📋 Key Information Summary
- Haematopoietic stem cell transplantation (HSCT) uses allogeneic (donor) or autologous (self) stem cells to restore haematopoiesis following myeloablative or reduced-intensity conditioning for haematological malignancies and selected non-malignant diseases.
- Australia performs approximately 1,000–1,200 HSCT procedures annually across 22 specialised transplant centres, with the majority in NSW, VIC, and QLD.
- Autologous HSCT is most commonly used for multiple myeloma, lymphoma (Hodgkin and non-Hodgkin), and selected germ cell tumours, serving as a high-dose chemotherapy rescue.
- Allogeneic HSCT is indicated for acute leukaemia (AML, ALL), high-risk MDS, CML (tyrosine kinase inhibitor failure), severe aplastic anaemia, and haemoglobinopathies including thalassaemia major.
- HLA matching is critical for allogeneic transplants — an 8/8 or 10/10 matched related donor is preferred; unrelated donors are sourced through the Australian Bone Marrow Donor Registry (ABMDR) or international registries.
- Conditioning regimens range from myeloablative (busulphan/cyclophosphamide, TBI-based) to reduced-intensity conditioning (fludarabine-based) depending on patient age, comorbidities, and disease risk.
- Graft-versus-host disease (GVHD) remains the leading cause of non-relapse morbidity and mortality in allogeneic HSCT, occurring in 30–50% of recipients (acute) and 30–70% (chronic).
- Acute GVHD prophylaxis standard is ciclosporin + short-course methotrexate; first-line treatment is methylprednisolone 2 mg/kg/day with calcineurin inhibitor optimisation.
- Major complications include infections (bacterial, viral reactivation — CMV, EBV, adenovirus; fungal — Aspergillus, Candida), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and graft failure.
- Autologous HSCT carries lower transplant-related mortality (TRM) of 1–3% compared to allogeneic HSCT (TRM 10–30% depending on conditioning intensity and donor source).
- Survival outcomes vary: autologous HSCT for myeloma 5-year OS 50–60%; allogeneic HSCR for AML in CR1 5-year OS 50–70% (matched sibling), 40–60% (matched unrelated).
- Long-term follow-up is essential for monitoring late effects including secondary malignancies, endocrine dysfunction, cataracts, avascular necrosis, and chronic GVHD.
- Aboriginal and Torres Strait Islander patients face significant barriers to HSCT access including geographic remoteness, donor registry underrepresentation, and systemic healthcare inequities requiring targeted programmes.
Introduction & Australian Epidemiology
Haematopoietic stem cell transplantation (HSCT) is a critical therapeutic modality in which haematopoietic stem cells — sourced from bone marrow, peripheral blood, or umbilical cord blood — are infused to restore normal haematopoiesis following intensive conditioning therapy. It is employed for a range of malignant haematological disorders, selected solid tumours, bone marrow failure syndromes, haemoglobinopathies, and severe immunodeficiencies.
The procedure encompasses two broad categories: autologous HSCT, in which the patient's own previously harvested stem cells are reinfused after high-dose chemotherapy, and allogeneic HSCT, in which stem cells from a human leucocyte antigen (HLA)-matched or haploidentical donor are used to establish a new donor-derived haematopoietic and immune system.
| Parameter | Australia |
|---|---|
| Annual HSCT procedures | ~1,000–1,200 (autologous ~60%, allogeneic ~40%) |
| Transplant centres | 22 accredited centres across all states/territories |
| ABMDR registered donors | ~800,000 volunteer donors |
| Primary indications (autologous) | Multiple myeloma (~50%), lymphoma (~40%), other (~10%) |
| Primary indications (allogeneic) | AML (~35%), ALL (~20%), MDS (~15%), CML, SAA, other (~30%) |
| Median age at transplant | Autologous 60 years; Allogeneic 48 years |
| 100-day TRM (autologous) | 1–3% |
| 100-day TRM (allogeneic, MUD) | 10–20% |
| Governing body | Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) |
The Australasian Bone Marrow Transplant Recipient Registry (ABMTRR), administered by the Australasian Leukaemia and Lymphoma Group (ALLG), collects data on all HSCT procedures in Australia and New Zealand, providing essential outcome data and quality assurance. Australian transplant outcomes are comparable to international benchmarks, with the National Health and Medical Research Council (NHMRC) and the Blood Service providing national oversight of donor recruitment and cord blood banking.
