Data from the International Bone Marrow Transplant Registry and the Autologous
Blood and Bone Marrow Transplant Registry indicate that approximately 20,000 HSCTs were performed for disorders of the hematopoietic system and certain solid tumors in
North America in 1998 (Table 1). The anti-tumor effect of HSCT can be achieved by
2 mechanisms. Administration of high doses of chemotherapy and, in some cases, irradiation can be used to destroy tumor cells. This conventional "myeloablative" HSCT typically results in total ablation of the host's bone marrow, and regimen-related toxicities.
An additional way to achieve an anti-tumor effect is to induce graft-versus-host disease (GVHD) or "graft-versus-leukemia" disease. In the setting of "non-myeloablative"
HSCTs, the infused stem cells eventually kill tumor cells to ultimately cure the cancer. Today, these types of HSCTs are being explored for patients who are not eligible to
receive a conventional, myeloablative HSCT.
| Acute myeloid leukemia|| Aplastic anemia
| Acute lymphoblastic leukemia || Inherited immune-deficiency disorders
| Chronic myeloid leukemia || Lymphoma
| Myelodysplastic syndrome || Congenital enzyme deficiencies
| Multiple myeloma ||
The Patient –Factors Relevant to Fungal Infections
Underlying Disease and Previous Treatment Candidates for HSCT are a heterogeneous population, an important factor in assessing risk of IFI. Previous treatment for their underlying disease –for example, chemotherapy, radiotherapy, corticosteroids, antibiotics –will have a variable effect on host defenses and the risk of infection. Many patients presenting for transplantation will have had previous infections.
HSCT Classification The source of the transplanted stem cells can be autologous, syngeneic (from an identical twin), or allogeneic, and is highly relevant to posttransplantation infectious complications.1 Patients who receive allogeneic grafts from nonmatched siblings are more likely to develop GVHD and to have suboptimal graft function and slower immune reconstitution.2 With autologous or syngeneic transplants, there is virtually no risk of GVHD and the risk of infection is low. Risk increases by 10% to 40% in recipients of allogeneic HSCT. Patients who receive an uncomplicated HLA-matched sibling transplant are at lowest risk. Risk increases if the donor is HLA-matched and unrelated. Recipients of HLA-mismatched transplants are at highest risk.
The Procedure –Factors Relevant to Fungal Infections
Conditioning treatment of underlying disease with high-dose chemotherapy with or without radiation therapy occurs before transplantation. This treatment destroys malignant cells but also ablates the bone marrow, destroying cells of the immune system. Although this preconditioning is critical to the success of the transplant, the temporary loss of immunocompetence results in a patient precariously balanced to handle potential pathogens. Until engraftment and immunologic recovery occur, the HSCT patient requires intensive supportive therapy. Factors that increase the risk for infection during this time include central venous catheters and gastrointestinal tract mucositis. Non-myeloablative transplant regimens are under study in many institutions. Although these patients may have decreased risks associated with less mucositis and neutropenia, prolonged GVHD appears to provide substantial risks for late IFI.
Course Number: V035D
This CME Expires on July 1, 2005; no tests will be accepted after this date.
This course is accredited by
The University of Pittsburgh School of Medicine, Center for Continuing Education
and The International Immunocompromised Host Society