A Primer on BMT for New Transplant Nurses

In a session targeting novice bone marrow transplant (BMT) nurses, the Oncology Nursing Society (ONS) outlined what nurses should expect in treating BMT cases, from pretransplant to posttransplant, as well as related insurance and psychological issues affecting patients and families.

Speakers explained that advances in marrow transplantation, including histocompatibility testing, conditioning regimens, and control of graft-vs-host disease (GVHD), have brought this procedure into widespread use. By 1986, when it was clear that BMT succeeded in treating cases of acute leukemia and severe aplastic anemia by increasing survival rates from less than 20% to over 70%, 200 BMT centers performed more than 5,000 transplants annually.

Pretreatment and Treatment Phases

Of critical importance is education of the patient and family; ONS strongly encourages oncology nurses to repeatedly explain procedures and assess patient and family understanding.This is an essential element of treatment that will need to be repeated throughout therapy.

During the treatment phase, patients will be admitted to a hospital or an outpatient facility where staff will take their history, conduct a physical examination, review the transplant protocol, and perform daily care routines. Patients will undergo a preparative conditioning regimen that will assess their physiologic readiness to receive the bone marrow graft, destroy their immune system to allow for donor cell acceptance, and eliminate malignant cells.

The specific regimen depends on the patient’s disease and previous treatment. Radiation is used for immunosuppressive effects and the ability to penetrate chemotherapy-resistant sites. High-dose chemotherapy is used for antineoplastic and immunosuppressive effects. Common agents are carmustine (BCNU), busulfan (Myleran), semustine (CCNU), cyclophosphamide (Cytoxan, Neosar), cytarabine (Ara-C), cisplatin (Platinol), carboplatin (Paraplatin), daunorubicin (Cerubidine), doxorubicin, etoposide, and melphalan (Alkeran). Immunotherapy may be used for immunosuppression in severe aplastic anemia or immune deficiency disorders.

On the day of an autologous transplant, infusion of marrow or stem cells occurs 24 to 48 hours after high-dose chemotherapy; preparation includes using intravenous (IV) fluids, explaining the procedure to the patient, and premedicating the patient with steroids, analgesics, antihistamines, and anti-anxiety agents. Dimethyl sulfoxide (DMSO) will also be used to preserve stem cells and autologous marrow.

The patient receives the marrow or cells by IV push or infusion and is then placed on telemetry and monitored frequently. Side effects can include hematuria, increased bilirubin and creatinine, arrhythmias, hypertension, or allergic reactions to DMSO (eg, chills, fever, dyspnea, nausea and vomiting). If this happens, IV fluids and diuretics may be given following the infusion.

Allogeneic transplant preparation involves premedicating the patient with antiemetics, antipyretics and antihistamines; monitoring for baseline vital signs at regular intervals; and placing the patient on a cardiac monitor or pulse oximeter throughout the procedure and for 24 hours thereafter.

At the time of administration, staff must check the marrow to verify the medical record number and the patient’s name, spike the bag of marrow with straight administration set tubing, and prime and attach it directly to the patient’s central line. An IV pump and or piggybacking into other tubing are never used.

Blood return from the line should be ascertained before infusing bone marrow through the line. T-cell–depleted marrow or stem cell product is infused over 30 minutes to 1 hour, and non-T-cell–depleted marrow is infused over 3 to 4 hours.

Posttransplant Complications

Good nursing is critical during the posttransplant phase, when patients are the sickest. Engraftment and recovery may occur at different rates due to the nature of the primary disease, previously administered chemotherapy and radiation, choice of preparative regimen, choice of GVHD prophylaxis, viral complications, and the use of antimicrobial agents. Marrow cellularity gradually increases over 2 to 4 weeks.

Infection caused by various host factors or exogenous bacterial, viral, or fungal factors is a posttransplant complication. Risk factors for infection are hematologic-lymphoid disease, induction or previous treatment, preparative treatment, prolonged neutropenia and/or immune deficiency, altered mucosal barriers, microorganism colonization, and prolonged use of antibiotics.

To assess the development of infection, staff should conduct a comprehensive physical examination every 4 to 8 hours, paying special attention to the catheter site, lungs, integument, oral mucosa, and rectal area; check vital signs at least every 4 hours; and obtain complete blood count with absolute neutrophil count (ANC) daily.

Bleeding, another posttransplant complication, may occur from severe thrombocytopenia and anemia secondary to preparative regimen-induced myelosuppression; delayed patient engraftment due to GVHD, cyclosporine (Neoral, Sandimmune) prophylaxis, or marrow purging; poor graft function related to bone marrow-suppressive medications; coagulation abnormalities resulting from hepatotoxicity, GVHD, disseminated intravascular coagulation, and/or sepsis; and platelet autoantibodies.

Risk factors for bleeding include GVHD and the use of cyclosporine prophylaxis, veno-occlusive disease (VOD) with impaired production of coagulation factors, altered mucosal barriers, failed or delayed engraftment, and viral infections.

What Nurses Can Do to Avoid Complications

Nurses can take various steps to prevent posttransplant complications. These include instituting infection control practices; promoting meticulous personal hygiene to include oral and perineal areas; administering and monitoring the patient’s response to antifungal, antiviral, and antibacterial prophylaxis and treatment; carefully watching central venous catheters; imposing dietary restrictions; obtaining cultures promptly as needed; avoiding unnecessary invasive procedures (ie, enemas, rectal temperatures, bladder catheterizations, venipunctures, and finger sticks); administering cytomegalovirus-negative blood products or utilizing Pall filters in seronegative patients; and, once again, educating the patient and family about infection signs and symptoms, prophylaxis, and treatment. Washing one’s hands is still the single most important way to prevent infection.

