Bone Marrow Transplant

Bone Marrow Transplant – Michael LaPelusa

Background

  • Donor selection
    • Autologous: self, no matching required
    • Allogeneic: non-self, matching based on HLA (more matching -> 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
    • Timeline for transplant:T -14 d: cell mobilization and collection (G-CSF used to help mobilize stem cells)
    • T -8 d to T-3d: conditioning regimen, initiation of GVHD ppx, TLS ppx and sinusoidal obstruction syndrome ppx
    • T = 0 d: transplant
    • T +7 d to T +30 d: engraftment

 

Complications/Adverse Effects:

  • Infectious: Neutropenic fever, typhlitis, GNR, HSV, respiratory/enteral viruses (adenovirus, RSV, parainfluenza), Aspergillus, Candida
  • Non-infectious   
    • Nausea, vomiting, mucositis
    • Cytopenia’s: Transfuse as needed (plt >10, hematocrit >21)
    • Hepatic veno-occlusive disease/sinusoidal obstructive syndrome:
      • 2/2 cytotoxic venule damage from chemo resulting in thrombi formation
      • Diagnosis: T Bili >2, hepatomegaly/RUQ pain, weight gain > 2-5%  
      • Evaluation: RUQ US with doppler
      • Treatment: Per heme attending; Consider defibrotide
    • Graft failure – primary (persistent neutropenia without engraftment) or secondary (delayed pancytopenia 2/2 immune phenomena or infection after engraftment)
    • Engraftment syndrome:
      • Pathophys: PMN recovery -> cytokine storm -> vascular leak
      • Symptoms: fever, tachycardia, hypotension, SOB, pulmonary edema, rash, weight gain, bone pain, confusion
      • Diagnosis: clinical; Workup specific symptoms
      • Treatment: high-dose IV steroids
    • Acute GVHD:
      • Only in allogenic; Increased risk with more HLA mismatch
      • Pathophys: 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+100d s/p allo)
      • Can involve all organs but typically see a scleroderma-like picture (xerophthalmia, xerostomia dysphagia, arthritis, skin changes, malar rash, obliterative bronchiolitis, cholestatic liver injury, cytopenia’s)
      • Treatment: steroids (also photophoresis for skin), consider trials of ruxolitinib, ibrutinib, rituximab if refractory
    • PTLD