- AutoSCT: pt’s own cryopreserved HSCs rescue from myeloablative chemo
- Target: ≥2×10⁶ CD34+/kg min; ≥5×10⁶/kg optimal
- Pretransplant: EKG, LVEF, PFTs, Cr clearance, infectious screening, caregiver
- Melphalan 140 mg/m² standard (MM); regimens vary by disease
- G-CSF ± chemo; plerixafor for poor mobilizers
- Early: mucositis, infection, pancytopenia; late: 2°malignancy, cataract
- Cure rates: MM 20-30%, R/R NHL 40-60%, R/R HL 40-60%
- Maintenance (lenalidomide, ixazomib, rituximab) improves PFS post-autoSCT
Overview
- Concept: Patient’s own HSCs + cryopreservation (DMSO) → myeloablative chemo → stem cell rescue
- Mobilize HSCs → cryopreserve (storage ≥10 yrs) → HD chemo → infuse cells w/ brief rest
- Rescue mitigates prolonged neutropenia & severe hematologic toxicity
- No GVHD risk (autologous cells); no long-term IS needed
Pretransplant Testing
- Cardiac: EKG, LVEF (echo/MUGA)
- Pulmonary: PFTs, CXR, baseline O₂
- Renal: Cr clearance ≥40 mL/min/1.73m² preferred (≥200 mL/min acceptable)
- Hepatic: AST, ALT, bili
- Infectious: CMV, EBV, HSV, HIV, HBV, HCV, TB screening
- BM biopsy: disease burden & cellularity (selected)
- Caregiver: committed support essential during workup
Mobilization & Collection
- Target: ≥2×10⁶ CD34+/kg min (note: ~2×10⁶ lost in preservation/thaw)
- Optimal: ≥5×10⁶ CD34+/kg → aim higher for potential boost later
- No major difference in engraftment @ 2 vs 4 vs 6×10⁶/kg infused
- Standard G-CSF: 10 μg/kg daily × 4-5 days pre-collection
- Poor mobilizers (inadequate CD34+):
- Chemomobilization: high-dose CyPh or etoposide ± G-CSF
- Plerixafor + G-CSF rescue for non-responders
- Collection: apheresis catheter (most pts) or large-bore PIVs if adequate vasculature
- Preservation: DMSO (standard) or liquid nitrogen; fresh infusion = faster engraftment
High-Dose Chemotherapy Regimens
Preparative Regimens by Indication
| MM |
Newly dx |
Melphalan 140 mg/m² |
Can escalate to 200 mg/m² if tolerated |
|
R/R |
Melphalan |
2 cycles alkylating agents |
| AL amyloid |
Newly dx |
Melphalan |
Reduce intensity if age >70 |
|
R/R |
Melphalan ± thiotepa/bendamustine/CyPh |
Dose escalation |
| POEMS |
— |
Melphalan |
Thiotepa causes skin toxicity; daily showers × 48h |
| DLBCL/NHL |
R/R |
BEAM |
— |
| Primary CNS lymphoma |
Rituximab-naive/R |
TBI/CyPh/etoposide |
2-3 cycles |
| Germ cell tumor |
R/R |
Carboplatin/etoposide |
— |
| Systemic sclerosis |
R/R |
TBI/CyPh/etoposide + ATG |
— |
- Goal: myeloablative → eradicate disease
- Renal impairment (Cr clearance ≥200 mL/min): use melphalan 140 mg/m²
- Dose escalation (MM/AL amyloid): no RCT data; intensity trade-offs debated
- Timing: collections weeks post-diagnosis; rest 2-3 wks before infusion
Early Toxicities (1-4 wks post-infusion)
- Common (all pts): mucositis, N/V, anorexia, fatigue, pancytopenia
- Support: G-CSF, transfusions, broad-spectrum abx (ceftazidime)
- Graft failure: <1% (may require stem cell boost)
- Infection during neutropenia: high risk; fever workup mandatory
- Engraftment syndrome: fever + diarrhea, rash, weight gain
- Less common: pulmonary edema, renal/hepatic dysfunction
- Signals recovery but requires monitoring
Late Toxicities (months-years post-autoSCT)
- Immunosuppression: impaired reconstitution × many months-years
- Viral infections: CMV reactivation, others → significant morbidity/mortality
- Vaccination critical (robust response takes years)
- 2° malignancy: ↑3-7× vs general population (lower than allogeneic HCT)
- Immune recovery: 2-3 months partial; years for complete recovery
- Newly dx MM faster recovery than R/R disease
Maintenance & Tandem Strategies
- Single autoSCT + maintenance:
- FORTE trial: KRd maintenance → PFS 67.5 vs 46.2 mo (no OS diff @ 3y)
- Proteasome inhibitor ± IMiD maintenance improves PFS/OS
- Tandem autoSCT (2 transplants <6 mo): rarely superior to single + maintenance
- IFM95-04: tandem benefit (older data)
- STAMINA: tandem + consolidation vs tandem alone → no PFS/OS diff; ↑toxicity
- Reserve tandem for ultra-high-risk MM; toxicity often prohibitive
- Current standard: single autoSCT → lenalidomide/ixazomib/rituximab maintenance
Multiple Myeloma
- Most common autoSCT indication; cures ~20-30% newly diagnosed
- Timing: transplant after 4-6 cycles induction (≥PR)
- Rest 2-3 wks before HD chemo to maximize HSC yield, ↓apoptosis
- Optimal timing debated w/ modern induction (bortezomib/ixazomib)
- Regimen: melphalan 140 mg/m² (dose intensity not RCT-validated)
