What is HSCT?
Haematopoietic Stem Cell Transplant (HSCT) replaces a diseased or ablated haematopoietic system with healthy stem cells capable of reconstituting full blood cell production. It is the only curative option for many haematological malignancies and inherited marrow disorders.
Autologous HSCT (Auto-SCT)
Principle
Patient's own stem cells are collected, cryopreserved, then re-infused after high-dose chemotherapy (the patient is their own donor).
| Feature | Detail |
|---|
| GvHD risk | None — self cells |
| Immune suppression | Not required post-infusion |
| Collection | Peripheral blood after G-CSF mobilisation |
| Main indications | Multiple myeloma, Hodgkin lymphoma, Non-Hodgkin lymphoma, Germ cell tumours |
| Relapse risk | Higher — no graft-versus-tumour effect |
No GvHD
No GvT effect
Faster engraftment
Allogeneic HSCT (Allo-SCT)
Principle
Stem cells from a healthy donor (related or unrelated) replace the recipient's haematopoietic system — GvHD risk but also beneficial graft-versus-tumour (GvT) effect.
| Donor Type | Details |
|---|
| HLA-matched sibling | Ideal — 25% chance per full sibling; most common in GCC due to consanguinity |
| Matched Unrelated Donor (MUD) | Volunteer registry (WMDA); longer search time |
| Haploidentical | Half-matched (parent/child/sibling) — used when no full match; post-Cy protocol |
| Umbilical cord blood | HLA tolerance, limited cell dose, slower engraftment |
GvT effect — anti-tumour
GvHD risk
Immunosuppression needed
Conditioning Regimens
Myeloablative Conditioning (MAC)
High-dose chemotherapy ± Total Body Irradiation (TBI) — completely destroys recipient's marrow. Used in younger/fitter patients. Higher toxicity but lower relapse.
| Regimen | Drugs | Used For |
|---|
| BuCy | Busulfan + Cyclophosphamide | AML, MDS, thalassaemia |
| CyTBI | Cyclophosphamide + TBI 12 Gy | ALL, CML |
| BuFlu | Busulfan + Fludarabine | AML (modified MAC) |
Reduced Intensity Conditioning (RIC)
Lower-dose chemotherapy — relies more on GvT effect. Used in elderly, patients with comorbidities. Lower toxicity but higher relapse risk.
| Regimen | Drugs | Used For |
|---|
| Flu-Mel | Fludarabine + Melphalan | Most RIC allo-SCT |
| Flu-Bu (RIC) | Fludarabine + low-dose Busulfan | MDS, AML (elderly) |
| Flu-Cy-TBI | Fludarabine + Cy + low TBI 2 Gy | Non-myeloid malignancies |
Stem Cell Sources
| Source | Collection Method | Key Features |
|---|
| Peripheral blood | Apheresis after G-CSF mobilisation (4–5 days) | Most common; faster engraftment; higher cGvHD risk |
| Bone marrow | Harvest under general anaesthesia (posterior iliac crests) | Lower cGvHD risk; slower engraftment; donor GA risk |
| Cord blood | Collected at delivery, cryopreserved in bank | HLA mismatch tolerated; limited cell dose; very slow engraftment |
GCC Context
KFSH&RC Riyadh
King Faisal Specialist Hospital & Research Centre is one of the world's largest BMT centres — over 1,000 transplants/year.
- Saudi Arabia, UAE, Qatar have well-established BMT programmes
- Sickle cell disease and beta-thalassaemia are major indications in GCC Arab populations — allo-SCT offers cure
- High consanguinity rates in Arab families → increased sibling HLA-match probability
- National registries growing: Saudi Stem Cell Donor Registry
- Religious and family considerations relevant in consent process
KFSH Riyadh — world-leading BMT
Sickle cell / thalassaemia high-volume
Sibling match rates higher in GCC
Indications Summary
| Indication | Transplant Type | Notes |
|---|
| Multiple myeloma | Autologous | Standard of care after induction; melphalan 200 conditioning |
| Hodgkin lymphoma (relapsed/refractory) | Autologous | Salvage chemo then auto-SCT |
| Diffuse large B-cell lymphoma (relapsed) | Autologous (or allo) | Auto-SCT if chemo-sensitive relapse |
| AML | Allogeneic | Intermediate/high risk in CR1; auto possible low-risk |
| ALL | Allogeneic | High-risk or relapsed; CyTBI conditioning |
| MDS | Allogeneic | Potentially curative; RIC for older patients |
| Aplastic anaemia | Allogeneic | Sibling match preferred; CyATG conditioning |
| Sickle cell disease | Allogeneic | Curative — major GCC indication; sibling HLA-matched |
| Beta-thalassaemia | Allogeneic | Curative in children; Pesaro risk classification |
| Germ cell tumours | Autologous | High-dose salvage therapy |
Conditioning Phase Overview
Conditioning begins 7–10 days before stem cell infusion (Day 0). It serves two purposes: (1) ablate the recipient's diseased marrow to make space for donor cells, and (2) provide sufficient immunosuppression to prevent graft rejection.
