Bone Marrow Transplant Basics

A bone marrow transplant (BMT) is a procedure that replaces damaged or “sick” bone marrow with healthy bone marrow so that the individual can produce healthy blood cells on their own. It is utilized to treat numerous conditions such as acute leukemia, multiple myeloma, aplastic anemia, Hodgkin’s and Non-Hodgkin’s lymphoma, immune deficiencies, sickle cell disease, and neuroblastoma.

What is the function of bone marrow?

Recall that bone marrow is the spongy and nutrient dense substance found in the center of most bones. It comes in two forms: 

• Red marrow has stem cells that can differentiate into platelets, red blood cells and white blood cells. It is typically found in long bones as well as hip bones, shoulder bones and skull bones.
• Yellow marrow has stem cells that can differentiate into bone, cartilage or fat storage within the bone. It is typically found in the center of long bones.

What are the types of bone marrow transplants?

The bone marrow used for the transplant can be from a donor (allogeneic transplant) or it can come from the patient’s own bone marrow before it becomes damaged (autologous). You may also see BMT referred to as a stem cell transplant or a haematopoietic stem cell transplant (HSCT).

The key benefit of an allogeneic transplant is that the donor cells can provide an immune response to help fight off the diseased cells in the patient. The biggest risk with this type of transplant is graft-versus-host disease.

The key benefit of autologous transplant is there is no risk for graft-versus-host disease (GvHD), and there is no need to find a suitable match. The main risk for this type of transplant is that there is no donor immune system protection, so there is a greater chance of relapse.

A subtype of allogeneic transplant is the syngeneic transplant where the donor is an identical twin. The obvious key benefit of this type of transplant is that the twins are an exact match so there is a very low chance of GvHD. Additionally, the potential for the donor cells to grow within the patient (engraftment) is higher. However, since the donor immune system is nearly identical to the recipient’s immune system, the new cells may not recognize and fight off the cancer cells, leading to a higher incidence of relapse.

What are the options for obtaining stem cells?

Stem cells can be obtained from bone marrow, peripheral blood stem cells (PBSC) and umbilical cord blood. 

To obtain stem cells from bone marrow, the donor is placed under anesthesia and bone marrow from the iliac crest is removed via needle aspiration. Peripheral blood cells are obtained via an IV catheter much in the same way that blood is donated.

In an allogeneic transplant, the donor is given medication to stimulate the production of stem cells for four to six days prior to the collection. The donor cells can be collected from the bone marrow or from the donor’s blood via an IV catheter, which is the most common method of collection.

The blood is then centrifuged to separate the stem cells from the other blood components. The blood components are returned to the donor, and the stem cells are utilized for the recipient. 

Prior to the stem cell infusion, the recipient goes through a stage called “conditioning and treatment.” In this stage, the recipient undergoes high-dose chemotherapy (with or without radiation) to kill off cancer cells and to purposefully weaken the immune system so the body doesn’t reject the donor cells as readily. 

In an autologous transplant, the patient is given medications that cause the body to produce and release more stem cells into the bloodstream. This is called “stem cell mobilization.” The patient then has their stem cells collected from either their bone marrow or the blood. The blood is processed through the centrifuge that removes the stem cells and the rest of the blood is returned to the patient.

In the “conditioning and treatment” stage, the patient undergoes high-dose chemotherapy (they may or may not also receive radiation) to kill off the remaining cancer cells while also killing off any blood-producing cells left in the patient’s bone marrow. When the patient is ready (about 17 days after chemotherapy), the frozen stem cells are thawed and reintroduced into the patient. 

Benefits of obtaining stem cells from peripheral blood over the bone marrow is that cells obtained via peripheral blood tend to be more mature which can lead to earlier engraftment. Peripheral collection also does not require the donor to undergo a surgical procedure and anesthesia. The downsides to peripheral collection is that it can take multiple sessions over multiple days to get enough stem cells for transplant. 

What about umbilical cord blood?

