Chapter 78 Transplantation
Hematopoietic Stem Cell
PATHOPHYSIOLOGY
Hematopoietic stem cell transplantation (HSCT), formerly known as bone marrow transplantation, is performed for the treatment of malignancies (leukemia, lymphoma, and solid tumors), bone marrow dysfunction and failure, immunodeficiencies, and congenital metabolic disorders (Box 78-1). The bone marrow, where all blood cells originate, is involved in a number of functions: (1) transportation of oxygen throughout the body by the erythrocytes; (2) infection protection by granulocytes, lymphocytes, and monocytes; and (3) control and prevention of bleeding by platelets. The goal of HSCT is to restore bone marrow and its hematologic, and immune functions, and to reverse immune dysfunction or failure. HSCT also is used to treat and prevent further progression of genetic diseases by replacing the enzyme-deficient cells with genetically normal bone marrow and subsequently normal blood cells.
Box 78-1 Conditions Treated with Hematopoietic Stem Cell Transplantation
Malignancies: Leukemias, Lymphomas, and Solid Tumors
Bone Marrow Dysfunction or Failure
In HSCT, donor stem cells are removed, which is termed harvesting, and then transplanted into the recipient. Once the stem cells are infused into the recipient on the day of transplant, they migrate to the marrow’s spaces and eventually begin to produce new cells. Additional information on the process of transplantation is provided in the Medical Management section of this chapter.
Stem cells harvested from and transplanted back into the recipient are termed autologous; those collected from someone other than the recipient are termed allogeneic and may be matched related (from a sibling), syngeneic (from a twin sibling), matched unrelated (from a donor pool), or mismatched. Stem cells can be collected from bone marrow, peripheral blood, or the placenta and umbilical cord blood obtained after birth. Cord blood stem cells show neonatal naiveté and have less risk of viral transmission and graft versus host disease (GVHD) when compared to other sources of stem cells. Rate of engraftment following transplantation for all types of stem cells is dependent on a number of factors such as cell dose, the conditioning regimen, the recipient’s disease, and posttransplant infection. Peripheral blood stem cells engraft faster and are associated with a decreased risk of tumor contamination when compared to autologous bone marrow.
INCIDENCE
1. Survival rates following transplantation are 60% to 90%.
2. Of children under the age of 10 years, 10% develop GVHD between the second and tenth week after HSCT.
3. Among older children, 30% to 60% develop GVHD.
4. More than 70% of children lack a human lymphocyte antigen (HLA)–matched sibling.
5. Children transplanted early in their disease for chronic myelogenous leukemia have disease-free survival rates between 70% and 86%.
6. Survival rates for individuals with acute leukemia following transplantation are 30% to 60%.
7. HSCT remains the most successful treatment for children with acute myelogenous leukemia (AML) in second remission; disease-free survival is 40% in allogeneic HSCT, and 35% for autologous.
8. Patients with AML or acute lymphocytic leukemia (ALL) who receive HSCT while in remission have relapse rates of 5% to 30%. Those who receive an HSCT during a more advanced stage of disease have relapse rates of 40% to 80%.
CLINICAL MANIFESTATIONS
Clinical manifestations experienced by children during the transplant process are commonly related to the toxicities of the preparative regimen (chemotherapy with or without radiation), infection, and the occurrence of GVHD in the posttransplant period:
2. Respiratory infections, pulmonary edema
3. Hepatomegaly, venoocclusive disease, ascites
5. Renal insufficiency (increased or decreased fluid volume)