PBS and MBS relevance: HSCT procedures are funded through state/territory health departments via specialised transplant centres. PBS-listed conditioning agents (busulphan, cyclophosphamide, fludarabine, melphalan, thiotepa) and supportive care medications (G-CSF, antifungals, antivirals) are available as general or authority benefits. MBS items cover associated inpatient stays and outpatient consultations.
Types: Allogeneic vs Autologous
Autologous HSCT
Autologous transplantation involves harvesting the patient's own peripheral blood stem cells (PBSCs) after mobilisation with granulocyte colony-stimulating factor (G-CSF) ± plerixafor, followed by reinfusion after high-dose myeloablative chemotherapy. The primary mechanism is dose escalation of cytotoxic therapy rather than immunological graft-versus-tumour effect.
Key Feature
No Donor Required
Self-derived stem cells eliminate HLA matching, GVHD risk, and donor availability constraints.
Setting: Outpatient mobilisation → inpatient transplant (2–3 weeks)
Limitation
No Graft-vs-Tumour Effect
Relies solely on dose-intensified chemotherapy; no immunological anti-malignancy benefit.
Limitation: Higher relapse rates in some diseases vs allogeneic
Advantage
Low TRM
100-day transplant-related mortality 1–3%; 5-year NRM <5% in most series.
Setting: Suitable for older patients and those with comorbidities
Autologous HSCT — Stem Cell Collection
- Mobilisation: G-CSF (filgrastim) 10 µg/kg/day SC for 4–5 days; plerixafor (Mozobil®) 0.24 mg/kg SC added for poor mobilisers (PBS Authority Required)
- Collection: Leukapheresis via central venous catheter; target CD34+ cell dose ≥2 × 10⁶/kg (ideally ≥3–5 × 10⁶/kg)
- Cryopreservation: Dimethyl sulphoxide (DMSO) at −80°C or liquid nitrogen storage
- Reinfusion: Thawed at bedside, infused IV over 15–30 minutes; toxicity includes DMSO-related nausea, bradycardia, and rarely anaphylaxis
Allogeneic HSCT
Allogeneic transplantation uses haematopoietic stem cells from an HLA-matched or haploidentical donor, providing both a new haematopoietic system and a donor-derived immune system capable of exerting a graft-versus-tumour (GvT) effect. This immunological benefit is critical for sustained remission in diseases such as AML, ALL, CML, and MDS.
Matched Sibling
Gold Standard Donor
8/8 or 10/10 HLA-matched sibling donor; TRM 10–15%, lowest GVHD rates.
Available: ~30% of patients have an HLA-matched sibling
Matched Unrelated
ABMDR / International Registry
10/10 HLA-matched unrelated donor; TRM 15–20%; search time 2–4 months.
Setting: ABMDR + international networks (WMDA, Be The Match)
Haploidentical
Post-Transplant Cyclophosphamide
5/10 or 6/10 HLA-matched family donor; PT-Cy protocol reduces GVHD to comparable rates with MUD.
