The Risk of Neutropenia Due to Bone Marrow Replacement

Introduction:

A bone marrow transplant is a process that introduces healthy blood-forming stem cells into the body. A bone marrow transplant replaces damaged stem cells with healthy cells. A bone marrow transplant is required if the bone marrow stops working and does not produce enough healthy blood cells.

What Is a Bone Marrow Transplant or Replacement?

Bone marrow is a spongy, fatty tissue inside the bones. It produces red blood cells (RBCs carry oxygen and nutrients to the body), white blood cells, and platelets (help form blood clots). Bone marrow contains immature blood-forming stem cells called hematopoietic precursor cells. These cells are differentiated and can only make copies of themselves. However, these stem cells are unspecialized and immature. These cells can multiply through cell division which will remain as stem cells or differentiate and mature into many blood cells. The hematopoietic precursor cells in the bone marrow will make new blood cells throughout the lifespan.

Healthy stem cells are from a donor or can come from their own body. Stem cells can be harvested or grown before chemotherapy or radiation treatment. Those healthy cells are then stored and used in transplantation. Bone marrow transplants use cells from their own body (autologous transplant) or a donor, called an allogeneic transplant.

What Are the Types of Bone Marrow Transplants?

1. Allogenic stem cell transplant (uses healthy stem cells from a donor to replace the bone marrow).

2. Autologous stem cell transplant.

What Are the Uses of Bone Marrow Transplants?

A bone marrow transplant is used to:

• Replace bone marrow with new stem cells.

• Provide new stem cells that can help kill cancer cells directly and produce new blood cells to resume normal functions of the body.

Bone marrow transplant is a procedure for the following conditions:

• Acute leukemia (a type of cancer of blood and bone marrow that affects white blood cells).

• Aplastic anemia (a condition in which the body stops producing enough new blood cells).

• Bone marrow failure syndromes.

• Chronic leukemia.

• Hodgkin's lymphoma (cancer of the lymphatic system).

• Immune deficiencies.

• Multiple myeloma (a cancer of plasma cells).

• Neuroblastoma.

• Non-Hodgkin's lymphoma.

• Plasma cell disorders.

People with bone marrow transplants may experience minimal problems or may lead to serious complications requiring treatment or hospitalization. The complications can be life-threatening.

Possible complications from a bone marrow transplant include:

• Graft-versus-host disease (a complication that occurs in allogeneic transplants only).

• Stem cell (graft) failure.

• Organ damage.

• Infections.

• Infertility.

• Death.

What Is Graft-Versus-Host Disease?

A potential risk occurs when stem cells come from donors. A transplant that uses stem cells from an allogenic transplant causes a risk of developing graft-versus-host disease (GVHD). It occurs when the donor stem cells that make up new immune cells see the body's tissues and organs as foreign and attack them. Acute GVHD happens during the first months after the transplant. It typically affects the skin, digestive tract, and liver. Chronic GVHD develops later and can affect many organs. GVHD may happen at any time after the transplant. People with have an allogeneic transplant get GVHD. The risk of GVHD is higher if the precursor is derived from an unrelated donor. GVHD happens to anyone who has a bone marrow transplant from the donor.

The two kinds of GVHD are acute and chronic GVHD. Chronic GVHD signs and symptoms include:

• Joint or muscle pain.

• Shortness of breath.

• Persistent cough.

• Dry eyes and blurred vision.

• Skin changes.

• Rash.

• Dry mouth.

• Mouth sores.

• Diarrhea.

• Nausea.

• Vomiting.

What Is Neutropenia?

Neutropenia is a condition characterized by low levels of neutrophils. They are white blood cells that protect the body from infection. It increases the risk of many infections.

What Are the Types of Neutropenia?

The four types of neutropenia are:

Congenital:

• Congenital neutropenia occurs at birth. Neutropenia causes very low neutrophil levels and, in some cases, a complete lack of neutrophils. This causes serious infections in infants and young children.

• Cyclic neutropenia is present at birth.

• Neutrophil counts vary in a 21 day cycle.

• A period of neutropenia lasts a few days, followed by normal levels for the rest of the cycle. The cycle begins again.

Autoimmune:

• With autoimmune neutropenia, the body makes antibodies that fight neutrophils. These antibodies kill the neutrophils, causing neutropenia.

Idiopathic:

• This neutropenia develops at any time in life and can affect anyone. The cause is unknown.

What Are the Symptoms of Neutropenia?

The symptoms are mild to severe. The symptoms are very severe when the neutrophils are very less. Typical symptoms include fever, pneumonia, gum infection, or inflammation. Severe congenital neutropenia causes serious symptoms. It often includes bacterial infections. Bacterial infections grow on the skin, respiratory tract, and digestive tract.

What Causes Neutropenia?

The following factors can trigger neutropenia:

• Chemotherapy.

• Radiation therapy.

• Certain drugs.

• Conditions that affect the bone marrow.

• Severe aplastic anemia.

How Can Graft Failure Cause Neutropenia?

• Graft failure is extremely unusual in autologous stem cell transplantation. Graft failure occurs when the bone marrow does not function well.

• The graft may fail to grow in the patient resulting in bone marrow failure with the absence of red blood cells, white blood cells, and platelet production.

• This results in infection, anemia, and bleeding. Graft failure may also occur in patients with extensive marrow fibrosis before transplantation, a viral illness, or from the use of some drugs (such as Methotrexate).

• In leukemia patients, graft failure is often associated with cancer recurrence; the leukemic cells may inhibit the growth of the transplanted cells.

• In some cases, the reasons for graft failure are unknown. The body makes enough white blood cells, platelets, or red blood cells to avoid infections, bleeding disorders, or anemia. But the bone marrow stops working and does not produce enough healthy blood cells.

• Stem cells can be harvested or grown before they are infused into the donor. Graft failure occurs when the patient results in bone marrow failure with the absence of red blood cells, white blood cells, and platelet production. This results in infection, anemia, and bleeding.

• Graft failure may also occur in patients with extensive marrow fibrosis before transplantation, a viral illness, or from the use of some drugs (such as Methotrexate).

• In leukemia patients (cancer of white blood cells), graft failure in the leukemic cells may inhibit the growth of the transplanted cells.

• Unexpected neutropenia after bone marrow transplantation can be caused by graft rejection.

• Thrombocytopenia is a condition that causes low platelet count and anemia (low hemoglobin or red cell count) that leads to nonfunctional bone marrow.

• Thrombocytopenia causes bleeding in the gastrointestinal (GI) tract, brain, lungs, and other body parts.

• Anemia causes fatigue, lack of appetite, irritability, rapid heart rate, and other symptoms.

• The infused bone marrow may fail to produce blood cells for the host's body.

• This complication is called graft failure. It occurs because of infection, recurrent disease, or if the stem cell count of the donated marrow is insufficient to cause engraftment.

• It is treated by giving a second infusion. In this case, the infused stem cells may be from a different donor and a different source than was used for the first infusion.

Conclusion:

Graft rejections can cause serious problems in the body that lead to a collapse in total blood count. Graft failure is treated with another transplant, including a conditioning regimen and an infusion of bone marrow or blood stem cells. During the period between the destruction of the old bone marrow and the production of new blood cells by the transplanted stem cells, the patient may experience neutropenia. Bone marrow replacement can cause neutropenia as a side effect due to the destruction of existing bone marrow and the time it takes for transplanted stem cells to begin producing new blood cells.