Is bone marrow transplantation a cure for lymphoma and other blood cancers?

Before treating cancer, doctors withdraw a portion of bone marrow tissue rich in stem cells and re-inject into the patient later. Alternatively, stem cells may be retrieved from a donor or umbilical cord blood. Once injected, bone marrow cells find their way back into bone marrow. These cells then make new blood cells that are cancer free. With BMT after anticancer treatment, the stem cells divide into new, healthy blood cells and thus, the blood is cancer-free.

At a Glance:

What are cancers of blood?

Cancers that originate in the blood cells are referred to as “liquid tumors” or “blood cancers”. Cancer involves the bone marrow, blood cells, and the lymphatic system. The bone marrow helps regulate clotting, build bone and cartilage, blood cells regulate the flow of oxygen and carbon dioxide and the lymphatic system carries lymphatic fluid that is responsible for fighting infections, in presence of white blood cells. Most cancers on the other hand that develop within the human body are solid cancers as they originate as a solid lump of abnormal cells that grow rapidly.

What are the different types of blood cancers?

Leukemia, lymphoma and myeloma are three major types of blood cancers. The three liquid tumors affect the blood-forming organs. They arise due to a genetic mutation of immature blood cells. They do not form solid tumors and are also known as hematopoietic neoplasms.

Though the liquid tumors have similarities they show an ample range of difference based on the location of cancer, appearance and progression of the disease.

Leukemia: Occurs in the blood and bone marrow. It affects the white blood cells that fight infections. Based on the type of white blood cells affected and the progression of the disease, leukemia is classified either on the basis of the type of white blood cell involved i.e

• Lymphoblastic leukemia- affecting the lymphocytes
• Myeloid leukemia- affecting the myelocytes

Or on the basis of the speed of progression

• Acute leukemia- the progression of the disease is rapid and occurs suddenly
• Chronic leukemia-progression is slow and occurs over months to years

Myeloma: It is the disorder of the plasma cells i.e mature lymphocytes that fight infection by antibodies or immunoglobulins which is the protein responsible for immunity. The cancer cells surround the bone marrow and prevent it from producing normal cells, such as the red blood cells, white blood cells, and platelets. It is also known as multiple myeloma, as it may affect more than one site in the bone marrow.

What is lymphoma? Where does lymphoma originate?

Lymphoma– cancer occurs in the lymphatic system which affects the abnormal growth of immature lymphocytes that are unable to protect the body against infection. Lymphoma can be classified into

• Chronic lymphocytic leukemia
• Cutaneous B-cell lymphoma
• Cutaneous T-cell lymphoma
• Waldenstrom macroglobulinemia
• Non-Hodgkin’s lymphoma (NHL)
• Hodgkin’s lymphoma – earlier known as Hodgkin’s disease, it is less common than NHL and affects the lymphatic system of the body. There are two types of Hodgkin’s lymphoma
• Classical Hodgkin’s lymphoma
• Nodular lymphocyte

Lymphoma is a cancer of the lymphatic system, which comprises of the structures like the lymph nodes, spleen, thymus, bone marrow and vessels that carry the lymph fluid throughout the body. The lymphatic fluid contains white blood cells that are responsible for protection against infection and lymph nodes capture bacteria and viruses from spreading in the body.

Lymphoma originates in the lymphocytes (white blood cells). In lymphoma, there is an abnormal, rapid growth of immature lymphocytes. Due to uncontrolled growth of the immature cells, they are unable to perform the action of germ/infection-fighting.

What is Non-Hodgkin’s Lymphoma, what are its types?

Non-Hodgkin’s lymphoma (NHL) is the most common type of lymphoma, accounting for nearly 90% of lymphomas. NHL causes white blood cells to grow abnormally. Based on the type of white blood cell the cancer is affecting, NHL is classified as:

• B-cell Lymphoma
• T-cell Lymphoma
• Mantle cell Lymphoma
• Small Lymphocytic Lymphoma- Found mostly in lymph nodes

What are the causes of blood cancers & lymphoma?

