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- The principles of and approaches to the critical care of hematopoietic stem cell transplant recipients are similar to those for other immunosuppressed hosts.
- Specific complications tend to occur within well-defined time periods and are influenced by the type of stem cell transplant.
- The primary distinguishing features of hematopoietic stem cell transplant recipients are the high prevalence of graft rejection, graft-versus-host reactions, and chemoradiotherapy-related toxicities.
- Acute graft-versus-host disease represents a major problem to allogeneic hematopoietic stem cell transplantation.
- Hepatic veno-occlusive disease is the most common lethal chemoradiotherapy-related toxicity after hematopoietic stem cell transplantation.
- When prophylactic treatment is used, diffuse pneumonia due to cytomegalovirus is uncommon after hematopoietic stem cell transplantation.
- Idiopathic pneumonia syndrome remains a major cause of mortality, and no treatment has been proved effective.
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Transplantation of human marrow precursors (hematopoietic stem cell transplantation [HSCT]) has become the primary therapy for several malignant and nonmalignant diseases. HSCT serves as a “salvage” therapy for restoring marrow function after marrow-ablating doses of chemoradiotherapy have been given to eradicate malignant cells in leukemias, myelodysplastic syndromes, multiple myeloma, malignant lymphomas, and assorted solid tumors, such as breast carcinoma and neuroblastoma. HSCT also can be used to replace dysfunctional hematopoietic or lymphoreticular precursors and to correct congenital or acquired deficiencies, such as aplastic anemia, thalassemia, and congenital immune-deficiency syndromes.1
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Antigenic differences between the marrow donor and recipient may result in graft rejection or, since the marrow graft contains immunocompetent lymphocytes, may initiate graft-versus-host (GVH) reactions. The antigenic determinants that mediate tissue graft rejection responses are primarily the human leukocyte antigens (HLAs). These are encoded by genes of the major histocompatibility complex (MHC) located on chromosome 6.
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Donor marrow precursor stem cells may be obtained from several sources. Autologous hematopoietic stem cells from the marrow or peripheral blood of the patient can be used in the treatment of malignant disease if the cells are free of malignancy and were harvested before chemoradiotherapy conditioning. This type of material can be cryopreserved for an extended period prior to reinfusion. Syngeneic stem cells from an identical twin also are ideal because they are genetically indistinguishable from those of the recipient.
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In many cases, HSCT is undertaken with allogeneic but phenotypically similar marrow or peripheral blood stem cells. In the best case, an HLA-identical sibling is available to serve as the donor, thus minimizing the antigenic disparity. Siblings have a 25% chance of being HLA identical. Allogeneic HSCT also may be performed using partially HLA-matched donor sources. International tissue typing banks may make it possible to identify unrelated volunteer donors who are HLA identical.
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Immunologic Alterations
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Intensive chemoradiotherapy conditioning regimens produce predictable alterations in host defenses related to granulocytopenia and ablation of humoral and cell-mediated immunity. Circulating granulocytes generally recover within the first 3 weeks after marrow infusion. Normal numbers of lymphocytes are seen within a month after HSCT, but antibody production is often delayed for 3 ...