An 8-year-old boy is brought to the hospital due to severe headache and altered mental status. An aggressive, high-risk neuroblastoma is diagnosed. As part of his treatment, the patient will receive an autologous bone marrow transplant using stem cells obtained from his peripheral blood. His pretransplant evaluation reveals a history of Epstein-Barr virus infection. This patient is at greatest risk for which of the following after transplantation?
Hematopoietic stem cell transplantation | ||
Autologous | Allogeneic | |
Donor | Patient (self) | Related/unrelated (nonself) |
Primary stem cell source | Peripheral blood | Bone marrow |
Donor cell rejection | Uncommon | Possible, depending on match |
Long-term immunosuppression | No | Yes |
Graft versus host disease | No | Possible |
Graft versus tumor activity | No | Possible |
Infection transmission | No | Possible |
Patients who undergo hematopoietic stem cell transplantation (HCT) first receive myeloablative chemotherapy, a regimen of highly cytotoxic medications that irreversibly kill existing hematopoietic stem cells. Once pancytopenia is established, patients then receive an infusion of donor hematopoietic stem cells, which engraft in the bone marrow, proliferate, and subsequently reconstitute peripheral blood cells. Donor cells are classified as allogeneic when they are obtained from a related or an unrelated donor and autologous when they are obtained from the patient (eg, preprocedure peripheral blood or umbilical cord blood banked at birth).
With autologous transplantation, the human leukocyte antigens on major histocompatibility complex class I and II molecules will be a perfect match because the donor and recipient are the same individual. Therefore, there is no risk of graft rejection (host cells attack the graft) or graft versus host disease (graft cells attack the host) because the delineation between self and nonself is preserved (Choices A, B, and C).
Although patients who undergo autologous HCT do not require ongoing immunosuppressive medications following HCT (due to the perfect match between donor and recipient), exposure to myeloablative chemotherapy causes a period of temporary, profound immunosuppression until donor cells engraft and reconstitute the peripheral blood cells. During this period of immunosuppression, chronic or latent infections may worsen. Risk is particularly high for the reactivation of human herpesviruses (eg, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, herpes simplex virus), which establish life-long latent infections and require an intact cytotoxic T-cell response for control.
(Choice D) There is little risk of transfusing a new bloodborne infection (eg, primary EBV, HIV, hepatitis virus, cytomegalovirus) in autologous HCT because the donor cells are obtained from the patient themself.
Educational objective:
Autologous hematopoietic stem cell transplantation reinfuses host cells from the patient's peripheral blood or banked cord blood to reconstitute the bone marrow. Because the reinfused cells are genetically identical to the host's, there is no risk of graft rejection or graft versus host disease. Although there is also no risk of transferring a new bloodborne pathogen, chronic or latent infections (eg, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus) may worsen due to the transient immunosuppression induced by myeloablative chemotherapy.