Hematology Oncology & Bone Marrow Services

What is Bone Marrow Transplant?

Bone Marrow is the tissue inside the bones, which contains blood forming cells, known as Hematopoietic Stem Cells (HSC). If this Bone Marrow malfunctions due to reasons like cancer (Leukemia), Thalassemia or Immunological causes (Aplastic Anemia) then deficiency of formed components of blood sets in, resulting in weakness, infections and bleeding ultimately leading to death. Bone Marrow or Hematopoietic Stem cell transplant is a procedure in which Diseased Marrow is replaced by Healthy Marrow or Hematopoietic Stem Cells.

Why you need Bone Marrow Transplant?

There are some diseases like Thalassemia, in which conventional treatment options are mainly supportive blood / component transfusions requiring multiple blood donors and frequent hospitalization, ultimately resulting in iron overload, organ toxicities, growth failure and viral (HIV, Hepatitis B, Hepatitis C) infections. Allogenic Bone Marrow / Stem cell is the only curative treatment available for these patients. Similarly treatment of Leukemia consisted of Chemotherapy but the allogenic transplant remains the most potent Anti-leukemia Therapy and is a curative option. In leukemia chemotherapy dictum is higher the dose, better the disease control. Very high doses of Chemotherapy cannot be given due to lethal toxicity of Bone Marrow failure. During transplant a very high dose of Chemotherapy is given to eradicate the diseased Bone Marrow but it is followed by infusion of donor’s hematopoietic stem cells (allogenic transplant) or patients own pre-collected stem cells (Autologous) to restore blood production. The effectiveness of transplant depends upon high dose Chemotherapy given and graft versus Leukemia / Lymphoma effect, which is seen in allogenic transplant in which donors stem cell destroys cancer cells which escapes killing by Chemotherapy. With advancements in learning and refining of conditioning regimen, including reduction of doses of chemotherapy and more reliance on graft vs tumor effect, the benefits of transplant have been extended to elderly population as well.

Sources of hematopoietic stem cells

• Bone Marrow: Stem cells from Bone Marrow are collected by using aspiration needles from the iliac crest (hip bone). It is carried out under general Anesthesia, is safe and painless, with donor being discharged on next day Bone Marrow stem cells are preferred in diseases like Thalassemia or Aplastic Anemia. With Bone Marrow as a graft source, recovery period is delayed as compared with peripheral blood stem cells but the risk of graft versus host disease is less.
• Peripheral Blood: Stem cells can also be collected from larger veins of body using apheresis technique on a cell separator machine after giving growth factor injections for 4-5 days. It is a very safe and reliable procedure taking only a few hours and does not require Anesthesia. Stem cells can be collected even difficult to mobilize patients with plerixafor and G CSF support. In comparison to Bone Marrow graft, the recovery is earlier by 5-7 days with peripheral blood stem cell graft. This type of transplant is preferred for Leukemia, Myeloma and Lymphomas.
• Cord Blood: Blood collected from placenta after birth is a rich source of Hematopoietic Stem Cells, can also be used for allogenic stem cell transplants. Problem is low volume and cell dose resulting in delayed recovery / engraftment failure.

Autologous Versus Allogenic Transplant

Autologous Transplant involves using a patient’s own Hematopoietic Stem Cells. It is usually done for multiple Myeloma, Relapsed Hodgkin and Non Hodgkin Lymphoma and T Lymphoma. In this procedure a patient’s stem cells are first collected after achieving at least partial response in disease and then a very high dose of Chemotherapy is given to eradicate existing disease followed by reinfusion of collected stem cells to reestablish blood formation.

In Allogenic Transplant Stem cells are collected from a healthy donor. This healthy donor is usually a sibling (related donor fully matched or haploidentical) or can be found from international donor registry (unrelated donor) or obtained from umbilical cord blood. Voluntary donor registries from India like DATRI are very active and have provided donors for multiple transplants.

