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Bone Marrow Transplant

Chelsie Sievers

Background

  • Donor selection
    • Autologous: self, no matching required (no GVHD risk, but also no graft-vs-tumor effect)
    • Allogeneic: non-self, matching based on HLA (more matched = less GVHD risk)
      • Matched-related donor (MRD): fully matched sibling
      • Matched-unrelated donor (MUD): from NMDP database
      • Haploidentical: half matched sibling or parent
  • Source of stem cells:
    • Peripheral blood stem cells (PBSCs) vs. bone marrow-derived cells vs umbilical cord
  • Conditioning regimens:
    • Myeloablative vs. reduced-intensity conditioning (RIC)
  • GVHD prophylaxis (for allo-SCT)
    • Regimen varies: can include tacrolimus, MMF, MTX, or thymo and alemtuzumab during conditioning

Complications/Adverse Effects:

  • Infectious
    • Neutropenic fever, neutropenic enterocolitis (typhlitis)
    • Bacterial infections
    • Viral infections
      • CMV: check weekly PCR levels post-allo-SCT
        • All CMV+ recipients are treated with letermovir prophylactically regardless of donor status
      • EBV: check weekly PCR levels post allo-SCT. If EBV VL >1000 on two occasions, can treat with pre-emptive rituximab to reduce the risk of PTLD
    • Invasive fungal infections (e.g. aspergillus, candida)
  • Non-infectious
    • Nausea, vomiting, diarrhea, mucositis, cytopenias
    • Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS)
      • Pathophysiology: sinusoidal endothelial cell damage from conditioning chemo -> post-sinusoidal portal HTN -> cytokine release -> multiorgan failure and death
      • Diagnosis: total bili >2, hepatomegaly/RUQ pain, weight gain > 2-5%
      • Evaluation: RUQ U/S with doppler
      • Treatment: Per heme attending; generally supportive, consider defibrotide
    • Graft failure:
      • Primary: persistent neutropenia without engraftment
      • Secondary: delayed pancytopenia 2/2 immune phenomena or infection after engraftment
    • Engraftment syndrome:
      • Pathophysiology: PMN recovery -> cytokine storm -> vascular leak
      • Symptoms: fever, tachycardia, hypotension, SOB, pulmonary edema, rash, weight gain, bone pain, confusion
      • Diagnosis: clinical
      • Treatment: high-dose IV steroids
    • Idiopathic pneumonia syndrome (IPS)
      • Umbrella term that also includes peri-engraftment respiratory distress syndrome (PERDS) and diffuse alveolar hemorrhage (DAH)
      • Pathophysiology: Lung injury from conditioning -> cytokines -> recruitment of alloreactive T cells -> progressive lung injury resembling ARDS
      • Diagnosis: multi-lobar airspace opacities and hypoxia in absence of infection
      • Evaluation: imaging, bronchoscopy with BAL
      • Management: Prednisone 1-2 mg/kg or pulse 1g/d x3 days; etanercept 2nd line
    • Acute GVHD
      • Only in allogenic; increased risk with more HLA mismatch
      • Pathophysiology: donor T cells attack recipient (Th1-mediated)
      • Symptoms: skin rash, cholestatic liver injury, diarrhea
      • Treatment: IV steroids (methylprednisolone 1-2mg/kg x 5d)
        • If refractory: mycophenolate, etanercept, ruxolitinib, antithymocyte globulin
    • Chronic GVHD (typically after T+100)
      • Can involve all organs but typically see a scleroderma-like picture (xerophthalmia, xerostomia dysphagia, arthritis, skin changes, malar rash, obliterative bronchiolitis, cholestatic liver injury, cytopenias)
      • Treatment: Steroids (also photophoresis for skin), Consider trials of ruxolitinib, ibrutinib, rituximab if refractor,
    • Post-transplant lymphoproliferative disorders (PTLD) - Pathophysiology: B-cell proliferative disease typically from latent EBV - Symptoms: fever, weight loss, fatigue, lymphadenopathy, extra-nodal masses, ↑ EBV PCR