Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

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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. HSCT Engraftment Time by Stem Cell Source

⭐ 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.

Practice Questions: Hematopoietic Stem Cell Transplantation

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Which of the following is the most common myeloproliferative disorder?

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Flashcards: Hematopoietic Stem Cell Transplantation

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_____ is recommended for AML patients with _____ risk who have achieved complete remission

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_____ is recommended for AML patients with _____ risk who have achieved complete remission

HSCT; adverse

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