Severe Mucositis Management
Priority Nursing Action
Mucositis is the most distressing acute complication of conditioning — affects up to 75% of allo-SCT patients.
- 1
Oral assessment every 2 hours (WHO oral mucositis scale)
- 2
Mouth care protocol: 0.9% NaCl rinse / chlorhexidine 0.12% alternating — every 2 hours while awake
- 3
Morphine PCA initiated for Grade 3–4 mucositis
- 4
Palifermin (KGF — keratinocyte growth factor) 60 mcg/kg/day x3 days pre-conditioning reduces Grade 3–4 mucositis
- 5
TPN initiated when oral/enteral intake <50% requirements
Grade 3–4: unable to eat/drink
PCA morphine required
Haemorrhagic Cystitis Prevention
Caused by acrolein (cyclophosphamide metabolite) — bladder epithelial toxicity. Presents as haematuria, dysuria, frequency. Can be severe with clots.
| Intervention | Protocol |
|---|
| Hyperhydration | 3 L/m²/day IV during and 24–48h after cyclophosphamide |
| Mesna (sodium 2-mercaptoethanesulfonate) | 60–100% of cyclophosphamide dose — given at 0, 4, 8h post-Cy (or continuous infusion) |
| Urinary output monitoring | Urine output ≥200 mL/hour; catheter for strict monitoring |
| Urinalysis | Dipstick every 4–8h; if blood 2+ — alert BMT team |
| Bladder irrigation | If haematuria established — continuous irrigation with 0.9% NaCl |
Veno-Occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome (SOS)
Pathophysiology
High-dose conditioning damages hepatic sinusoidal endothelium → fibrin deposition → obstruction of hepatic venules → portal hypertension, hepatomegaly, fluid retention.
| Clinical Feature | Detail |
|---|
| Hepatomegaly | Tender, rapidly enlarging liver |
| Weight gain | ≥5% body weight from fluid retention |
| Right upper quadrant pain | Stretching of liver capsule |
| Jaundice | Bilirubin >2 mg/dL rising |
| Ascites | Late sign — severe disease |
| Timing | Usually days +10 to +21 post-conditioning |
Diagnosis
Baltimore or Seattle criteria (clinical). Ultrasound with Doppler (reversed portal flow). Liver biopsy rarely needed.
| Management | Action |
|---|
| Defibrotide | 25 mg/kg/day IV divided q6h — first-line treatment; only approved therapy |
| Fluid restriction | Careful fluid balance — avoid volume overload |
| Diuretics | Furosemide with caution — avoid pre-renal AKI |
| Daily weight | Twice daily in high-risk patients |
| Avoid hepatotoxins | Review all medications — paracetamol dose-reduce, avoid NSAIDs |
| Anticoagulation | Avoid — risk of bleeding; defibrotide not anticoagulant |
Severe VOD mortality >80% — early detection critical
Risk factors: busulfan, TBI, prior liver disease, paediatric
Total Body Irradiation (TBI) Nursing
- Standard TBI: 12 Gy in 6 fractions over 3 days (fractionated reduces toxicity)
- Radiation safety: patient in dedicated facility; nurse PPE per radiotherapy protocol
- Positioning: standing or lying — alternate to reduce hotspots; lead lung shielding
- Acute effects: severe nausea (pre-medicate with 5HT3 antagonist + dexamethasone), parotitis (Day 0–1), fatigue, skin erythema
- Late effects: cataracts, hypothyroidism, growth retardation (paediatric), infertility, secondary malignancy
- Nursing: anti-emetics 30 min pre-TBI; monitor vitals during; comfort positioning; skin care — aqueous cream, avoid friction
Central Venous Access — Hickman / PICC Line
Essential throughout HSCT
Multi-lumen Hickman (tunnelled CVC) preferred — allows simultaneous infusion of incompatible drugs/blood products; maintained for 6–12+ months.
