Treatment of cancer with chemotherapeutic drugs or ionizing radiation may result in bone marrow failure and, thus, in defective blood cell formation. It is then necessary to resolve to transplantation (or surgical transfer) of hematopoietic stem cells from the bone marrow or peripheral blood, which later divide and develop mature blood cells.
Bone marrow transplantation typically accompanies the treatment of:
- primary bone marrow cancer (leukemia) — when an initial course of treatment has shown promising results, but a high recurrence risk exists;
- Hodgkin’s disease and non-Hodgkin’s lymphomas;
- localized tumors, when high-dose chemotherapy combined with total body irradiation may improve the prognosis.
There are ongoing trials investigating the effectiveness of bone marrow transplantation in patients with breast cancer.
Only a small proportion of cancer patients are selected for bone marrow transplantation. It is crucial that the transplanted bone marrow be immunologically similar (that is HLA-type matched) to the patient’s cells. The best possible donors are usually the patient’s siblings. HLA antigens of the donor marrow correspond the recipient’s marrow completely only in identical twins. It is also possible to find a suitable match in donor banks.
The patients selected for bone marrow transplantation have to be relatively young and in good general medical condition. Autologous bone marrow transplantation is usually performed in patients younger than 65, while the upper age limit for allogeneic bone marrow transplantation is typically 50 years. The risks in peripheral blood stem cell transplantation are lower, and therefore this procedure may be done in elder patients.
Low white blood cell count makes the patients particularly vulnerable to infections, and continuous antibacterial therapy is required. To protect the patients from external infections, the visits to their wards are restricted. Occasionally, even the most potent antibiotics are powerless to stop an infection from spreading until it consumes the patient.
Allogeneic bone marrow transplantation poses a high risk of graft-versus-host disease, which manifests with skin lesions, diarrhea and liver damage. This reaction may be severe and even life-threatening, and usually occurs within several months after transplantation. Preventive therapy is necessary.
Bone marrow transplantation is used in conjunction with aggressive treatment when other treatment options are ineffective.
There are two forms of bone marrow transplantation which differ in the source of hematopoietic (blood cell-forming) cells:
1. allogeneic transplantation uses other person’s bone marrow, while
2. autologous transplantation uses the patient’s own bone marrow or peripheral stem cells.
Prior to an aggressive therapeutic course, the marrow of the patient’s or donor’s femur is aspirated and frozen. After the course is completed, the marrow is reinfused intravenously. An alternative to bone marrow transplantation is peripheral blood stem cell transplantation. Stem cells are usually harvested after a course of chemotherapy, which augments their blood concentration. Naturally, chemotherapy can not be given to healthy donors, so they are administered colony stimulating factors, special proteins that stimulate formation and release of stem cells into peripheral blood.
A procedure of bone marrow transplantation consists of four steps:
1. Chemotherapy or radiotherapy is administered to minimize the tumor size. This should ideally send a transplantation candidate in remission (a state when the tumor is undetectable) thus improving the efficacy of the treatment. The treatment may, however, still be effective even if a small proportion of the tumor cells have remained.
2. Collection (or harvesting) of the donor’s or patient’s bone marrow by aspiration under general anesthesia. From several puncture sites in both femurs and in the sternum approximately 1 L of the bone marrow is aspirated. This procedure usually requires brief hospitalization and may be accompanied by malaise and fatigue. Peripheral blood stem cells are isolated by hemophoresis from blood enriched with stem cells after a course of chemotherapy and injection of a colony stimulating factor. The whole procedure of hemophoresis takes approximately 3–4 hours and is absolutely painless.
3. Antineoplastic treatment is carried out in the hospital settings for 4–5 days and consists of high doses of chemotherapeutic drugs, sometimes combined with total body irradiation. Throughout the whole course of treatment the patient usually stays in an isolation room because of high susceptibility to infections. Chemotherapeutic drugs are usually administered via Hickman catheter — a central catheter that is placed under anesthesia. To prevent nausea and vomiting the patients are given antiemetic drugs and sometimes sedated.
4. The bone marrow or peripheral blood stem cells are reinfused via the central IV line, and the cells are transported into the bones with the blood flow. However, the normal blood cell formation restores only in several weeks, during which the patient is to be closely monitored.