Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cell Transplantation

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HSCT Fundamentals - Transplant Tiny Troopers

  • HSCT: Infusion of hematopoietic stem cells to replace diseased marrow, restoring hematopoiesis.
  • Purpose: Cure malignancies (leukemia, lymphoma), correct marrow failure (aplastic anemia), treat immunodeficiencies.
  • Types:
    • Autologous: Patient's own cells; rescue post-chemo. No GVHD.
    • Allogeneic: Donor cells; Graft-vs-Tumor (GVT) effect. Risk GVHD.
      • Sources: Bone marrow, PBSC, cord blood.
    • Syngeneic: Identical twin donor.
  • Pediatric Uses: ALL, AML, neuroblastoma, aplastic anemia, severe combined immunodeficiency (SCID). Sources of Hematopoietic Stem Cells for Transplant

⭐ Cord blood HSCT has lower risk of chronic GVHD but slower engraftment.

Donor & HLA - Matchmaker Mission

  • Donor Sources:

    • Syngeneic (twin): Ideal, minimal GVHD risk.
    • Allogeneic:
      • MSD: Preferred; ~25% chance per sibling.
      • MUD: Via registries; extensive search.
      • Haploidentical: Half-matched family; increasingly viable.
      • UCB: Alternative; less stringent match, slower engraftment.
  • HLA System & Matching:

    • Crucial for compatibility; prevents GVHD & rejection.
    • Key Loci: HLA-A, -B, -C (Class I) & -DRB1 (Class II).
    • Goal: High-res allele match, ideally 10/10 or 8/8 (MSD/MUD).

⭐ Matched Sibling Donor (MSD) is the gold standard, offering the best outcomes and lowest risk of severe GVHD.

Conditioning & Infusion - Pre-Game Power-Up

  • Conditioning Goals: Eradicate disease, create marrow space, immunosuppress for engraftment.
  • Regimens:
    • Myeloablative (MAC): High-dose chemo ± Total Body Irradiation (TBI).
    • Reduced-Intensity (RIC): Lower doses, relies on Graft-vs-Tumor (GVT) effect.
  • Key Agents & Side Effects:
    • Cyclophosphamide: Hemorrhagic cystitis (MESNA for prevention).
    • Melphalan: Mucositis.
    • TBI: Cataracts, endocrinopathies.

    ⭐ Busulfan toxicity includes Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS), seizures, and pulmonary fibrosis.

  • Infusion: IV, like blood transfusion, typically 24-48 hours post-chemo.
    • Monitor for DMSO reactions (especially with cord blood), volume overload.

Engraftment & Early Issues - First Few Fights

  • Engraftment: (ANC > 0.5 x $10^9/L$ for 3 days; Platelets > 20 x $10^9/L$ for 7 days, no transfusion). Occurs 2-4 weeks.
  • Early Complications (<100 days):
    • Febrile Neutropenia: Fever + neutropenia. Sepsis risk. Broad-spectrum antibiotics.
    • Mucositis: GI inflammation/ulceration. Supportive care.
    • Graft Failure: Primary (no engraftment) or Secondary (loss post-engraftment).
    • SOS/VOD: Hepatic sinusoidal damage. Tx: Defibrotide.

      ⭐ VOD/SOS is characterized by painful hepatomegaly, jaundice, and fluid retention/weight gain, typically diagnosed using Baltimore or modified Seattle criteria.

    • Acute GVHD: Donor T-cells attack recipient skin, liver, gut. Immunosuppressants. oka

GVHD & Late Effects - Long-Term Lookout

  • Graft-versus-Host Disease (GVHD):
    • Acute: <100 days. Targets: Skin (rash), Liver (jaundice), GIT (diarrhea).
    • Chronic: >100 days. Autoimmune features; affects skin, eyes, mouth, lungs (BOS).
    • Prophylaxis: Calcineurin inhibitors (CNI), MTX. Treatment: Corticosteroids.
  • Late Effects (Post-HSCT):
    • Endocrine: Hypothyroidism, gonadal failure (infertility), growth issues (↓).
    • Organ damage: Lungs (BOS), kidneys (CKD), heart (cardiomyopathy).
    • Secondary Cancers: PTLD, solid tumors (e.g., skin).
    • Infections: Prolonged risk (CMV, VZV, fungal).
    • Neurocognitive & psychosocial impact.
  • Long-Term Follow-Up: Crucial for early detection & management.

⭐ Acute GVHD typically occurs within the first 100 days post-transplant and primarily affects skin, liver, and gastrointestinal tract.

Chronic GVHD Skin and Mouth Scoring

High‑Yield Points - ⚡ Biggest Takeaways

  • HSCT offers cure for various malignant (e.g., leukemia) and non-malignant (e.g., aplastic anemia, thalassemia) pediatric diseases.
  • Stem cell sources include bone marrow, PBSC, and UCB; HLA matching is critical, with sibling donors being preferred.
  • Conditioning regimens (chemotherapy ± radiotherapy) are used for myeloablation and immunosuppression before transplant.
  • Major complications include Graft-versus-Host Disease (GVHD) (acute and chronic), infections (especially CMV), veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), and graft failure.
  • Engraftment is signaled by rising neutrophil (ANC >500/µL) and platelet counts ( >20,000/µL), typically within 2-4 weeks.
  • Chimerism analysis is crucial post-transplant to monitor donor cell engraftment and detect early relapse or graft rejection.
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Which of the following methods can be used to prevent graft-versus-host disease in bone marrow transplantation?

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Pediatric NHL is usually _____ grade and has a good outcome

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