It is not very clear how lymphoma is caused, but researchers associate cancer with few risk factors such as:

• Age: Young adults between the ages of 20 to 30 years are more prone to lymphoma.
• Exposure to harmful radiation and chemicals: Prolonged exposure to agents like pesticides, fertilizers, herbicides and nuclear radiation increases the risk of lymphoma.
• Family history: A person with a parent or grandparent suffering from lymphoma has a higher risk of developing the cancer
• Gender: Men are at a  higher risk than women
• Immuno–compromised state: People suffering from immunodeficiency diseases, or those undergoing some treatment with immune-suppressant drugs are at greater risk of developing lymphoma

What are the symptoms of lymphoma?

Cancers of the blood can have similar symptoms despite of them being different diseases. Some of the symptoms experienced by a person with Lymphoma include:

• Night sweats
• Painless swelling of lymph nodes in the area of groin, neck and armpits
• Persistent fatigue
• Shortness of breath without exertion
• Unexplained fever
• Unintended weight loss

How is blood cancers diagnosed?

In case of any visible sign or symptom, consult a physician who may refer you to hematologist or hemato-oncologist. Diagnosis is usually made by the doctor on the basis of:

• Medical History
• Physical examination
• Tests as required
  • Biopsies such as lymph node biopsy and bone marrow biopsy
  • Blood tests and cell counts
  • Imaging tests like
    • Computerized tomography (CT) scan
    • Magnetic Resonance tomography (MRI)
    • Positron Emission tomography (PET) scan

What are the treatment options for blood cancers & lymphoma?

The treatment options for blood cancers & lymphoma are based on the type and stage of cancer and other factors like overall health, age, and sensitivity to certain medications. Some of the treatment options that may be used in combination include:

• Bone Marrow Transplant (BMT): Also known as stem cell transplant.
• Radiation therapy: Use of high-powered energy beams to destroy cancer cells.
• Chemotherapy: Use of drugs to destroy cancer cells
• Palliative care: Intended to improve the quality of life of patients in advanced stages of cancer or those who may not be amenable to treatment.

What is Bone Marrow Transplant, is it recommended for all blood cancers?

Bone marrow transplant is a procedure wherein the normal stem cells from the bone marrow are taken, filtered and administered to the patient. It is a special therapy used for patients with certain cancers such as lymphoma, leukemia and myeloma or other blood diseases such as aplastic anemia and sickle cell anemia. Healthy bone marrow stem cells from the person’s own body or those from a matched donor are infused within the bloodstream from where they reach the bones to rebuild renewed bone marrow. Bone marrow is a spongy structure inside the bones that contains stem cells. These stem cells generate different types of blood cells such as red blood cells, white blood cells, and platelets.

Bone marrow transplant can be used to treat leukemia, lymphoma and myeloma; however, it may not be always the recommended option. Since bone marrow transplant is carried out after a very high dose of chemotherapy or radiotherapy, there may be risks and complications out of bone marrow transplant that can even be fatal and life-threatening. Hence, case selection for transplant may depend on various factors like:

• Availability of matching donor  
• Diagnosis
• General physical condition
• Response to earlier treatments
• Stage of disease

What are the types of Bone marrow transplant?

Based on where the stem cells are taken from, bone marrow transplant are of three types;

• Autologous stem cell transplant: The stem cells are taken from the bone marrow of the patient itself.
• Allogenic stem cell transplant: The stem cells are infused from another person i.e. a donor. There should be a match in stem cells between a recipient and a donor. In most of the cases, the donor may be related to the recipient. Sometimes the donor maybe unrelated to the person receiving the bone marrow. In such a case, the procedure is called matched, unrelated donor (MUD) transplant.
• Umbilical cord blood transplant: The stem cells are taken from the umbilical cord of a new born baby, frozen and stored until required. The stem cells are still immature; therefore, there is not much of a need for the donor and the recipient to have a perfect bone-marrow match.

What to expect before and after a bone marrow transplant?

Before the bone marrow transplantation, tests are carried out and conditioning process will take place where cancer cells are destroyed and the body is prepared to receive new stem cells. After the conditioning process, the bone marrow is then infused into the bloodstream using a central line, where they begin to develop new healthy stem cells. The patient is monitored for several days or even months to check on the condition and stability of the body. Few complications such as nausea and diarrhea after the transplant or those related to chemotherapy can be expected that can be managed by relevant medications.

What are the steps involved in a bone marrow transplant?