- Daily dressing change with chlorhexidine 2% / alcohol — sterile technique
- Cap changes per local protocol (usually every 72–96h or after each use)
- Flush with 10 mL 0.9% NaCl before/after each use; heparin lock per protocol
- Blood culture via CVC (and peripheral if possible) for every febrile episode
- CLABSI surveillance: daily inspection for redness, discharge, tenderness
- Clamp/cover when not in use; avoid kinking of external line
Nausea & Vomiting — Conditioning Antiemetic Protocol
| Drug Class | Example | Timing | Notes |
|---|
| 5HT3 antagonist | Ondansetron 8 mg IV / Granisetron | 30 min before chemotherapy, then q8–12h | First-line; constipation side-effect |
| NK1 antagonist | Aprepitant 125 mg PO Day 1, 80 mg Days 2–3 | With highly emetogenic regimens (CyTBI, BuCy) | Significant drug interactions — check tacrolimus level |
| Corticosteroid | Dexamethasone 8–12 mg IV | With each chemotherapy dose | Enhances 5HT3 efficacy; avoid in GvHD |
| Lorazepam | 0.5–1 mg PO/IV | PRN anticipatory nausea | Amnesic effect helpful; sedation risk |
| Haloperidol | 0.5–1 mg IV/PO | PRN breakthrough | D2 antagonist; useful for refractory nausea |
Day 0: Stem Cell Infusion
Day 0
Stem Cell Infusion
The "new birthday"
+7 to +14
Nadir Period
Highest infection risk
ANC ≥0.5
Engraftment
3 consecutive days
Pre-infusion Nursing Checklist (Day 0)
- 1
Pre-medication: chlorphenamine 10 mg IV + paracetamol 1g PO — 30 min before infusion
- 2
Baseline observations: BP, HR, SpO2, temperature, respiratory rate
- 3
Observations every 15 minutes during infusion — continuous SpO2 monitoring
- 4
DMSO reaction: warn patient/family of garlic/creamed-corn smell from DMSO cryoprotectant — normal; flush IV line with 0.9% NaCl; antihistamine for flushing/urticaria
- 5
Infuse over time specified on product label (usually 15–30 min per bag); thaw at bedside in 37°C water bath immediately before infusion
- 6
Document: cell count, volume infused, any reactions, observations throughout
DMSO Reactions to Monitor
Bradycardia, hypotension, nausea, haemoglobinuria (haemolysis — monitor urine), flushing, urticaria. Severe: bronchospasm (rare). Stop infusion if severe reaction — alert BMT physician.
Neutropenic Precautions
Protective Isolation
Positive-pressure single room with HEPA filtration (reduces Aspergillus risk). Strict hand hygiene (5 moments) for all staff and visitors.
- Diet: cooked food only — no raw fruit/vegetables, no salad, no undercooked meat/eggs; institutional "neutropenic diet" policy
- Water: bottled or sterile water only (no tap water in some centres)
- Visitors: no visitors with active infection/cold; limit visitor numbers; no live plants or flowers
- Procedures: avoid rectal procedures, suppositories, rectal temperature; IM injections avoided
- Skin/mucosa: electric razor only, soft toothbrush, gentle mouth care
- Environment: wipe surfaces daily with approved disinfectant; limit room exits during nadir
Infection Surveillance Protocol
| Test | Frequency | Purpose |
|---|
| FBC with differential | Daily | ANC monitoring — engraftment tracking |
| Blood cultures (CVC + peripheral) | Every febrile episode | Bacteraemia — CLABSI identification |
| Galactomannan (serum) | Twice weekly | Aspergillus screening |
| CMV PCR (plasma) | Twice weekly | CMV reactivation — treat if >threshold |
| HHV-6 PCR | Weekly (allo-SCT) | HHV-6 encephalitis risk post-SCT |
| EBV PCR | Weekly (allo-SCT) | PTLD risk in T-depleted grafts |
| CRP / Procalcitonin | Daily if febrile | Infection severity marker |
| Urine MC&S | Febrile or symptoms | UTI / haemorrhagic cystitis |
Febrile Neutropenia — Nursing Response
Definition
ANC <0.5 × 10&sup9;/L AND single temperature ≥38.3°C (or ≥38.0°C sustained >1 hour).
IMMEDIATE ACTIONS (within 1 hour)
- 1
Blood cultures ×2 — one from CVC, one peripheral (or both lumens if multi-lumen)
- 2
FBC, CRP, procalcitonin, LFTs, U&E, lactate
- 3
Piperacillin-Tazobactam 4.5g IV q6–8h — first-line broad-spectrum within 1 hour of fever
- 4
Add Vancomycin 25 mg/kg IV if: CVC-related infection suspected, skin/soft tissue source, MRSA risk, haemodynamic instability
- 5
Meropenem 1g IV q8h — if recent ESBL organism, deterioration on Pip-Tazo, or unit ESBL prevalence high
ONGOING MONITORING
- Repeat temperature q2h
- HR, BP, SpO2, RR q1h if unstable
- Urine output — target ≥0.5 mL/kg/h
- Repeat blood cultures at 48h if no defervescence
- Consider Candida/Aspergillus cover (caspofungin) if febrile >96h on antibiotics
- Galactomannan if febrile >72–96h and no bacterial source
- CT chest (low-dose) if pulmonary infiltrates or persistent fever — rule out invasive fungal
JCAHO/NICE Standard
Antibiotics within 1 hour of fever recognition — document time of fever and time of antibiotic administration.