Bone Marrow Transplant Procedure

A Transplant Process includes following phases- Stem Cell Collection from donor or patient, Conditioning with chemo-radiotherapy for the patient, stem Cell Infusion, pre-engraftment bone marrow suppression and post engraftment follow up. Average time taken prior to engraftment ranges from 3-4 weeks in the BMT unit. After that patient is discharged home on oral medications to prevent graft versus host disease and infections. Patients need to be in close regular follow up for first 3-6 months of transplant and advised to stay near the transplant centre. By one year post transplant, patient’s immune system recovers and most of the medicines can be stopped.

• Stem Cell Collection: Stem Cells are collected from donors’ blood (in allogeneic transplant) by cell separator machine or Bone Marrow aspiration. In Autologous transplant Stem Cells are collected by cell separator machine from patients own blood. Hence, it can be done only after disease has been brought under control by using standard treatment.
• Conditioning: Conditioning is the name given to high dose Chemotherapy or Radiotherapy to destroy or suppress patients existing Bone Marrow and provide immunosuppresion so that donor Stem Cell can home in Bone Marrow and start functioning. Drugs used in conditioning differs by the underlying condition for which transplant is being done.
• Stem Cell Infusion & Engraftment: After conditioning Blood Stem Cells or Bone Marrow are given to the patient through veins, just like Blood Transfusion. These stem cells then reach to Bone Marrow, home there and start producing blood cells. Time taken for blood production is called engraftment period. Before engraftment patient’s blood counts are markedly depressed for around 10-20 days, chances of infections are highs so patients are kept in strict isolation and hepa-filtered rooms. During this time patient will need close monitoring of blood counts and regular blood/platelet transfusions.

Side Effects

Side effects of transplant are due to Chemotherapy / Radiotherapy used in conditioning which is seen both in Autologous and Allogenic Transplants or Immunological Reaction known as graft versus host disease seen in Allogenic Transplants.

Nausea, Vomiting, Loss of Appetite – Usually it is for short period, lasting for few days. With the availability of modern drugs it can be prevented and controlled to great extent.

Mouth Ulcers – Usually mild, lasting for few days and not requires specific treatment other than pain control. Sometimes it can be severe enough to forbid drinking / swallowing, in that case patients are given nutrition through veins.

Hair Loss – High dose chemotherapy / radiotherapy used in conditioning results in universal hair loss but it is temporary as hairs come back within few months after transplant.

Fever – Patients are prone to infections due to markedly low white blood cell counts before engraftment. To prevent infections patient are kept in strict isolation rooms with filtered air till their blood counts improve.

Bleeding – Platelets are the blood component which prevents bleeding and their count decreased after conditioning, resulting in risk of bleeding in skin, mouth, nose or other sites. To prevent bleeding, platelets are transfused to maintain an acceptable platelet count. Once engraftment occurs, the platelet production starts and bleeding risk disappears.

Fertility – Temporary or permanent sterility may occur in almost all adult / adolescent male and female patients after transplant due to side effects of chemotherapy / radiotherapy although ability to have sex is not affected by transplant. It is advisable for males patients, who plan to have family to have their sperm stored for future use.

Graft Versus Host Disease – Once engraftment occurs, one side effect which is seen in Allogenic Transplant is Graft Versus Host Disease (GVHD). It refers to reaction mounted by donor’s blood cell to patient’s body. It occurs in spite of patient and donor being HLA matched hence medicines are given to prevent it from occurring. It is usually mild, affects skin (rashes), liver (jaundice) or intestines (loose motions, pain abdomen) but can be serious and life threatening in a fraction of patients. Once GVHD occurs, it does not mean that transplant has failed. This can be treated with immunosuppressive therapies with good results.

Relapse – Even though transplant is performed with curative intent, some patients with very aggressive disease may relapse. The risk of relapse decreases significantly after 2 years post transplant. Monitoring the patient regularly for relapse and early intervention with chemotherapy, decreasing immune suppression or donor lymphocyte infusion can be used to salvage relapse in many patients.