Umbilical cord blood can be utilized for stem cell donation by removing blood from the umbilical cord immediately after birth. The blood is tested, frozen and stored for potential later use. The benefits of this type of collection is that the cells are not differentiated so they can be used for donors who cannot find a compatible HLA match. It is also easy to obtain stem cells in this manner and does not put the child or the parent at risk.

A potential downside to this method is that genetic conditions could be transferred to the recipient and, since the cells are not differentiated at all, engraftment can take longer.

How is a match determined?

HLA matching utilizes PCR to look at DNA segments that encode the human leukocyte antigens to determine if they are similar enough for a quality match. If the quality of the match is low, the patient is at higher risk for developing graft-versus-host disease (GvHD), which is a serious and life-threatening complication. 

Patients are most likely to match with a donor who is their same ethnicity, and an even greater likelihood when the potential donor is within their own family. In fact, a patient has about a 30% chance of finding a matched donor within their family, and there’s a 25% chance that a sibling will be a match.

What is engraftment?

Engraftment is essentially when the recipient’s body “takes on” the newly transplanted cells and they begin to grow in the bone marrow. In order for the stem cells to rescue the patient after his or her bone marrow has been depleted by high-dose chemotherapy/radiation, the stem cells must be able to survive and grow in the patient’s bone marrow. The average time to engraftment ranges from 14 to 21 days and can depend on the type and method of transplant as discussed above.

What are the complications of bone marrow transplant?

There are several serious complications that can occur with bone marrow transplant. These include: 

• Graft-versus-host disease (GvHD)
• Infection
• Mouth sores
• Nausea, vomiting, diarrhea
• Changes in taste or loss of taste
• Malnourishment
• Fluid volume overload
• Engraftment syndrome – A condition characterized by fever, rash, diarrhea, pulmonary infiltrates and neurological symptoms after autologous stem cell transplant.
• Veno-occlusive disease – This condition causes liver damage, hepatomegaly, jaundice, and ascites. When severe it can lead to multi-organ failure and death (the mortality rate is greater than 80%). It is more likely to occur in patients who are very young (less than 1 year old), who have prior liver or kidney disease, have advanced malignancy or who are on total parenteral nutrition (TPN). It is also more likely in those undergoing allogeneic transplant with unrelated donors, those with poorly matched donors, patients who received certain medications including cyclophosphamide, busulfan, methotrexate and cyclosporine, and in patients who have undergone multiple autologous transplants with poor prognosis.
• Hemorrhagic cystitis – The manifestations can range from microscopic hematuria to significant hemorrhage and renal failure.
• Hepatorenal syndrome – About 15% of patients who receive BMT experience renal failure, and this is often due to veno-occlusive disease.

Now that you have some foundation knowledge about bone marrow transplant, let’s dive into the nursing implications using the Straight A Nursing LATTE method.

L: How does the patient LOOK?

If the patient has undergone an autologous transplant utilizing bone marrow aspiration, they will initially have pain and bruising at that site over the iliac crest.

Other signs and symptoms associated with bone marrow transplant are going to be closely related to those of chemotherapy and radiation since those treatment modalities are utilized for the conditioning stage. Common signs and symptoms include: 

• Nausea, vomiting, diarrhea
• Fatigue
• Mucositis (inflammation and or sores in the mouth)
• Weight loss
• Pancytopenia while the patient is waiting for engraftment to occur

Additionally, patients will exhibit signs and symptoms specific to any post-BMT complications they may experience. Due to the high number of potential complications, this list is extensive and will vary from patient to patient. 

A: How do you ASSESS the patient who has undergone BMT?