Setting: Rapidly expanding use; >90% patients find a donor
Stem Cell Sources
| Source | Advantages | Disadvantages | Australian Use |
|---|---|---|---|
| Peripheral blood (PBSC) | Faster engraftment; easier collection | Higher chronic GVHD risk | ~80% of allogeneic transplants |
| Bone marrow | Lower chronic GVHD; better in paediatric recipients | General anaesthesia; slower engraftment | ~15% of allogeneic transplants |
| Cord blood | Less strict HLA matching; rapid availability | Limited cell dose; slow engraftment; higher graft failure | ~5% of allogeneic transplants |
Filgrastim (G-CSF)
Neupogen® · Zarzio® · Granulocyte colony-stimulating factor
Mobilisation dose
10 µg/kg/day SC for 4–5 days
Engraftment dose
5 µg/kg/day SC from Day +5 until ANC >0.5 × 10⁹/L for 3 days
Renal adjustment
Not required
PBS status
✔ PBS General Benefit
Plerixafor
Mozobil® · CXCR4 antagonist
Dose
0.24 mg/kg SC, 11 hours prior to apheresis
Indication
Poor mobilisers; used with G-CSF
Renal adjustment
Reduce to 0.16 mg/kg if CrCl <50 mL/min
PBS status
⚠ PBS Authority Required
Conditioning Regimens & HLA Matching
Conditioning Regimens
Conditioning therapy is administered in the days immediately preceding stem cell infusion to eradicate residual malignant cells, create immunological space for donor engraftment, and provide adequate immunosuppression to prevent graft rejection. The intensity of conditioning is tailored to the patient's age, performance status, comorbidities (assessed by the HCT-Comorbidity Index), disease type, and donor source.
Myeloablative Conditioning (MAC)
Full-intensity regimens that result in irreversible pancytopenia; stem cell rescue is obligatory. Suitable for younger patients (<55–60 years) with good performance status.
Busulphan + Cyclophosphamide (Bu/Cy)
Busulphan oral/IV (Busilvex®) + Cyclophosphamide · Myeloablative
Busulphan
IV 3.2 mg/kg/day (0.8 mg/kg q6h) × 4 days (Days −7 to −4) OR oral 1 mg/kg q6h × 4 days
Cyclophosphamide
60 mg/kg/day IV × 2 days (Days −3 to −2)
Busulphan TDM
Therapeutic drug monitoring recommended; target AUC 900–1500 µmol·min/L per dose
PBS status
✔ PBS General Benefit
TBI + Cyclophosphamide
Total body irradiation + Cyclophosphamide · Myeloablative
TBI
12 Gy in 6 fractions over 3 days (Days −7 to −5) or 13.2 Gy in 8 fractions
Cyclophosphamide
60 mg/kg/day IV × 2 days (Days −3 to −2)
Indications
ALL (preferred), some AML subtypes; requires radiation oncology referral
PBS status
✔ PBS General Benefit
Reduced-Intensity Conditioning (RIC)
Non-myeloablative or reduced-intensity regimens that produce minimal cytopenia and rely predominantly on the graft-versus-tumour effect for disease control. Suitable for older patients (>55–60 years), those with comorbidities, or when the disease is highly immunosensitive.
Fludarabine + Busulphan (Reduced)
Fludara® + Busilvex® · RIC regimen
Fludarabine
30 mg/m²/day IV × 5 days (Days −6 to −2)
Busulphan
IV 3.2 mg/kg/day × 2 days (Days −3 to −2) — reduced intensity
PBS status
✔ PBS General Benefit
Fludarabine + Melphalan
Fludara® + Alkeran® · RIC regimen
Fludarabine
25 mg/m²/day IV × 5 days (Days −5 to −1)
Melphalan
140 mg/m² IV × 1 day (Day −1)
PBS status
✔ PBS General Benefit
Autologous HSCT Conditioning
Melphalan (High-dose)
Alkeran® · Standard myeloma conditioning
Dose
200 mg/m² IV × 1 day (Day −1); reduced to 140 mg/m² if CrCl <60 mL/min or age >65
Indication
Multiple myeloma (standard of care)
PBS status
✔ PBS General Benefit
BEAM (Carmustine/Etoposide/Ara-C/Melphalan)
Lymphoma conditioning regimen
Regimen
BCNU 300 mg/m² (Day −7), Etoposide 100–200 mg/m² BID × 4d (Days −6 to −3), Ara-C 200 mg/m² BID × 4d, Melphalan 140 mg/m² (Day −1)
Indication
Relapsed/refractory Hodgkin and non-Hodgkin lymphoma
PBS status
✔ PBS General Benefit
Busulphan therapeutic drug monitoring (TDM): IV busulphan AUC monitoring is strongly recommended to optimise efficacy and minimise toxicity (VOD/SOS, seizures). Target first-dose AUC 900–1500 µmol·min/L. Available at major transplant centres with rapid turnaround (24–48 hours). Phenobarbitone 1 mg/kg IV/PO is used as seizure prophylaxis during busulphan administration.