Mucositis Grading & WHO Mouth Care Protocol
| Grade | Description | Nursing Action |
|---|
| Grade 0 | No change | Preventive care continue |
| Grade 1 | Soreness ± erythema | Rinses q2h; soft diet |
| Grade 2 | Erythema, ulcers — able to eat soft food | Rinses; analgesia (paracetamol, lidocaine rinse); soft diet; dietitian referral |
| Grade 3 | Ulcers — liquid diet only | PCA morphine; TPN initiation; regular oral suctioning |
| Grade 4 | Unable to eat/drink — severe ulceration | PCA morphine; TPN; consider bronchoscopy if airway risk; daily BMT physician review |
WHO Mouth Care Protocol — Key Steps
- Brush with ultra-soft toothbrush — no sodium lauryl sulphate toothpaste
- 0.9% NaCl (saline) rinse — 30 mL swish-and-spit, q2h while awake
- Chlorhexidine 0.12% q12h (some centres — evidence mixed)
- Lidocaine 2% viscous 5 mL PRN swish-and-spit — topical anaesthesia
- Nystatin suspension if oral candidiasis present
- Dentures removed and soaked overnight in antiseptic
- Lip care: petroleum jelly (Vaseline) to prevent cracking
Engraftment & Nutrition Recovery
Engraftment Definition
ANC ≥0.5 × 10&sup9;/L on 3 consecutive days. Typically Day +14 to +21 (peripheral blood graft); Day +21 to +28 (bone marrow); Day +28 to +42 (cord blood).
- Platelet engraftment: plt ≥20 × 10&sup9;/L unsupported for 7 days
- Chimerism testing (Day +30, +100): % donor vs recipient cells in blood/marrow
- Full donor chimerism target in allo-SCT
- Prophylactic G-CSF may be used in auto-SCT to speed engraftment
Nutritional Support
| Phase | Nutritional Strategy |
|---|
| Severe mucositis | TPN via CVC — full caloric requirements (25–35 kcal/kg/day) |
| Partial mucositis | Supplement oral with enteral (NGT) or TPN |
| Improving (Grade 1–2) | Restart soft/puree diet; dietitian-guided |
| Post-engraftment | Normal diet — neutropenic diet maintained until ANC >1.0 |
| GvHD flare | Low-fibre diet; TPN if severe GI GvHD |
GvHD Pathophysiology
In allogeneic HSCT, donor T-cells recognise host tissues as foreign (alloreactive) and mount an immune attack. GvHD is the leading cause of non-relapse mortality after allo-SCT. The same mechanism also provides graft-versus-tumour (GvT) benefit — balancing GvHD management vs GvT effect is a central challenge.
Acute GvHD (aGvHD) — <100 Days Post-HSCT
Target Organs & Presentation
| Organ | Features |
|---|
| Skin (most common) | Maculopapular rash — starts palms/soles/nape; can generalise; erythroderma in severe disease; blistering in Grade 4 |
| GI tract | Watery/green diarrhoea — high volume (up to 10 L/day in severe); nausea, vomiting, crampy pain, ileus; bloody diarrhoea Grade 4 |
| Liver | Raised bilirubin, elevated LFTs; jaundice; right upper quadrant discomfort |
aGvHD Grading (Glucksberg/IBMTR)
| Grade | Skin | GI | Liver (Bili) |
|---|
| Grade I | <25% BSA rash | None / <500 mL/day | <34 µmol/L |
| Grade II | 25–50% BSA | 500–1000 mL/day | 34–102 µmol/L |
| Grade III | >50% BSA | >1000 mL/day | 102–255 µmol/L |
| Grade IV | Bullae/desquamation | Severe ileus/bloody | >255 µmol/L |
Grade I: good prognosis
Grade IV: mortality >80%
First-Line Treatment
| Drug | Dose | Route |
|---|
| Methylprednisolone | 1–2 mg/kg/day | IV (or prednisolone PO if tolerating) |
| Continue CNI | Tacrolimus or ciclosporin — therapeutic levels | IV or PO |
Steroid-Refractory aGvHD
No response after 7 days steroids or progression after 72h. Very high mortality. Second-line: Ruxolitinib (JAK1/2 inhibitor — now FDA approved), ECP (extracorporeal photopheresis), infliximab, basiliximab.