Preparation: Before a patient undergoes bone marrow transplantation, a series of tests may be conducted to determine the status of the patient’s health. To assess whether or not the donor cells will match with those of the recipient, the donor’s blood is tested by a procedure called human leukocyte antigen testing (HLA testing).

• Finding a match: The success of the transplant depends largely on the right donor. Better HLA matching allows reduced risk for graft rejection and GVHD. If the patient has no matching relative, specialists search donor registries to find a volunteering match. If there is no match, patients may use cord blood stem cells which don’t need to be closely matched.

Stem cell collection:

• Circulating or peripheral blood: Donors receive an injection to make and release more stem cells than normal. After a certain period, the donor’s blood is collected and sifted for stem cells using an apheresis machine. The remaining blood is given back to the donor. The cells collected can be used immediately or frozen for future.
• Bone marrow: A specified amount of bone marrow that the body replaces every month is drawn out of the pelvic bones and with a needle.
• Umbilical cord blood: The stem cell from an umbilical cord of a new born baby is collected, frozen and stored until required for transplantation.

Pre-transplant conditioning: In patients being treated for cancers (lymphoma and blood cancers), before the commencement of bone marrow transplantation, the patient is subjected to undergo chemotherapy with or without radiotherapy.

Stem cell infusion: A few days after conditioning, patients receive an intravenous infusion of stem cells. These cells travel in blood and settle in the bone marrow. The infusion may take a few minutes or a few hours based on the volume of stem cells being delivered.

Engraftment: The donated cells root themselves in the bone marrow and begin producing blood cells that are cancer-free. It takes around 10 days to several weeks for the successful engraftment and new blood cell production.

Recovery: The patient undergoes stringent follow-ups for the next 100 days on a daily or weekly basis in order to control infections and other complications. Also, it takes almost a year for the blood count to normalize and the new immune system to work well.  

What is conditioning in bone marrow transplant procedure?

Pre-transplant conditioning is a preparative phase where the patient is treated for complete eradication of cancer by means of chemotherapy. This conditioning process is done to destroy cancer cells and to reduce the immunity for better compatibility with new stem cells to be transplanted. The reduced immunity ensures that the recipient’s body doesn’t attack the donor cells as foreign body. The use of chemotherapy or radiation as conditioning therapy is based on the health condition of the patient and the type of transplant to be conducted. This preparative phase leaves the patient highly vulnerable to infections. In some cases, the patients undergo a reduced intensity regimen.

What are the risks and survival rate after bone marrow transplant?

There are few precautions that need to be taken before a bone marrow transplant is carried out. The health status of the patient needs to be monitored, in case the bone marrow is taken from another person, certain tests are to be conducted to ensure that there is a match in the bone marrow of a donor and a recipient.

Some other complications or risks that can arise from a bone marrow transplant include;

• Graft failure
• Infections
• Recurrence of the cancer
• Organ failure
• Death

The patient is at highest risk within 100 days of transplant. One year survival rate after bone marrow transplant is 62%, as per Memorial Sloan Kettering Cancer Center, as of March 2012. With advancements in transplant technology, there has been a higher success rate in bone marrow transplant over the years.

What is graft versus host disease?

Graft versus host disease (GVHD) is a complication after a bone marrow transplant. It usually occurs in an allogeneic stem cell transplant, where the donor’s stem cells recognize the host’s tissues as a foreign entity and attack them. GVHD can occur any time after stem cell transplantation. Acute GVHD occurs after the first month of transplantation and chronic GVHD occurs develops very much later after transplantation.

What are the outcomes of a bone marrow transplant, can cancer relapse or recur?

The bone marrow transplant is considered to be a procedure with a good success rate over the years. For some blood cancers, there has been a success rate as high as 85%. Older age is a poor prognostic factor for survival after a bone marrow transplant. The outcomes of a bone marrow transplant vary from person to person, some show very fewer side effects of bone marrow transplantation; on the other hand, some patients may show numerous complications.

The higher production of lymphocytes reduces the chances of recurrence of lymphoma after stem cell transplantation. Studies have shown that bone marrow transplantation in patients above 45 years of age shows a greater risk of relapse.

What are the precautions necessary after a bone marrow transplant?  

