Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

Definition

• A procedure in which a patient receives hematopoietic stem cells from a donor (matched sibling, unrelated donor, haploidentical, or cord blood). which challenge
• Provides both marrow rescue and a therapeutic graft-versus-tumor (GVT) effect, but carries risk of graft-versus-host disease (GVHD).

Indications

• Acute leukemias (AML, ALL) – high-risk or relapsed
• Myelodysplastic syndromes (MDS)
• Chronic leukemias – e.g., CML resistant to TKIs, high-risk CLL (rare now)
• Aplastic anemia & bone marrow failure syndromes
• Lymphomas & myeloma – selected cases (relapsed/refractory)
• Inherited disorders – thalassemia, sickle cell disease, immunodeficiencies

Types of Allo-HSCT Donors

• Matched Related Donor (MRD) – HLA-identical sibling
• Matched Unrelated Donor (MUD) – HLA-matched volunteer donor
• Mismatched / Haploidentical – “half-match” (parent/child/sibling) → newer strategies with post-transplant cyclophosphamide
• Umbilical Cord Blood – rich in stem cells, allows less strict HLA matching

Conditioning Regimens

1. Myeloablative (MAC):
   • High-dose → irreversible marrow ablation
   • Examples: Busulfan + Cyclophosphamide (BuCy), Cyclophosphamide + TBI
   • Younger, fit patients
2. Reduced-Intensity (RIC):
   • Lower-dose chemo/radiation → mixed chimerism, relies on GVT effect
   • Examples: Fludarabine + Melphalan, Flu + Bu (low-dose)
   • Older or comorbid patients
3. Non-myeloablative (“Mini”):
   • Minimal cytopenias, mostly immunosuppressive
   • Example: Fludarabine + low-dose TBI

Major Complications

1. Graft-Versus-Host Disease (GVHD)

• Acute GVHD: usually <100 days post-transplant
  • Skin rash, liver dysfunction, diarrhea
• Chronic GVHD: >100 days, resembles autoimmune disease (skin, eyes, lungs, joints)
• Prevention (pharmacist focus):
  • Calcineurin inhibitors: cyclosporine, tacrolimus
  • Methotrexate (low-dose), mycophenolate mofetil (MMF)
  • Post-transplant cyclophosphamide (PTCy) in haploidentical HSCT
  • Newer: JAK inhibitors (ruxolitinib) for refractory GVHD

2. Infections

• Early (0–30 days): bacterial (gram-negative sepsis), fungal (candida, aspergillus), viral (HSV, CMV reactivation)
• Intermediate (30–100 days): CMV, EBV (→ PTLD), fungal, PCP
• Late (>100 days): VZV reactivation, encapsulated bacteria (due to poor immune reconstitution)

3. Organ Toxicities

• Veno-occlusive disease (VOD/SOS) – busulfan, cyclophosphamide, inotuzumab, gemtuzumab
• Pulmonary – idiopathic pneumonia syndrome, BOOP, pulmonary fibrosis
• Renal/cardiac – drug toxicities (cyclosporine, tacrolimus, anthracyclines)

Supportive Care (Pharmacist Role)

• Antimicrobial prophylaxis:
  • Antiviral: acyclovir (HSV, VZV); letermovir (CMV prophylaxis in high-risk allo)
  • Antifungal: fluconazole or mold-active azole (posaconazole/voriconazole if GVHD/immunosuppressed)
  • PCP: TMP-SMX (start after engraftment, continue ≥6–12 months)
• GVHD prophylaxis & immunosuppressant monitoring
  • Tacrolimus & cyclosporine → trough level monitoring, nephrotoxicity, hypertension, electrolyte disturbances
• Vaccinations: restart 6–12 months post-HSCT (no live vaccines until immune recovery)
• Growth factors: filgrastim in prolonged neutropenia
• Fertility preservation before transplant conditioning

Pharmacist Key Monitoring

• Calcineurin inhibitor drug levels
• Busulfan pharmacokinetics (TDM) to reduce VOD risk
• Drug interactions: azoles ↑ calcineurin inhibitors & busulfan; anticonvulsants affect PK; nephrotoxic combos (aminoglycosides, amphotericin, tacrolimus)
• Early recognition of GVHD, VOD, and infections

Advantages vs Auto-HSCT

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