Nursing Management — aGvHD
- Skin: emollients (aqueous cream) for rash; gentle handling; barrier creams; pressure area care if erythroderma; avoid perfumed products
- GI: strict fluid balance — replace GI losses with IV fluids; low-fibre/low-residue diet during flares; TPN if >Grade 2 GI; loperamide PRN (if no infection)
- Liver: monitor LFTs and bilirubin daily; review hepatotoxic medications; coagulation monitoring
- Infection: steroids significantly increase infection risk — increase prophylaxis; monitor CMV PCR weekly during steroids
- Psychosocial: explain GvHD to patient/family; unpredictable course causes anxiety
Chronic GvHD (cGvHD) — >100 Days Post-HSCT
Overview
Chronic GvHD resembles autoimmune diseases — fibrotic and inflammatory changes. Occurs in 40–70% of allo-SCT survivors. Classified as mild, moderate, or severe (NIH Consensus Criteria 2014).
| Organ System | Manifestations |
|---|
| Skin | Scleroderma-like changes, lichen planus, macular rash, dyspigmentation, fasciitis |
| Eyes | Keratoconjunctivitis sicca (dry eyes), photophobia, scarring |
| Mouth | Sicca syndrome — dry mouth, lichen planus, mucosal sensitivity, oral pain |
| GI tract | Oesophageal strictures (dysphagia), malabsorption, weight loss |
| Lungs | Bronchiolitis obliterans — fixed airflow obstruction, progressive dyspnoea |
| Liver | Cholestatic hepatitis, raised ALP/GGT |
| Joints/fascia | Contractures, restricted ROM, fasciitis |
| Genitourinary | Vaginal stenosis/dryness (women), phimosis (men) |
Nursing Management — cGvHD
- Skin: emollients applied twice daily; sun protection SPF50+ (photosensitivity); physiotherapy for contractures
- Eyes: preservative-free artificial tears q1–2h; cyclosporin 0.1% eye drops; moisture chamber glasses; ophthalmology review
- Mouth: rigorous oral hygiene; magic mouthwash PRN; topical tacrolimus/steroids for oral lichen planus; regular dental review
- GI: dietitian review; pancreatic enzyme replacement if malabsorption; oesophageal dilation if stricture
- Lungs (BOS): spirometry monitoring; inhaled bronchodilators; early systemic treatment; refer respiratory
- Immunosuppression monitoring: tacrolimus levels (target 5–15 ng/mL); renal function; BP; glucose (steroid-induced DM)
GvT Effect — Graft-versus-Tumour
Beneficial Mechanism
The same donor T-cells that cause GvHD also attack residual malignant cells — the GvT effect. This is why allo-SCT has lower relapse rates than auto-SCT for haematological malignancies. Over-immunosuppression eliminates GvT and increases relapse risk.
| Concept | Clinical Implication |
|---|
| Grade I–II aGvHD | May actually confer lower relapse risk — associated with GvT |
| Steroid dose | Minimise if possible to preserve GvT |
| Donor lymphocyte infusion (DLI) | Infuse more donor T-cells post-HSCT to boost GvT (e.g. for molecular relapse in CML/AML) |
| T-cell depletion | Reduces GvHD but may increase relapse — haploidentical transplants balance this |
Immunosuppression Drug Monitoring
| Drug | Target Level | Monitoring | Key Toxicities |
|---|
| Tacrolimus | 10–20 ng/mL (early); 5–10 ng/mL (tapering) | Twice weekly levels; daily renal function | Nephrotoxicity, neurotoxicity (tremor, seizures), hypertension, hyperglycaemia |
| Ciclosporin | 150–250 ng/mL (trough) | Twice weekly levels | Nephrotoxicity, hypertension, hirsutism, gingival hyperplasia |
| Mycophenolate (MMF) | MPA AUC (less common); clinical monitoring | FBC weekly (cytopenias) | GI upset, cytopenias, opportunistic infections |
| Prednisolone/Methylprednisolone | Dose-dependent; clinical response | Glucose QID; BP daily; weekly bone profile | Infection, hyperglycaemia, osteoporosis, myopathy, adrenal suppression |
| Ruxolitinib | Clinical response (GvHD) | FBC twice weekly; CMV PCR weekly | Cytopenias, CMV reactivation, Pneumocystis — ensure PCP prophylaxis |
Post-HSCT Immune Reconstitution Timeline
Full immune recovery takes 12–24 months (longer in cGvHD / ongoing immunosuppression). Innate immunity recovers first (NK cells, neutrophils), followed by B cells (3–6 months), CD8 T cells (6–12 months), and finally CD4 T cells and normal antibody responses (12–24 months).