The main goal of your assessments will be to monitor your patient closely for complications and signs of deterioration. This includes:

• Take vital signs frequently with a specific focus on the patient’s temperature as this is often a sign of infection. After bone marrow transplant, a patient is generally considered to have a fever when their temperature is above 38-degrees Celsius or 100.4-degrees Fahrenheit.
• You’ll also monitor closely for signs of fluid overload. This includes taking daily weights, keeping strict count of all I/Os, monitoring for edema and auscultating lung sounds.
• Monitor for signs of respiratory distress, which can be related to fluid overload or other complications such as GvHD or pneumonia. Assess respiratory rate, O2 saturation, lung sounds and work of breathing. 
• Monitor for the early signs of GvHD, which involves a burning, red rash that can occur anywhere including in the buccal mucosa. 
• Assess for pain related to bone marrow aspiration or complications such as mucositis, GvHD or veno-occlusive disease.
• Assess your patient’s risk for falls. They may have an unsteady gait and be weak after the transplant due to deconditioning, weight loss, malnourishment, loss of muscle mass, potential neurotoxic medications and GvHD. 
• Because platelets are low in the initial post-BMT period, assess your patient’s bleeding risk and for signs of bleeding. 
• Monitor your patient for signs of Infection, keeping a very close eye on things like Foley catheters, urine clarity (or cloudiness) and central venous catheters. 

T: What TESTS will be utilized for a patient undergoing BMT?

Before transplant

• Prior to consideration for a bone marrow transplant, the patient will undergo a bone marrow biopsy or bone marrow aspiration. This test allows the MD to see specific abnormalities in the quality or quantity of the blood components. 
• HLA matching (also called “tissue typing”) involves blood draws of both the patient and the donor. This is not necessary in an autologous transplant.
• Other blood tests screen the patient for infectious disease such as hepatitis, HIV, cytomegalovirus (CMV), toxoplasmosis, herpes simplex virus and varicella zoster (there are others!).
• Renal and hepatic function will be evaluated prior to transplant. 
• The patient will also undergo a pregnancy test if applicable.
• Other tests include ferritin, ABO blood type, CBC with differential, coagulation studies and quantitative immunoglobulins.
• Many of the chemotherapy medications utilized in the conditioning stage (such as busulfan) require close monitoring after the infusion is complete.
• Pulmonary function test (PFT) to determine a baseline.
• CT scan to evaluate the extent of disease.
• PET scan shows how the organs and tissues of the body are functioning and can show cellular level metabolism changes of an organ or tissue.
• Cardiac tests include EKG to evaluate heart rhythm and an echocardiogram provides information about heart and valve function.

After transplant:

• Routine lab draws after transplant include CBC and CMP (which includes renal labs and liver enzymes). If the patient is receiving tacrolimus or cyclosporine, those levels will be evaluated routinely as well.
• If infection is suspected, the patient will be “pan cultured.” This means we send every kind of culture we can obtain…blood, urine, wound, central line catheter tip, and sputum.
• Chest X-ray may be utilized in cases when the patient is experiencing respiratory complications, fluid volume overload or suspected pneumonia or pneumonitis.
• Pulmonary function tests (PFTs) are conducted after transplant when respiratory complications are of special risk or the patient exhibits signs of respiratory involvement.

T: What TREATMENTS will be provided? 

Before transplant:

• Patients will receive immunosuppressants to help prevent graft-versus-host disease in allogeneic transplant.
• Chemotherapy 
• Possibly radiation in conjunction with chemotherapy
• Medications to address side effects of chemotherapy and radiation such as antiemetics.

After transplant:

• To prevent GvHD, the patient will receive a medication that lessens the potential for rejection – tacrolimus or cyclosporine. 
• A colony-stimulating factor such as Granix (tbo-filgrastim) may be used to help shorten the time from neutropenia to engraftment and reduce the occurrence of neutropenic fever. 
• Antibiotics will be utilized in cases of infection and may even be used prophylactically. Remember, the patient is neutropenic and immunosuppressed so they are at extremely high risk for infection!
• The patient will be prescribed a neutropenic diet to help prevent infection. This includes no fresh fruits or vegetables and bottled water only.
• The patient may require PRBC and platelet transfusions. If the patient underwent an allogenic transplant, the RBCs must be “washed” prior to administration and may also need to be leukoreduced and CMV negative.
• Specialized treatment aimed at specific complications as needed.