Nursing management dictates avoiding unnecessary invasive procedures and medications (aspirin, for example) that inhibit platelet function; initiating bleeding precautions if platelets are less than 20,000/mm³; administering blood products prior to invasive procedures; testing urine, stool, and emetic fluid for occult blood; encouraging the use of soft mouth care products; giving prophylactic medications that protect from bleeding; administering IV hydration and/or bladder irrigations to prevent hemorrhagic cystitis; and applying extra pressure to sites of invasive procedures.

Patients often suffer mouth pain from oral mucositis, usually beginning just prior to transplant, peaking during the second week, and gradually receding as blood counts return; patients treated with total-body irradiation report higher levels of pain. The drug of choice is usually morphine, preferably administered by the patient rather than by continuous infusion to minimize side effects.

Veno-occlusive Disease

Veno-occlusive disease is a complication of damage to terminal hepatic venules and surrounding hepatocytes, endothelial injury and subsequent obstruction of hepatic venules and sinusoids, increased platelet consumption, and deposition of clotting factors and fibrinogen in vital organs.

With an overall incidence of 21%, VOD is a risk in the presence of hepatitis prior to transplant, repeated courses and higher doses of chemotherapy, hepatotoxic irradiation, immunosuppressive drugs that are hepatotoxic, elevated serum glutamic-oxaloacetic transaminase (SGOT) and alkaline phosphatase prior to transplant, infection or sepsis, and estrogen-progesterone therapy. Clinical signs and symptoms include hepatomegaly, upper right quadrant pain, sudden weight gain, ascites, jaundice, elevated bilirubin, high ammonia levels, coagulation abnormalities, and encephalopathy.

The focus of nursing management is to maintain intravascular volume and renal perfusion; to administer diuretics and monitor their effectiveness; to maintain restrictions of sodium, protein, and fluids; to check daily weight and abdominal girth; to avoid delivering medications that are hepatotoxic or alter mentation; to administer red blood cells and albumin; and to strictly monitor input and output.

Graft-vs-Host Disease

A major cause of morbidity and mortality in allogeneic transplantation is GVHD. Approximately 50% of patients undergoing a matched sibling transplant will develop the disease to some degree. Even more recipients undergoing matched unrelated transplants will develop GVHD, and 25% of those who do will die.

Causes include histoincompatibility between the donor and host and inability of the immunocompromised host to reject the donor cells. Risk factors include HLA compatibility, a recipient older than 20 years, gender mismatch (female to male, especially if the female has been pregnant), disease status, and prior herpesvirus infection.

Onset of acute GVHD can occur any time up to 100 days (generally, 2 to 5 weeks) after engraftment, and typically involving the skin, liver, and gastrointestinal tract. Its severity is graded by staging each of the organs involved.

Prophylaxis for GVHD, involving cyclosporine administered in conjunction with other immunosuppressive agents, is aimed at eliminating the donor T-cells or blocking their activation, and is always used with allogeneic marrow transplant. It is usually discontinued 6 months after the transplant if there is no evidence of chronic GVHD.

Since treatment for acute GVHD is very difficult and many patients go on to develop the chronic form, therapy with glucocorticoid steroids, antithymocyte globulin (ATG), zomazyme (anti-CDS antibody immunotoxin conjugate), and OKT3 (monoclonal antibody specific for CD3) should be aggressive.

Historically, the onset of chronic GVHD is defined as beginning 100 days after the transplant, but it has been documented as early as 70 days or as late as 15 months posttransplant. It usually involves the skin, liver, mouth, eyes, sinuses, vagina, and gastrointestinal tract. Two current theories are that it is a late form of acute GVHD or an alloreactivity reaction, or is the result of dysfunctional immune reconstitution.

The chronic form can be classified three ways: continuous or progressive (acute GVHD, merging into chronic), quiescent (chronic, occurring after a period during which no GVHD was evident), or de novo (chronic, presenting with no preceding acute GVHD).

Chronic GVHD is the single major determinant of long-term quality of life following BMT, but patients with limited disease have a favorable prognosis. Patients with extensive disease, however, especially if multiple organs are involved, have an unfavorable prognosis despite treatment with cyclosporine and steroids.

Informed Consent

The ONS stresses that patients be made aware of the ramifications of their disease and the special issues surrounding BMT. To ensure that patients fully understand these issues, nurses should be present for physician/patient discussions to assess the level of understanding, encourage and answer patient questions, present reinforcing information, inform the patient of nursing interventions, monitor the patient’s level of anxiety, and support the patient’s decisions.

Psychological Considerations

Bone marrow transplantation can subject patients and families to severe psychological stress. Limited insurance may force patients to fight or beg for their life, a physically and emotionally draining experience that is ultimately detrimental to patients. At least 40% of transplant patients experience a major depression and must combat anxiety and fear of death as well. The period before a transplant is particularly difficult because patients know that they have no choice and that this is their last chance of survival.

Nurses need to discuss what the patients’ support systems are, especially if they are far away from home; determine whether they are depressed; and explore with them the impact that the transplant will have on their lives.

While there is little information in the literature on the psychological implications of the donor/recipient relationship, there is evidence that patients often feel an indebtedness that they cannot repay; this can lead to conflict. If they do not progress well, they usually experience added guilt and anxiety.

 Nurses must continually assess what is happening with the patient and make sure that they keep the family informed. Family members too are suffering—rearranging their lifestyles to visit, coping with the ill family member, and trying to motivate the patient in dealing with setbacks. Weekly or biweekly meetings with the family in a neutral setting can be very helpful for dealing with these issues.