Infection Prophylaxis Post-HSCT
| Pathogen | Prophylaxis Drug | Duration | Notes |
|---|
| Pneumocystis jirovecii (PCP) | Co-trimoxazole (TMP-SMX) 960 mg 3x/week | Until CD4 >200 × 10&sup6;/L or ≥6 months post immunosuppression | Alternate: dapsone, atovaquone, pentamidine if intolerant |
| Fungal (Candida) | Fluconazole 400 mg daily | Until engraftment + 75 days (auto) or until off immunosuppression (allo) | Switch to posaconazole/voriconazole if high mould risk |
| HSV/VZV (Herpes) | Aciclovir 400–800 mg BD | Minimum 12 months post-HSCT; longer if ongoing immunosuppression | Valaciclovir alternative; prevents VZV reactivation (shingles) |
| CMV | Letermovir 480 mg daily (allo-SCT CMV+) | Day +1 to +100 prophylaxis (primary); then PCR surveillance | Pre-emptive ganciclovir/valganciclovir if PCR >threshold |
| Bacterial | Fluoroquinolone prophylaxis during nadir (controversial) | During neutropenia period | Centre-specific; emerging resistance concern |
Secondary Malignancies
Increased Cancer Risk After HSCT
Both conditioning (TBI, alkylating agents) and chronic immunosuppression increase risk of secondary malignancies.
| Malignancy | Risk Factor | Timeline |
|---|
| PTLD (EBV-related lymphoma) | T-cell depletion, haploidentical, cord blood; high EBV load | Early (<1 year) — monitor EBV PCR weekly |
| Solid organ cancers | TBI, chronic GvHD, prolonged immunosuppression | Late (>5–10 years) |
| Squamous cell carcinoma | Skin/oral cGvHD; chronic sun exposure; ciclosporin | Years post-HSCT |
| Therapy-related AML/MDS | Alkylating agents in auto-SCT conditioning | 2–10 years |
EBV PCR weekly (allo-SCT)
Annual skin review for cGvHD patients
Endocrine Complications
| Complication | Cause | Management |
|---|
| Hypothyroidism | TBI radiation to thyroid | Annual TFTs; levothyroxine replacement if TSH elevated |
| Hypogonadism / infertility | Conditioning chemotherapy (BuCy, CyTBI) — gonadotoxic | Fertility preservation counselling and procedures BEFORE conditioning; hormone replacement therapy post-HSCT |
| Growth retardation | TBI + GH deficiency (paediatric) | Paediatric endocrinology follow-up; GH therapy |
| Adrenal insufficiency | Prolonged steroid therapy (GvHD) | Sick-day rules; steroid cover for procedures; gradual taper |
| Steroid-induced DM | High-dose steroids | QID glucose monitoring; insulin protocol; diabetic diet; refer diabetes team |
GCC Context: Fertility Counselling
Fertility preservation is particularly important culturally in GCC — religious and family values place high importance on parenthood. Sperm banking, oocyte/embryo cryopreservation, ovarian tissue cryopreservation (experimental) — all should be discussed with specialist before conditioning.
Bone Health & Cardiovascular
Osteoporosis / Osteopenia
Major complication of prolonged steroid use and hypogonadism — often underdiagnosed. DEXA scan at 1 year post-HSCT (or 3–6 months if high-risk) and annually.
- Calcium 1000–1200 mg/day + Vitamin D 800–1000 IU/day prophylactically during steroid therapy
- Bisphosphonate (alendronate/zoledronic acid) if established osteoporosis or significant osteopenia
- Weight-bearing exercise encouraged from engraftment
Cardiovascular Complications
- Cardiomyopathy: anthracycline pre-treatment + cyclophosphamide conditioning — echo at 1 year; annual in high-risk
- Metabolic syndrome: steroid use, weight gain, insulin resistance — annual lipids, glucose, BP
- Hypertension: calcineurin inhibitors (tacrolimus/ciclosporin) — BP monitoring, ACE inhibitors/CCBs
- TBI: accelerated atherosclerosis risk — smoking cessation, lipid management
Revaccination Programme Post-HSCT
Why Re-vaccinate?
