrCl <30 mL/min
- Consider low-dose aspirin thromboprophylaxis per label; antihistamine/antipyretic premedication
- Monitor hemolysis labs and weight/BP each cycle
Note · Voluntarily withdrawn from the US market in 2023 for commercial (not safety) reasons; the renal mechanism and boxed-warning data remain reference-grade.
Clinical depth
Renal dose adjustment
Do not initiate if CrCl <30 mL/min. Hold for serious CLS or HUS; permanently discontinue for HUS or recurrent serious CLS. No simple CrCl-based dose scaling otherwise.
Dialyzability & ESKD dosing
Not characterized — dialysis supports AKI/HUS rather than clearing the immunotoxin.
Differential diagnosis
Distinguish from other drug-induced TMA (gemcitabine, calcineurin inhibitors, mitomycin, VEGF inhibitors), atypical/typical HUS, TTP (check ADAMTS13), DIC, sepsis-related capillary leak, and tumor-related microangiopathy. The cycle timing and hemolysis labs anchor the diagnosis.
Monitoring
- CBC/platelets and peripheral smear for schistocytes each cycle
- LDH, haptoglobin and bilirubin (hemolysis screen)
- Creatinine/eGFR each cycle
- Daily weight, blood pressure, albumin and edema assessment (CLS surveillance)
Key trials & series
- Pivotal phase 3 in relapsed/refractory HCL (Kreitman, Leukemia 2018) — established reversible HUS (~7.5%) and CLS (~5%)
- Phase 1 pediatric ALL study (Wayne, Blood 2017) — dose-dependent CLS and HUS/TMA
Clinical pearls
- Anchor monitoring to hemolysis labs plus creatinine (HUS) and weight/BP/albumin (HUS vs CLS).
- Hydration is the key prevention; do not initiate if CrCl <30 mL/min.
- Do not retreat after HUS — anamnestic HUS classically appears at cycles 2-3.
- Most hairy-cell-leukemia events are reversible, but fatal CLS exists — escalate early.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Thrombotic MicroangiopathyPrerenal / Hemodynamic AKI
Evidence
7 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkMoxetumomab pasudotox in relapsed/refractory hairy cell leukemia.Kreitman RJ et al. · Leukemia 2018 · PMID 30030507Pivotal phase 3 trial establishing reversible HUS (~7.5%) and CLS (~5%).PMIDBL22 and lymphoid malignancies.Kreitman RJ et al. · Best Pract Res Clin Haematol 2006 · PMID 16997177Seminal anti-CD22 PE38 immunotoxin mechanism (predecessor BL22) and first dose-limiting HUS report.PMIDMoxetumomab pasudotox for hairy cell leukemia: preclinical development to FDA approval.Lin AY et al. · Blood Adv 2019 · PMID 31594764Reviews the anti-CD22 Fv-PE38 construct and frames CLS/HUS as the unique toxicities.PMIDCollateral Damages by Magic Bullets: Hemolytic Uremic and Capillary Leak Syndromes After Moxetumomab Pasudotox Therapy.Lien YH et al. · Am J Med 2019 · PMID 31233704Nephrology case of concurrent HUS and CLS with dialysis/steroid management.PMIDFatal capillary leak syndrome in a child with acute lymphoblastic leukemia treated with moxetumomab pasudotox for pre-transplant minimal residual disease reduction.Shah NN et al. · Pediatr Blood Cancer 2020 · PMID 32959985Documents that CLS can be fatal — underscores the boxed warning.PMIDPhase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia.Wayne AS et al. · Blood 2017 · PMID 28983018Dose-dependent CLS and HUS/TMA; dexamethasone prophylaxis reduced dose-limiting CLS.PMIDAnticancer Drug-Induced Acute Kidney Injury.Izzedine H et al. · Kidney Int Rep 2017 · PMID 29318217Onconephrology review of drug-induced TMA — risk factors and prevention.
Related agents
Other agents sharing the same signature kidney injury.