It may take several months for a body to regain energy and adapt with new stem cells. Therefore, few precautionary steps are necessary after a bone marrow transplant:

• Avoid exposure to surroundings that may lead to infections for at least a year after transplantation. This includes wearing a mask, frequent hand washing, avoiding crowded places, etc.
• Gain as much information as possible on lymphoma and on bone marrow transplantation, be aware of your own body to notice and report any abnormal symptoms on time.
• Have a safe, healthy and nutritious diet, including drinking water.
• Personal hygiene and oral care: Maintain personal hygiene, brush your teeth at least twice a day and keep your mouth bacteria free.

Conclusion:

Incidence of blood cancer or liquid tumour has been increasing over the years in various age groups. Lymphoma, a type of blood cancer compromises the immune-system of the body, reduces the oxygen regulation as well as clotting factor of the body. Various treatment plans have shown promising outcomes with bone marrow transplant showing a good success rate. However, precautionary measures are equally important in preventing risks and complications of bone marrow transplant.  

We hope we were able to address your queries related to Lymphoma. If you wish to know more about lymphoma and its treatment, you can request for a call back and our experts will call you and answer all your queries.

References:

• Medline Plus. Lymphoma. Available at: https://medlineplus.gov/lymphoma.html#cat_92.  Accessed on 16^th October 2018.
• MayoClinic. Lymphoma. Available at: https://www.mayoclinic.org/diseases-conditions/lymphoma/diagnosis-treatment/drc-20352642. Accessed on 16^th October 2018.
• Cancer Council. Leukaemia. Available at: https://www.cancer.org.au/about-cancer/types-of-cancer/lymphoma.html. Accessed on 16^th October 2018.
• Leukaemia Foundation. What is Myeloma?. Available at:  https://www.leukaemia.org.au/disease-information/myeloma/. Accessed on 16^th October 2018.
• Myeloma UK. What is Myeloma? Available at: https://www.myeloma.org.uk/understanding-myeloma/what-is-myeloma/. Accessed on 16^th October 2018.
• Cancer.gov. Leukemia, Lymphoma, and Multiple Myeloma: Toward a New understanding. Available at: https://www.cancer.gov/about-nci/legislative/hearings/2001-leukemia-lymphoma-multiple-myeloma-new-understanding.pdf. Accessed on 17^th October 2018.
• Medline Plus. Bone marrow transplant. Available at: https://www.cancer.gov/about-nci/legislative/hearings/2001-leukemia-lymphoma-multiple-myeloma-new-understanding.pdf. Accessed on 17^th October 2018.
• Seattle Cancer Care Alliance. Bone Marrow Transplant Facts. Available at: https://www.seattlecca.org/treatments/bone-marrow-transplant/bone-marrow-transplant-facts-0. Accessed on 17^th October 2018.
• MayoClinic. Bone Marrow Transplant. Available at: https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/about/pac-20384854. Accessed on 17^th October 2018.
• Memorial Sloan Kettering Cancer Center. MSK’s One-Year Survival Rate after Allogeneic Bone Marrow Transplant Exceeds Expectations. Available at: https://www.mskcc.org/blog/msk-s-one-year-survival-rate-after-allogeneic-bone-marrow-transplant-exceeds-expectations. Accessed on 18^th October 2018.
• US National Library of Medicine National Institute of Health. Bone marrow transplantation in patients aged 45 years and older. Available at: https://www.ncbi.nlm.nih.gov/pubmed/3511986. Accessed on 18^th October 2018.
• Medline Plus. Bone Marrow Transplant- discharge. Available at: https://medlineplus.gov/ency/patientinstructions/000010.htm. Accessed on 18^th October 2018.

About Author –

Dr. Ganesh Jaishetwar, Consultant Hematologist, Hemato-Oncologist & Bone Marrow Transplant Physician

MD, DM (Clinical Hematology), BMT, TMC, FACP, Fellow in Bone Marrow Transplantation (Canada)

Dr. Ganesh Jaishetwar has successfully completed more than 60 blood & bone marrow transplants at Yashoda Hospitals. His expertise and special interests include treatment for Blood cancers (Leukemia, Lymphoma & Multiple Myeloma, MDS, Myeloproliferative disorders), blood disorders (Anemia, Thallasemia, Aplastic anemia etc.), immunodeficiency disorders.