HLA Matching
HLA matching at high resolution (allele-level) for HLA-A, -B, -C, -DRB1, and -DQB1 loci (10/10 match) is the standard for allogeneic HSCT. Mismatch at even a single locus increases the risk of GVHD, graft failure, and transplant-related mortality.
| Match Level | HLA Loci | GVHD Risk | Recommendation |
|---|---|---|---|
| 10/10 Matched | A, B, C, DRB1, DQB1 | Lowest | Preferred donor source |
| 9/10 Matched | Single mismatch | Moderate increase | Acceptable; consider haploidentical alternative |
| 8/8 Matched | A, B, C, DRB1 (4-locus) | Acceptable | Minimum acceptable for unrelated donor |
| Haploidentical | 5/10 or 6/10 | Higher (mitigated by PT-Cy) | Post-transplant Cy protocol; rapidly expanding |
The Australian Bone Marrow Donor Registry (ABMDR) coordinates national donor searches and partners with the World Marrow Donor Association (WMDA) to access >39 million registered donors internationally. For patients lacking a matched sibling or unrelated donor, haploidentical family donors using post-transplant cyclophosphamide (PT-Cy) protocols have expanded donor availability to >90% of patients.
Graft-versus-Host Disease (GVHD)
GVHD is the principal immunological complication of allogeneic HSCT, occurring when donor T lymphocytes recognise host tissues as foreign and mount an immune-mediated attack. It is classified as acute (typically within 100 days of transplant) or chronic (>100 days), though temporal definitions have been revised by the NIH Consensus Criteria to focus on clinical manifestations rather than arbitrary time points.
Acute GVHD
Acute GVHD affects 30–50% of allogeneic HSCT recipients and involves three target organs: skin, liver, and gastrointestinal tract. It results from donor T-cell activation by host antigen-presenting cells, amplified by cytokine storm (TNF-α, IL-1, IL-6).
Grading (Modified Glucksberg / IBMTR Severity Index)
| Grade | Skin (% BSA) | Liver (Bilirubin) | GI (mL/day diarrhoea) | Functional Impairment |
|---|---|---|---|---|
| I (Mild) | Stage 1 (<25%) | — | — | Minimal |
| II (Moderate) | Stage 1–2 | Stage 1 | Stage 1 | Mild |
| III (Severe) | Stage 2–3 | Stage 2–3 | Stage 2–3 | Marked |
| IV (Life-threatening) | Stage 4 (bullae) | Stage 4 | Stage 4 (severe pain/ileus) | Extreme |
Acute GVHD Prophylaxis
Ciclosporin + Methotrexate
Neoral® / Sandimmun® + Methotrexate · Standard prophylaxis
Ciclosporin
3 mg/kg/day IV from Day −1, switch to PO when tolerating; target trough 200–350 ng/mL
Methotrexate
15 mg/m² IV Day +1; 10 mg/m² IV Days +3, +6, +11
Monitoring
Ciclosporin trough levels twice weekly; renal function, Mg²⁺, K⁺
PBS status
✔ PBS General Benefit
Tacrolimus + Methotrexate
Prograf® · Alternative calcineurin inhibitor
Tacrolimus
0.03 mg/kg/day IV continuous infusion from Day −2; target trough 10–15 ng/mL early post-transplant
PBS status
✔ PBS General Benefit
Post-transplant cyclophosphamide (PT-Cy) protocol: For haploidentical and some mismatched transplants, cyclophosphamide 50 mg/kg/day IV on Days +3 and +4, combined with tacrolimus and mycophenolate mofetil from Day +5. This has dramatically improved outcomes for haploidentical HSCT, making it comparable to MUD transplants.
