Hematopoietic Stem Cell Transplantation

HSCT Basics - Stem Cell Swap

• Definition: Infusion of hematopoietic stem cells (HSCs) to restore marrow function.
• Goal: Replace diseased/damaged marrow; rescue post high-dose therapy.
• Types:
  • Autologous (Auto-HSCT): Patient's own HSCs. No GVHD risk.
  • Allogeneic (Allo-HSCT): Donor HSCs. Risk of GVHD & rejection.
  • Syngeneic: Identical twin donor.
• Sources of HSCs:
  • Bone Marrow (BM): Iliac crest harvest.
  • Peripheral Blood (PBSC): G-CSF mobilized, apheresis.
  • Umbilical Cord Blood (UCB): HSC-rich, ↓GVHD, tolerates HLA mismatch.

⭐ Allogeneic HSCT requires meticulous HLA matching (A, B, C, DRB1) to prevent graft rejection and minimize Graft-versus-Host Disease (GVHD); cord blood allows for more HLA disparity.

Indications for HSCT - Entry Tickets

• Malignant Disorders:
  • Leukemias: AML (intermediate/high risk), ALL (high risk/relapsed), CML (advanced phase/TKI failure), CLL (refractory)
  • Lymphomas: Hodgkin (relapsed/refractory), Non-Hodgkin (relapsed/refractory aggressive, selected high-risk)
  • Multiple Myeloma (eligible patients)
  • Myelodysplastic Syndromes (MDS) (higher risk)
  • Myeloproliferative Neoplasms (MPN) (e.g., Myelofibrosis)
• Non-Malignant Disorders:
  • Aplastic Anemia (severe)
  • Hemoglobinopathies: Thalassemia major, Sickle cell disease (severe)
  • Immunodeficiency Syndromes: SCID, Wiskott-Aldrich
  • Inborn Errors of Metabolism: Hurler's, Adrenoleukodystrophy
  • Autoimmune Diseases (severe, refractory): Systemic sclerosis, Multiple sclerosis

⭐ Autologous HSCT is standard of care for eligible patients with multiple myeloma and relapsed aggressive lymphomas.

Pre-Transplant Protocol - The Graft Gauntlet

• Donor Selection: Crucial for outcome.

  • HLA Typing: HLA-identical sibling (best). Alternatives: Matched Unrelated Donor (MUD), Haploidentical, Cord Blood.
  • ABO Compatibility: Ideal, not essential. Manage mismatches.
  • CMV Status: Match if possible.

• Conditioning Regimens: Prepare recipient.

  • Goals: Disease eradication, marrow space creation, immunosuppression for engraftment.

  ⭐ Conditioning regimens (e.g., myeloablative like Busulfan/Cyclophosphamide, or reduced-intensity like Fludarabine/Melphalan) aim to eradicate disease and create space for donor cells.

  • Types:
    • Myeloablative (MAC): High-dose chemo ± TBI (e.g., Bu/Cy).
    • Reduced-Intensity (RIC): Lower doses, less toxicity (e.g., Flu/Mel).

• Graft Sources:

  • Bone Marrow (BM)
  • Peripheral Blood Stem Cells (PBSC) (G-CSF mobilized)
  • Cord Blood (CB) Rich in stem cells, lower Graft-versus-Host Disease (GVHD) risk typically with unrelated donors compared to adult sources, but slower engraftment.

Post-Transplant Hurdles - Stormy Aftermath

Post-HSCT period is critical, with life-threatening risks. Early recognition & management vital.

• Graft-versus-Host Disease (GVHD)
  • Acute GVHD:

    ⭐ Acute GVHD typically manifests within 100 days post-transplant, primarily affecting skin (rash), liver (jaundice, ↑bilirubin), and GI tract (diarrhea).

    • Grading: severity-based.
  • Chronic GVHD: > 100 days. Autoimmune-like; multi-organ (skin, mouth, eyes, liver, lungs).
• Infections (Timeline-based risk)
  • Early (<30 days, neutropenic): Bacterial, Candida.
  • Intermediate (30-100 days): CMV, Aspergillus, PCP.
  • Late (>100 days): VZV, encapsulated bacteria (esp. cGVHD).
• Graft Failure/Rejection
  • Primary: No engraftment.
  • Secondary: Loss of engraftment.
• Organ Toxicity
  • Sinusoidal Obstruction Syndrome (SOS/VOD): Hepatic injury (painful hepatomegaly, jaundice, fluid retention). Typically within 20-30 days.
  • Pulmonary: Idiopathic Pneumonia Syndrome (IPS), infections.
  • Nephrotoxicity: From Calcineurin inhibitors (CNIs).
• Disease Relapse
• Secondary Malignancies: PTLD (EBV-related), MDS/AML.

High‑Yield Points - ⚡ Biggest Takeaways

• Allogeneic HSCT offers cure for leukemias, lymphomas, and aplastic anemia.
• Autologous HSCT is standard for multiple myeloma and relapsed aggressive lymphomas.
• Graft-versus-Host Disease (GVHD), acute and chronic, is a major morbidity in allogeneic HSCT.
• Conditioning regimens (myeloablative/RIC) eradicate malignancy and enable engraftment.
• Prophylaxis against CMV, PJP, and fungal infections is vital post-transplant.
• Close HLA matching (donor-recipient) is crucial to prevent graft rejection and severe GVHD.