2.6 Hematopoietic Stem Cell Transplantation (HSCT/BMT)

2.6 Hematopoietic Stem Cell Transplantation (HSCT/BMT)

Hematopoietic Stem Cell Transplantation (HSCT) is an intensive, potentially curative procedure for hematologic malignancies (e.g., acute leukemias, aggressive lymphomas, multiple myeloma) and non-malignant hematologic disorders. HSCT involves eradication of the host immune system and malignant clones using high-dose conditioning therapy, followed by infusion of hematopoietic stem cells to re-establish blood cell production.

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Transplant Modalities & Stem Cell Sources

1. Autologous HSCT

• Source: Patient's own hematopoietic stem cells harvested during clinical remission, cryopreserved, and re-infused following high-dose chemotherapy.
• Clinical Purpose: Allows administration of supra-lethal doses of cytotoxic chemotherapy to eradicate residual malignant cells; stem cells serve solely as a rescue product to restore bone marrow function.
• Immunological Features: Zero risk of Graft-versus-Host Disease (GVHD); however, there is no Graft-versus-Tumor (GVT) effect, carrying a higher relapse risk compared to allogeneic transplant.

2. Allogeneic HSCT

• Source: Hematopoietic stem cells harvested from a Human Leukocyte Antigen (HLA)-matched donor—either a Matched Related Donor (MRD; e.g., sibling), Matched Unrelated Donor (MUD), or Haploidentical donor (50% match; parent/child).
• Clinical Purpose: Eradicates host marrow and establishes a new donor immune system.
• Immunological Features: Donor T-cells recognize residual recipient tumor cells as foreign, exerting a beneficial Graft-versus-Tumor (GVT) effect. However, donor T-cells also attack normal recipient host tissues, causing Graft-versus-Host Disease (GVHD).

3. Umbilical Cord Blood (UCB)

• Source: Stem cells collected from newborn placenta/umbilical cord blood.
• Features: Less strict HLA-matching requirements due to immunologically naive T-cells; however, low total cell dose results in delayed engraftment and prolonged neutropenia.

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Conditioning Regimens

Conditioning is administered prior to stem cell infusion (Days -7 to -1) to eradicate malignant cells, create space in bone marrow niches, and suppress host immunity to prevent graft rejection.

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Graft-versus-Host Disease (GVHD)

GVHD is a major cause of morbidity and mortality following allogeneic HSCT. It is mediated by donor T-lymphocytes that recognize histocompatibility antigens on recipient target tissues as foreign.

1. Acute GVHD (aGVHD)

• Onset: Historically defined as occurring within 100 days post-transplant (classic aGVHD).
• Primary Target Organs: Skin (maculopapular rash), Liver (cholestatic jaundice, elevated bilirubin), and Gastrointestinal Tract (secretory diarrhea, mucosal sloughing, severe abdominal cramps, ileus).

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|                                ACUTE GI GVHD STAGING (BY DIARRHEA VOLUME)                               |
| Stage 1:  Diarrhea volume 500 - 1,000 mL/day (or 10-15 mL/kg/day in pediatrics).                         |
| Stage 2:  Diarrhea volume 1,001 - 1,500 mL/day (or 16-20 mL/kg/day).                                    |
| Stage 3:  Diarrhea volume 1,501 - 2,000 mL/day (or 21-25 mL/kg/day).                                    |
| Stage 4:  Diarrhea volume >2,000 mL/day (or >25 mL/kg/day), OR severe abdominal pain, ileus, bloody stool.|
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2. Chronic GVHD (cGVHD)

• Onset: Typically occurs >100 days post-transplant, resembling autoimmune disorders (e.g., systemic sclerosis, Sjögren's syndrome).
• Clinical Manifestations: Sclerodermatous skin changes, oral sicca syndrome (dry mouth, mucosal lichenoid lesions), esophageal web/stricture formation, bronchiolitis obliterans (lung damage), chronic cholestatic liver disease, and widespread malabsorption.

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Nutritional Management Across HSCT Phases

Phase I: Hyperacute & Engraftment Phase (Days 0 to +30)

• Clinical Status: Profound neutropenia (ANC <500/mcL), severe Grade 3–4 mucositis, intractable nausea, vomiting, and diarrhea.
• MNT Interventions:
  • Parenteral Nutrition (PN) Indication: Standard indication when oral intake is anticipated to be <50–60% of estimated energy/protein requirements for >7–10 days due to severe mucositis or gut toxicity.
  • PN Prescription: Central line administration; non-protein calories provided as dextrose and IV lipid emulsion; protein provision 1.5–2.0 g/kg body weight/day to offset severe catabolism.
  • Food Safety / Infection Control: Rigorous safe food handling guidelines (avoiding raw or undercooked meats, unpasteurized dairy, unwashed fruits/vegetables) to minimize neutropenic infection risks.

Phase II: Acute GI GVHD Management (Gut Rest & Trophic Feeding)

When acute GI GVHD presents with massive secretory diarrhea (>1.5–2.0 L/day), severe abdominal cramping, or ileus, aggressive nutritional staging is essential to allow mucosal healing.

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|                              4-PHASE DIETARY REINTRODUCTION PROTOCOL                                    |
| Phase 1 (Gut Rest):     Complete NPO with Total Parenteral Nutrition (TPN) during severe diarrhea        |
|                         (>1,000-1,500 mL/day) and abdominal pain.                                       |
| Phase 2 (Trophic Feed): Initiate isotonic, lactose-free, low-fat, low-residue clear liquids            |
|                         (e.g., oral rehydration solutions, diluted elemental formulas) when diarrhea     |
|                         decreases to <1,000 mL/day.                                                      |
| Phase 3 (Soft Diet):    Introduce low-fat (<20-30g/day), low-fiber, lactose-free, non-irritating soft    |
|                         solids as diarrhea stabilizes at <500 mL/day.                                    |
| Phase 4 (Regular):      Gradual reintroduction of healthy fat, fiber, and intact milk protein as         |
|                         immunosuppressive steroids are tapered and gut function normalizes.             |
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Phase III: Chronic GVHD & Long-Term Recovery

• Steroid-Induced Osteoporosis: High-dose systemic corticosteroid therapy (e.g., prednisone) causes severe bone loss and osteonecrosis.
  • MNT: Supplemental Calcium (1,200 mg/day) and Vitamin D (1,000–2,000 IU/day); routine DEXA bone density screening.
• Oral Sicca & Dysphagia: Artificial saliva, high-calorie liquid nutrition supplements.
• Immunosuppression Maintenance: Continued vigilance with food safety and nutritional monitoring until all immunosuppressive agents are discontinued.