Acute GVHD Treatment
- First-line: Methylprednisolone 2 mg/kg/day IV (or prednisolone 2 mg/kg/day PO) for 7–14 days, then taper over 8–12 weeks if responding
- Steroid-refractory acute GVHD (progression after 3–5 days or no improvement after 7 days):
- Ruxolitinib (Jakavi®) 10 mg PO BD — PBS Authority Required for steroid-refractory acute GVHD; FDA/EMA approved; emerging standard second-line in Australia
- Extracorporeal photopheresis (ECP) — available at select Australian centres
- Infliximab, mycophenolate mofetil, ATG — variable evidence
- GI GVHD with severe diarrhoea (>500 mL/day): Upper and lower GI biopsies for confirmation; budesonide 9 mg/day PO as adjunct; IV fluid and electrolyte replacement
Ruxolitinib
Jakavi® · JAK1/JAK2 inhibitor
Indication
Steroid-refractory acute GVHD (≥12 years)
Dose
10 mg PO BD; reduce to 5 mg BD if platelets <20 × 10⁹/L
Key toxicity
Cytopenias (thrombocytopenia, anaemia), infections (CMV reactivation)
PBS status
⚠ PBS Authority Required
Methylprednisolone
Solu-Medrol® · Corticosteroid
Dose
2 mg/kg/day IV in divided doses; taper over 8–12 weeks if responding
Response rate
~50–70% initial response; ~35% complete response
PBS status
✔ PBS General Benefit
Chronic GVHD
Chronic GVHD occurs in 30–70% of allogeneic HSCT recipients surviving >100 days and is the leading cause of late non-relapse mortality. It resembles autoimmune disorders with multi-organ fibrosis, lichenoid changes, and sclerosis.
NIH Consensus Criteria — Severity Scoring
Mild
Score 1–2 organs
Mild skin (maculopapular rash <20% BSA), mild oral, mild hepatic, no significant functional impairment.
Setting: Topical therapy; outpatient management
Moderate
Score 3–4 organs or moderate single organ
Moderate skin (20–50% BSA), moderate GI (diarrhoea 500–1500 mL/day), moderate liver (bilirubin 34–102 µmol/L).
Setting: Systemic immunosuppression required
Severe
Score ≥5 organs or major functional impairment
Severe sclerotic skin, bronchiolitis obliterans, fascial involvement, severe oesophageal/GI disease.
Setting: Aggressive systemic therapy; specialist referral
Chronic GVHD Treatment
- First-line: Prednisolone 0.5–1 mg/kg/day PO ± calcineurin inhibitor (ciclosporin or tacrolimus); taper over 12–24 months
- Second-line (steroid-refractory/intolerant): Ruxolitinib (Jakavi®) — now PBS-listed for chronic GVHD; extracorporeal photopheresis; mycophenolate mofetil; sirolimus
- Skin-limited: Topical corticosteroids, tacrolimus ointment; narrow-band UVB phototherapy
- Oral: Dexamethasone elixir 0.5 mg/5 mL swish-and-spit; ciclosporin oral solution; topical tacrolimus
- Bronchiolitis obliterans: Azithromycin 250 mg PO three times weekly (anti-inflammatory dose); montelukast; augmented immunosuppression
- Ocular (sicca syndrome): Artificial tears, ciclosporin 0.05% eye drops, punctal plugs
Infection risk with GVHD immunosuppression: All patients on systemic immunosuppression require Pneumocystis jirovecii prophylaxis (co-trimoxazole 480 mg PO daily or 960 mg 3 times/week), antiviral prophylaxis (aciclovir 400 mg PO BD for HSV/VZV), and antifungal prophylaxis (fluconazole or posaconazole). Monitor for CMV reactivation with quantitative PCR weekly during the first 100 days.