Another key consideration throughout the entire phase of treatment is to prevent infection. The key tenements of infection prevention include: 

• Maintain neutropenic precautions in a private, positive pressure room. All visitors and healthcare workers entering the room should wear the appropriate PPE. Other neutropenic precautions include no fresh flowers/plants in the room, no stagnant water, no ill visitors, no pet visits and the patient must wear a mask when outside the room.
• Ensure everyone entering the room (and the patient) adhere to the strictest protocols for proper hand hygiene.
• Provide excellent oral care (utilize soft brushes or sponges if the patient has mucositis or GvHD).
• If the patient is neutropenic, avoid any trauma to the skin including enemas, IM injections, rectal temps and even Foley catheters and suppositories. 
• Maintain the integrity of central lines by changing dressings per protocol and as needed, scrubbing the hub vigorously with alcohol prior to use, flushing the lines routinely, and changing all IV tubings as scheduled.
• Perform perineal care promptly to prevent UTI.
• Perform catheter care per protocol (at least once per shift) and when soiled to prevent catheter-associated UTI (CAUTI).
• Daily bathing with chlorhexidine (CHG) helps prevent infection. Note that this may be very irritating to the skin of someone with a radiation rash or GvHD so alternative methods of bathing are likely utilized in these cases.
• Preserve skin integrity by keeping the patient clean and dry, and by repositioning the patient as needed to prevent pressure ulcers from developing.

Note that soiled linens/clothing and waste from patients who have recently received chemotherapy needs to be handled with care. This includes the appropriate PPE (chemo gloves or double gloves, gowns, and goggles/face shield if splashing is a potential risk). Dispose of all waste in an appropriate “chemo bin” and double flush the toilet after depositing waste. 

In addition, patients and families may require a fair amount of psychosocial support during BMT. Provide opportunities for therapeutic communication and if the patient does not have a social worker assigned, advocate for a social work consult as well as spiritual care as appropriate. You can also provide resources for community support to patients and their families as these have been shown to decrease anxiety and stress related to bone marrow transplant.

E: How do you EDUCATE the patient/family?

In addition to ensuring the patient and/or their family understand the medications, tests and treatments involved in their care, other things to include in your teaching plan are:

• Infection prevention measures such as hand hygiene, the use of PPE, restriction of ill visitors, and restrictions on what the patient can have in the room (such as fresh flowers).
• Neutropenic diet parameters to follow both in the hospital and at home. It’s probably best if the family avoids bringing in outside food while the patient is in the hospital. Neutropenic diet guidelines include: 
  • No raw or undercooked eggs, fish, shellfish, meats, poultry
  • No deli, processed, cured or smoked meats
  • No salad bars, potlucks, or buffet-style restaurants
  • No leftovers older than 48 hours 
  • The patient may need to avoid most raw fruits and vegetables (sometimes bananas are allowed due to the thick skin on the fruit).
  • Thoroughly wash all produce, even fruits that have thick skins.
  • Practice safe food handling such as keeping a dedicated cutting board for meats. Plastic cutting boards are better than wood cutting boards as these are more difficult to clean and can harbor bacteria. Ensure food is refrigerated or frozen immediately after purchase and that leftovers are refrigerated or frozen within two hours of eating. For an excellent summary of the neutropenic diet, check out this resource from Memorial Sloan Kettering Cancer Center.
  • No unpasteurized products including honey.

In closing, bone marrow transplant is a wonderful procedure that saves lives. Be The Match donor registry has connected more than 111,000 patients with blood stem cell donors. If you would like to get on the Be The Match registry through the National Marrow Donor Program, go to bethematch.org to get started. The process involves a simple cheek swab you can perform at home…then you just sit back and wait to hear if you’ve been matched. And, the good news is, you might just save a life.

Take this topic on the go by tuning in to episode 279 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.

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