- Maintenance:
- KRd (carfilzomib/lenalidomide/dex) → PFS benefit
- Single agent (lenalidomide/ixazomib/rituximab) also effective
- Proteasome inhibitor preferred over IMiD monotherapy
Diffuse Large B-Cell Lymphoma (DLBCL)
- ~2/3 cured w/ standard chemo ± RT
- R/R chemosensitive: autoSCT salvage standard
- Salvage chemo: CHOP or rituximab-containing (pre-autoSCT)
- CORAL trial: autoSCT (ritual or non-ritual) → 2y EFS/OS 46%/55% vs 12%/32% (chemo alone)
- Regimen: BEAM conditioning standard; rituximab addition improves outcomes
- Cure rates: 40-50% R/R chemosensitive disease
Light Chain Amyloidosis (AL)
- Indications: age <70, cardiac stage I/II, adequate organ function
- Induction: bortezomib-based (CyBord preferred) × 4-6 cycles
- Target: CR before autoSCT
- Regimen: melphalan 140 mg/m² (reduced intensity if age >70)
- Alternative: dose escalation w/ thiotepa, bendamustine if R/R
- Outcomes: 2y OS >80%; CR rates improve w/ induction→autoSCT
- Special note: early organ involvement (cardiac, renal) worsens prognosis
POEMS Syndrome
- Rare autoSCT indication; case series benefit
- Regimen: melphalan ± thiotepa (skin toxicity w/ thiotepa)
- Daily showers × 48h post-thiotepa to reduce toxicity
- Limited data vs standard therapy
Follicular Lymphoma (FL)
- Indications: early progression (<2y from initial therapy)
- Indolent but incurable w/o intervention
- AutoSCT benefit in selected early relapse
- Outcomes: autoSCT 5y OS ~72% vs allogeneic ~69% (similar, ↓NRM w/ auto)
- Allogeneic only if R/R post-autoSCT (↑NRM w/ myeloablative)
- Transformation to DLBCL: ~3% per year (requires HD salvage therapy)
- Rituximab maintenance: extends remission duration post-autoSCT
Primary CNS Lymphoma
- Candidates: young, fit, ≥PR to induction chemo
- Consolidation: HD chemoradiation → autoSCT
- Regimen: TBI/CyPh/etoposide preferred over BEAM; thiotepa alternative
- Limited RCT data; registry studies suggest benefit
- Outcomes: variable (small series); consider clinical trials
Hodgkin Lymphoma (HL)
- Frontline: high cure rates w/ standard therapy
- R/R HL: autoSCT first-line salvage
- Chemotherapy-sensitive: 40-60% cure rates
- Chemo-refractory: 25-40% cure rates
- Maintenance (post-autoSCT): brentuximab vedotin ± nivolumab under investigation
- BV alone: ↑PFS, but neuropathy risk
- Nivolumab: rare ARDS signal
- No OS benefit shown yet; role evolving w/ frontline BV use
- Regimen: BEAM or TBI-based conditioning
Mantle Cell Lymphoma (MCL)
- Aggressive course except low IPI/Ki-67 subset (indolent)
- Frontline: intensive chemo (hyper-CVAD) → autoSCT consolidation (younger pts)
- Target: CR before autoSCT
- R/R: salvage → autoSCT if chemo-sensitive
- Regimen: BEAM or TBI-based conditioning
- Maintenance: rituximab ± targeted therapy (study-dependent)
Autoimmune Diseases
- Indications: MS, systemic sclerosis, RA, JIA, SLE, dermatomyositis, Crohn’s, autoimmune cytopenia
- Hypothesis: immunoablation + T cell reprogramming
- Systemic sclerosis (RCT data):
- AutoSCT vs monthly CyPh: 72m EFS 74% vs 47%; OS 80% vs 28%
- Subset w/ aggressive/progressive disease benefit most
- Other diseases: case series/small RCTs; clinical trials preferred
- CAR-T cell therapy: alternative strategy under investigation
Germ Cell Tumors (GCT)
- Relapsed/refractory disease: salvage autoSCT standard
- Regimen: 2-3 cycles high-dose carboplatin/etoposide
- Can use tandem autoSCT (within 6 mo) for ultra-high-risk
- Outcomes: 20-60% cure (Indiana series: 51% alive/PF @ 10y w/ tandem)
- Patient selection: chemotherapy-sensitive, adequate organ function
Pediatric Solid Tumors
- Chemosensitive tumors: dose intensification w/ autoSCT
- Indications: high-risk neuroblastoma (age >1y, metastatic, MYCN+), RMS, Ewing sarcoma
- High-risk: pelvic site, metastases, unfavorable histology
- Strategy: induction → autoSCT consolidation if chemo-responsive
- Outcomes: variable; early consolidation may improve EFS in selected pts
- MM: Melphalan 140 mg/m²; plerixafor for poor mobilizers; CD34+ ≥2×10⁶/kg min, ≥5×10⁶/kg optimal
- Tandem autoSCT: rarely superior vs single + maintenance; reserve for ultra-high-risk MM only
- Maintenance post-autoSCT: KRd (carfilzomib/lenalidomide/dex) most effective for PFS in MM; PI or IMiD also effective
- No GVHD (auto cells); no long-term IS required vs allogeneic
- Immune recovery: 2-3 mo partial; years complete; vaccination critical
References
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