hematopoietic stem cell transplantation (HSCT)

Introduction

Intravenous infusion of hematopoietic progenitor cells to establish bone marrow & immune function after ablation of host bone marrow.

Classification

Types of HSCT:

• autologous
  • stem cell harvesting from patient prior to high-dose chemotherapy &/or radiation
  • cryopreservation
  • reinfusion into the patient after chemotherapy to restore hematopoiesis
• allogeneic
  • HLA-matched donor
  • HLA-identical sibling
  • HLA-identical donor identified from the general population via searching international donor registries
  • in some case, one antigen mismatch from a sibling may be tolerated
  • allogeneic cells from fetal cord blood (rich in stem cells) may be associated with less graft-versus host disease

Phases post HSCT

• pre-engraftment phase 1 (< 30 days post HSCT)
  • profound neutropenia distinguishes HSCT from other organ transplantation
• post-engraftment phase 2 (30-100 days post HSCT)
• late phase 3 (> 100 days post HSCT)

Indications

• hematopoietic malignancies
  • acute leukemia
  • lymphoma
  • myeloma
  • high-risk myelodysplastic syndrome
• aplastic anemia
• genetic blood disorders
  • thalassemia
  • sickle cell disease
  • severe combined immunodeficiency
• support for high-dose chemotherapy in which hematopoietic toxicity limits therapy (autologous HSCT)
  • breast cancer
  • germ cell cancers
  • cancer of the ovary

Laboratory

• monitoring cytomegalovirus DNA with pre-emptive therapy preferred to prophylaxis with ganciclovir

Procedure

allogeneic hematopoietic stem cell transplantation

• whole body irradiation
• myeloablative high-dose chemotherapy
• stem cell transplantation
  • longer donor leukocyte telomeres improves 5-year survival in anemia patients
• immunosuppressive therapy to prevent transplant rejection & graft-vs-host disease

Complications

• graft versus host disease (GVHD) (allogeneic HSCT)
  • acute GVHD generally occurs within 3 months of transplantation
  • chronic GVHD may occur with taper of immunosuppression
  • risk of infection much greater after allogeneic HSCT than autologous HSCT because of myeloablative conditioning with a prolonged period of neutropenia & immunosuppression to suppress graft vs host disease
• opportunistic infections
  • pancytopenic phase 1 (< 30 days post transplantation)
    • invasive pulmonary aspergillosis in neutropenic patients
    • Herpes simplex virus
    • facultative gram negative bacilli
    • Staphylococcus epidermidis
    • gastrointestinal streptococci
    • Candida
  • phase 2 (30-100 days post transplantation)
    • cytomegalovirus pneumonitis (allogeneic HSCT)
      • generally occurs within 3 months of transplantation
    • Epstein-Barr virus*
    • Staphylococcus epidermidis
    • Candida
    • invasive pulmonary aspergillosis
    • Toxoplasma gondii*
    • Strongyloides stercoralis*
    • Pneumocystis jirovecii (late phase 2)
  • phase 3, late complications (> 100 days post transplantation)
    • increased risk of infection with encapsulated organism
      • Streptococcus pneumoniae
    • cytomegalovirus pneumonitis
    • Varicella zoster reactivation (20-50%)
      • dermatomal pain with vesicular rash
      • disseminated vesicles with visceral involvement; liver, lung, brain
    • Epstein-Barr virus*
    • invasive pulmonary aspergillosis
    • Pneumocystis jirovecii
    • Toxoplasma gondii*
    • BCNU-related interstitial pneumonitis with autologous HSCT
  • respiratory & enteric viruses (all phases post transplantation)
  • risk of infection much higher with allogeneic than autologous transplantation due to myeloablative conditioning, neutropenia, immunsuppression to reduce graft vs host disease
• bone marrow transplant nephropathy
• veno-occlusive disease of the liver, especially after chemotherapy with busulfan
• risk of secondary malignancy (allogeneic HSCT)
  • skin
  • buccal cavity
  • central nervous system
  • thyroid
  • connective tissue
• excess risk for adverse cardiovascular outcomes
  • hazzard ratio ~ 2-3
• excess risk of all-cause mortality
  • hazzard ratio ~ 10

* low incidence (< 10%

Management

• rapid hematologic & immunologic reconstitution is generally complete within 3-6 months
• allogeneic HSCT is treated for 6-12 months after transplantation with immunosuppressive agents to prevent allo-recognition of the patient by donor T-cells
• prescribe new medications with caution
  • anti-rejection drug effects are wide
  • drug interactions are common
• immunizations prior to transplantation
  • see organ/tissue_transplantation
• reimmunizations after HSCT
  • diptheria
  • tetanus
  • poliovirus (inactivated)
  • Haemophilus influenzae B
  • pertussis
• antifungal prophylaxis
  • fluconazole 6-12 mg/kg/day (max 400 mg/day) (IV or PO) from the start of conditioning until engraftment
  • echinocandin is an alternative to fluconazole
  • prophylaxis with fluconazole & a fluoroquinolone for neutropenic patients
• CMV prophylaxis
  • monitoring cytomegalovirus DNA with pre-emptive therapy preferred to prophylaxis with ganciclovir
  • formerly, indicated for transplant recipients at risk for CMV
  • ganciclovir, valganciclovir or high-dose acyclovir
  • can reduce risk of lymphoproliferative disease
• Bactrim is used for prophylaxis against & treatment of Pneumocystis pneumonia
• treat complications
  • BCNU-related interstitial pneumonitis is treated with glucocorticoids to prevent respiratory failure & death
• treatment of graft versus host disease (GVHD)
• complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity
• lifelong surveillance for long-term complications

More general terms

• organ transplantation

More specific terms

• bone marrow transplantation (BMT)

Additional terms

• bone marrow transplant (BMT) nephropathy
• graft versus host disease (GVHD)
• vaccination after bone marrow transplantation