HSCT wipes out the recipient's immunological memory. All vaccine-preventable disease protection is lost — patients require a full revaccination programme starting 12–24 months post-HSCT (earlier in some centres from 6 months for inactivated vaccines).
| Vaccine | Timing Post-HSCT | Notes |
|---|
| Inactivated influenza | From 6 months | Annual; safe throughout |
| Pneumococcal (PCV13 then PPSV23) | From 6 months | PCV13 first; PPSV23 8 weeks later |
| Haemophilus influenzae b (Hib) | From 6–12 months | 3-dose series |
| Meningococcal (ACWY) | From 6–12 months | Important in GCC — Hajj/Umrah exposure risk |
| Hepatitis B | From 6–12 months | Check titres post-series |
| MMR (live) | 24 months post-HSCT — only if off all immunosuppression and no active GvHD | CONTRAINDICATED if active GvHD or immunosuppressed |
| VZV/Varicella (live) | 24 months post-HSCT — same conditions as MMR | Recombinant zoster vaccine (Shingrix) preferred — safe |
IMPORTANT: Live Vaccines
Absolutely contraindicated within first 24 months, and at any time if on immunosuppression or active GvHD. Live vaccines include: BCG, yellow fever, oral typhoid, oral polio, MMR, varicella. Exception: recombinant/inactivated shingles vaccine (Shingrix) is safe.
GCC-Specific Considerations
Meningococcal vaccination essential before Hajj/Umrah — pilgrims returning to GCC are high-exposure group. Hepatitis A vaccination appropriate. Document all vaccinations in patient's BMT card.
Psychosocial Care & BMT Survivor Support
Psychosocial Challenges
HSCT is one of the most physically and psychologically demanding medical experiences. PTSD rates of 20–40% in survivors. Anxiety, depression, cognitive impairment ("chemo brain"), altered body image, sexual dysfunction, and return-to-work challenges are common.
- Psychological screening: PHQ-9 and GAD-7 at each clinic visit
- Refer to clinical psychologist/psychiatrist early — specialist BMT psycho-oncology if available
- Body image: hair loss, weight changes, skin GvHD, surgical scars — normalise and support
- Cognitive rehabilitation for "chemo brain" — occupational therapy
- Sexual health referral: hypogonadism, GvHD genital involvement — early intervention
GCC Context: Language & Cultural Support
- Arabic-language patient information essential — low health literacy in some GCC populations
- Family-centred care: family (including extended family) central to decision-making in Arab culture — include family in education sessions
- Religious coping: Islamic faith important resource — chaplaincy (hospital Imam) liaison
- Halal food requirement: ensure halal meals during neutropenic diet; involve dietitian
- BMT survivor support groups in GCC: Saudi Cancer Foundation, Emirates Cancer Society — Arabic-language support groups growing
- Return to work: societal pressure to return to work quickly — guide realistic timeline (typically 6–12 months)
Autologous vs Allogeneic HSCT — Exam Comparison Table
| Feature | Autologous | Allogeneic |
|---|
| Stem cell source | Own patient's cells | Donor (related or unrelated) |
| GvHD | None | Yes — acute and chronic |
| GvT effect | No | Yes — anti-tumour benefit |
| Immunosuppression post-HSCT | Not required | Required (tacrolimus/ciclosporin + MMF) |
| Engraftment speed | Faster (Day +10–14 peripheral blood) | Slower (Day +14–21 or longer) |
| Relapse risk | Higher (no GvT) | Lower (GvT protects) |
| Treatment-related mortality | Lower (~2–3%) | Higher (10–30% in MAC allo-SCT) |
| Main indications | Myeloma, lymphoma, germ cell tumours | AML, ALL, MDS, aplastic anaemia, sickle cell, thalassaemia |
| Conditioning | High-dose (MAC) — e.g. Melphalan 200 | MAC or RIC depending on patient fitness |
| Infection risk | Lower post-engraftment | Higher — prolonged immunosuppression + GvHD treatment |
aGvHD Grade I–IV — Quick Reference
| Grade | Skin | GI (Stool Vol) | Liver (Bilirubin) | Prognosis |
|---|
| Grade I | <25% BSA rash | <500 mL/day | <34 µmol/L | Good — topical steroids |
| Grade II | 25–50% BSA | 500–1000 mL/day | 34–102 µmol/L | Moderate — systemic steroids |
| Grade III | >50% BSA | >1000 mL/day | 102–255 µmol/L | Poor — steroid + second-line |
| Grade IV | Bullae / desquamation | Severe ileus / bloody | >255 µmol/L | Very poor — mortality >80% |
DMSO Reaction Management — Exam
DMSO (Dimethyl Sulphoxide)
Cryoprotectant in auto-SCT stem cell products. Normal side effect: garlic/creamed-corn odour — from patient's breath/sweat. Reassure patient and family — expected and normal.