Indications, Complications & Outcomes
Indications for HSCT
Autologous HSCT — Approved Indications
| Disease | Setting | Evidence Level |
|---|---|---|
| Multiple myeloma | First-line after induction (age ≤70, fit) | Standard of care (IFM, MRC trials) |
| Multiple myeloma (tandem) | High-risk disease; selected patients | Controversial; centre-dependent |
| Relapsed Hodgkin lymphoma | Chemosensitive relapse after salvage | Standard of care (BNCI/CORAL) |
| Relapsed DLBCL | Chemosensitive relapse; IPI-adjusted | Standard of care (PARMA trial) |
| Relapsed germ cell tumour | First or subsequent relapse; IGCCCG intermediate/poor | Category 1 (TIGER trial) |
| Systemic AL amyloidosis | Selected patients with cardiac stage I–II | Centre-dependent; requires specialist assessment |
Allogeneic HSCT — Approved Indications
| Disease | Setting | Recommended Donor |
|---|---|---|
| AML — high risk (ELN 2022) | CR1 with adverse risk genetics (FLT3-ITD, TP53, complex karyotype) | MSD > MUD > Haplo |
| AML — standard risk | CR2 or beyond | Any matched donor |
| ALL — high risk (Ph+, Ph-like) | CR1 (MRD positive) or CR2 | MSD > MUD |
| MDS — higher risk | IPSS-R intermediate-2/high; excess blasts | Any matched donor; RIC for older patients |
| CML | TKI failure or resistance; T315I mutation | Any matched donor |
| Severe aplastic anaemia | Immunosuppressive therapy failure; first-line if MSD available and age <50 | MSD preferred; MUD if no MSD |
| Thalassaemia major | Class I–II Pesaro; MSD available | MSD only |
| Sickle cell disease | Severe complications (stroke, ACS, VOC); MSD available | MSD; haploidentical expanding |
| Inherited immunodeficiencies | SCID, WAS, CGD, HLH | MSD > MUD > Haplo |
Complications
Infections
Infections are the leading cause of morbidity and mortality post-HSCT, with risk stratified by the phase of immune reconstitution:
Pre-engraftment (Day 0 to +30)
Neutropenic infections: Gram-negative bacteraemia (Pseudomonas, E. coli), Gram-positive (coagulase-negative staphylococci, viridans streptococci), Candida spp. Empirical: piperacillin-tazobactam 4.5 g IV q8h or meropenem 1 g IV q8h. Antifungal: fluconazole 400 mg daily or posaconazole 300 mg daily (PBS Authority).
Early post-engraftment (Day +30 to +100)
T-cell dysfunction: CMV reactivation (monitor qPCR weekly; treat with ganciclovir 5 mg/kg IV BD or valganciclovir 900 mg PO BD), adenovirus, BK virus (haemorrhagic cystitis), Aspergillus spp. Continue antifungal prophylaxis (posaconazole or voriconazole).
Late post-engraftment (>Day +100)
B-cell dysfunction: Encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae); Pneumocystis jirovecii; VZV reactivation. Ensure pneumococcal vaccination from +6 months; continue PJP and antiviral prophylaxis for 12+ months or while on immunosuppression.
Veno-Occlusive Disease / Sinusoidal Obstruction Syndrome (VOD/SOS)
VOD/SOS — medical emergency: Incidence 5–15% (myeloablative conditioning); up to 40% with prior gemtuzumab ozogamicin. Presents with painful hepatomegaly, weight gain, jaundice, and ascites within 21 days of conditioning. EBMT criteria for diagnosis: bilirubin ≥34 µmol/L + ≥2 of: painful hepatomegaly, weight gain >5%, ascites. Severe VOD/multi-organ dysfunction mortality >80% without treatment.