| Reaction | Management |
|---|
| Garlic odour (universal) | Reassure; ventilate room; normal finding |
| Nausea/vomiting | Pre-medicate: ondansetron 8 mg IV before infusion |
| Flushing/urticaria | Chlorphenamine 10 mg IV — given as pre-medication |
| Bradycardia | Monitor ECG; atropine at bedside; slow infusion rate |
| Haemoglobinuria (red urine) | IV fluid flush; monitor renal function; urine output |
| Bronchospasm (rare) | STOP infusion; salbutamol inhaler/nebuliser; alert physician; adrenaline if anaphylaxis |
| Hypotension | IV fluid bolus; Trendelenburg position; alert BMT physician |
DHA / DOH / SCFHS / QCHP High-Yield HSCT Questions
Engraftment is the successful establishment of donor stem cells in the recipient's bone marrow with resumption of blood cell production. It is defined as ANC ≥0.5 × 10&sup9;/L on 3 consecutive days. Platelet engraftment is defined as platelets ≥20 × 10&sup9;/L without transfusion support for 7 consecutive days.
DMSO produces a characteristic garlic or creamed corn smell from the patient's breath and sweat during and after stem cell infusion. It is normal and expected — not an emergency. Pre-medicate with antihistamine and paracetamol. Warn the patient and family in advance. Monitor for actual reactions (bradycardia, bronchospasm) which are rare but serious.
Within 1 hour of fever recognition — this is the JCAHO/NICE/ESMO standard. First-line: Piperacillin-Tazobactam 4.5g IV. Add vancomycin if CVC-related infection suspected, MRSA risk, or haemodynamic instability. Switch to meropenem if ESBL organism suspected or failure to respond. Document fever time and antibiotic administration time.
VOD (Veno-Occlusive Disease) / SOS (Sinusoidal Obstruction Syndrome) is hepatic endothelial injury from conditioning chemotherapy causing hepatic venule obstruction. Clinical features: hepatomegaly, weight gain (≥5%), RUQ pain, jaundice (bilirubin rising). Treatment: Defibrotide 25 mg/kg/day IV in divided doses — the only approved treatment. Careful fluid management, avoid hepatotoxins. Severe disease mortality >80%.
Cyclophosphamide is metabolised to acrolein which is excreted in urine and toxic to bladder urothelium, causing haemorrhagic cystitis. Prevention: hyperhydration (3 L/m²/day) and mesna (binds acrolein in urine — neutralising it). Urine output target ≥200 mL/hour. Monitor urine dipstick q4–8h. If haematuria develops — bladder irrigation.
MAC (Myeloablative Conditioning): high-dose chemotherapy ± TBI that completely destroys the recipient's marrow and immune system. Used in younger, fitter patients. Higher toxicity but lower relapse. Examples: BuCy, CyTBI.
RIC (Reduced Intensity Conditioning): lower doses — partially ablates marrow; relies more on GvT effect for disease control. Used in elderly patients or those with comorbidities. Lower toxicity but higher relapse risk. Examples: Flu-Mel, Flu-Bu (low dose).
Chronic GvHD (cGvHD) is defined as GvHD occurring >100 days post-HSCT. However, this distinction is now recognised as somewhat artificial — "late acute GvHD" can occur >100 days, and overlap syndromes exist. The NIH 2014 Consensus Criteria classify cGvHD by organ involvement and severity (mild/moderate/severe) rather than time alone. Skin, eyes, mouth, lungs (bronchiolitis obliterans), and GI are most commonly involved.
Sickle cell disease (SCD) and beta-thalassaemia are the most common non-malignant HSCT indications in GCC Arab populations — driven by high carrier rates and consanguineous marriages increasing disease prevalence. KFSH&RC Riyadh performs one of the highest volumes of SCD and thalassaemia transplants globally. High consanguinity rates in Arab families also increase the likelihood of finding an HLA-matched sibling donor.
Febrile Neutropenia Antibiotic Protocol — Quick Reference
| Scenario | First-Line Antibiotic | Add |
|---|
| Standard FN (no specific source) | Piperacillin-Tazobactam 4.5g IV q6–8h | — |
| CVC-related infection suspected | Pip-Tazo 4.5g IV q6–8h | Vancomycin 25 mg/kg IV (adjust to level) |
| Skin/soft tissue infection | Pip-Tazo 4.5g IV | Vancomycin if MRSA risk |
| Recent ESBL colonisation / deterioration | Meropenem 1g IV q8h | Vancomycin if CVC/MRSA concern |
| Haemodynamic instability / septic shock | Meropenem 2g IV q8h | Vancomycin + consider antifungal (caspofungin) |
| Fever persisting >96h on antibiotics | Reassess — add antifungal | Caspofungin 70 mg loading then 50 mg daily; CT chest; galactomannan |