Defibrotide
Defitelio® · Oligonucleotide · Treatment of severe VOD/SOS
Dose
6.25 mg/kg IV q6h (25 mg/kg/day) for ≥21 days or until VOD resolution
Evidence
Phase III HOPE-BMT trial; TGA approved
Key precaution
Concurrent anticoagulation contraindicated; risk of haemorrhage
PBS status
✗ Not PBS listed
Other Major Complications
| Complication | Incidence | Prevention / Management |
|---|---|---|
| Graft failure / rejection | Primary 5%; secondary 2–5% | Ensure adequate cell dose; donor lymphocyte infusion (DLI) for secondary failure |
| Haemorrhagic cystitis | 10–30% (early: cyclophosphamide; late: BK virus) | Hyperhydration + MESNA; cidofovir for BK-associated HC |
| Thrombotic microangiopathy (TMA) | 5–15% | Withdraw calcineurin inhibitor; eculizumab in refractory cases |
| Post-transplant lymphoproliferative disorder (PTLD) | 1–5% (higher with T-cell depletion, ATG) | Rituximab pre-emptive therapy for EBV viraemia; reduce immunosuppression |
| Secondary malignancy | 5–15% at 10 years | Lifelong cancer screening; skin checks; cervical screening |
| Endocrine dysfunction | Gonadal failure 70–90%; hypothyroidism 10–30% | Hormone replacement; fertility counselling pre-transplant |
Outcomes
Transplant outcomes in Australia are tracked by the ABMTRR and benchmarked against international registries (CIBMTR, EBMT). Outcomes vary significantly by disease, conditioning intensity, donor source, patient age, and comorbidities.
| Disease / Transplant Type | 3-Year OS | Key Prognostic Factors |
|---|---|---|
| Autologous — Myeloma (1st ASCT) | 75–85% | ISS stage, CR after induction, cytogenetics |
| Autologous — Hodgkin lymphoma (2nd CR) | 60–70% | Chemosensitivity to salvage; PET-negative pre-ASCT |
| Autologous — DLBCL (2nd CR) | 50–60% | IPI, time to relapse, chemosensitivity |
| Allogeneic — AML CR1 (MSD, MAC) | 55–70% | ELN risk group, MRD status, age |
| Allogeneic — AML CR1 (MUD, RIC) | 45–60% | Comorbidities, disease status at transplant |
| Allogeneic — ALL CR1 (Ph+) | 50–65% | MRD status, TKI response, age |
| Allogeneic — MDS higher risk | 35–50% | IPSS-R, blast %, age, comorbidities |
| Allogeneic — SAA (MSD) | 75–90% | Age, prior IST, cell dose |
Special Populations
Pregnancy & Fertility
Pre-transplant counselling
All patients of reproductive age must receive fertility preservation counselling prior to conditioning. Referral to reproductive endocrinology: oocyte/embryo cryopreservation, sperm banking. GnRH agonist (goserelin/Zoladex® — PBS General Benefit) for ovarian suppression during chemotherapy may offer partial protection.
Post-transplant pregnancy
Pregnancy should be avoided for at least 12–24 months post-HSCT, and only after immunosuppression discontinued. Most autologous HSCT recipients recover fertility; allogeneic recipients have higher rates of gonadal failure (70–90%). Successful pregnancies reported but require specialist obstetric management.
Teratogenic risk
Mycophenolate mofetil (MMF) is Category D (teratogenic); must use reliable contraception during and for 6 weeks after cessation. Ciclosporin and tacrolimus are Category C; discuss risk–benefit.
Paediatric HSCT
Key indications
ALL (high risk/relapsed), AML, inherited bone marrow failure syndromes (Fanconi, DBA), haemoglobinopathies (thalassaemia major, SCD), severe combined immunodeficiency (SCID — emergency transplant), inherited metabolic disorders, HLH.
Donor selection
MSD preferred; MUD with ABMDR rapid search; haploidentical with PT-Cy increasingly used. Cord blood is used more frequently in paediatric recipients due to lower cell dose requirements and less stringent HLA matching.
Conditioning
Weight-based dosing essential for all conditioning agents. Busulphan TDM critical in infants (<1 year). Reduced-intensity conditioning used for non-malignant indications. TBI generally avoided in children <3 years due to neurocognitive and growth effects.
Late effects
Growth hormone deficiency, gonadal failure (require endocrine follow-up), secondary malignancy risk, cataracts, dental abnormalities. Transition to adult services must be planned.
Elderly Patients
Age consideration
No absolute age cutoff for allogeneic HSCT; physiological age and comorbidities (HCT-CI score) more important. RIC regimens have expanded eligibility to age 70–75 for selected patients. Autologous HSCT performed up to age 75 for myeloma with careful patient selection.
Assessment tools
HCT-Comorbidity Index (HCT-CI), geriatric assessment (frailty screening), cardiac function (echocardiogram, MUGA), pulmonary function (DLCO), hepatic/renal function.
Renal Impairment
Dose adjustments
Melphalan: reduce to 140 mg/m² if CrCl <60 mL/min. Busulphan: dose adjustment based on TDM. Methotrexate: omit Day +11 in setting of renal impairment or mucositis. Ciclosporin/tacrolimus: renal toxicity risk; requires close monitoring and dose reduction.
Nephrotoxic agents
Avoid concurrent aminoglycosides. Vancomycin trough-guided dosing. Amphotericin B deoxycholate contraindicated; use liposomal formulation (AmBisome® — PBS Authority).
Hepatic Impairment
Assessment
Liver function assessment essential pre-transplant. Hepatitis B surface antigen/antibody and hepatitis C antibody testing mandatory. If HBsAg positive, commence antiviral prophylaxis (entecavir 0.5 mg/day PO — PBS General Benefit) prior to conditioning and continue for 12–18 months post-transplant.
VOD risk
Pre-existing liver disease increases VOD/SOS risk. Consider defibrotide prophylaxis in high-risk patients. Avoid hepatotoxic drug combinations.
Immunocompromised
Pre-transplant infection screening
CMV IgG (donor and recipient), EBV IgG, HSV IgG, VZV IgG, HBV, HCV, HIV, HTLV, Toxoplasma IgG, Syphilis (RPR), TB (IGRA), Strongyloides serology (ATSI patients, tropical regions).
Vaccination programme
Revaccination schedule commencing +6 months post-HSCT: pneumococcal (PCV13 × 3 then PPSV23), Hib, DTPa, IPV, meningococcal, hepatitis B, influenza (from +3–6 months). Live vaccines contraindicated until +24 months and off immunosuppression.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander peoples experience significant disparities in access to and outcomes from haematopoietic stem cell transplantation in Australia. These inequities are driven by geographical remoteness, systemic barriers within the healthcare system, cultural safety concerns, and underrepresentation in donor registries.
Recommendations: All transplant centres should implement cultural safety frameworks as per the NHMRC Aboriginal and Torres Strait Islander Health guidelines. Telehealth-based post-transplant follow-up should be prioritised for remote patients. Haploidentical donor programmes should be expanded to address the donor availability gap for ATSI patients. Partnerships with Aboriginal Community Controlled Health Organisations (ACCHOs) for pre- and post-transplant care coordination.
📚 References
- 1. Australasian Leukaemia and Lymphoma Group (ALLG). Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) Annual Report 2023. Sydney: ALLG; 2023.
- 2. Niederwieser D, Baldomero H, Bazuaye N, et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in outcomes reported from a worldwide network. Blood. 2022;139(10):1433–1447.
- 3. D'Souza A, Fretham C, Lee SJ, et al. Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant. 2020;26(8):e177–e182.
- 4. Penack O, Marchetti M, Ruutu T, et al. Management of veno-occlusive disease/sinusoidal obstruction syndrome — revised European Society for Blood and Marrow Transplantation (EBMT) clinical practice guidelines. Bone Marrow Transplant. 2020;55:1–11.
- 5. Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800–1810.
- 6. Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021;385(3):228–238.
- 7. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295–304.
- 8. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–956.
- 9. Australian Bone Marrow Donor Registry (ABMDR). Donor recruitment and HLA matching guidelines. Sydney: ABMDR; 2024. Available from: abmdr.org.au.
- 10. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345–1377.
- 11. Snowden JA, Sánchez-Ortega I, Corbacioglu S, et al. Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022;57:1217–1239.
- 12. Battiwalla M, Tichelli A, Majhail NS. Long-term survivorship after hematopoietic cell transplantation: roadmap for follow-up. Biol Blood Marrow Transplant. 2020;26(3):e55–e65.
- 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).
- 14. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework. Canberra: AIHW; 2023.
- 15. Palliative Care Australia. National palliative care standards. 5th ed. Canberra: PCA; 2018. Referenced for end-of-life considerations in transplant setting.