Bone Marrow Transplant ( BMT)

Conditions that can be treated by BMT/HSCT

Haematological Malignant conditions:

• Acute Lymphoblastic leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Chronic Myeloid Leukemia (CML)
• Hodgkin Lymphoma
• Non-Hodgkin Lymphoma
• Myelodysplastic syndrome (MDS)
• Multiple Myeloma
• Neuroblastoma
• Germ cell tumors

Benign Conditions : 

• Haemoglobinopathies  like Thalassemia
• sickle cell anemia
• Severe Aplastic anemia
• Primary /Congenital Immunodeficiency syndromes

Autoimmune Disorders : 

Multiple Sclerosis 

Sjogren’s Syndrome

Systemic Sclerosis

Types of Bone Marrow Transplant (BMT)

There are two basic types of transplants, allogeneic and autologous, depending on who donates the bone marrow or stem cells.

Autologous Bone Marrow Transplant: 

Donor and Recipient are same individuals, which means the patients own stem cells are used for the Transplant.  The procedure involves giving high dose chemotherapy to patient in order to remove primary disease. Thereafter, an autologous transplant is conducted to rescue damaged bone marrow. This type of transplant has minimal complication and is preferred for diseases like multiple myeloma and  lymphoma.

Allogeneic Bone Marrow Transplant:  

Donor and Recipient are two separate individuals and transplant is done using the stem cells of donor. It may be-

• Matched  Related, where donor is HLA matched relative usually a sibling.
• Matched Unrelated, where donor is not a relative of patient and usually found from one of the various national or international registries.
• Partially Matched Related, where donor is from a patient’s family but partially matched (haploidentical)

The Procedure : 

Preparation of the Patient : 

• A complete medical history and physical exam are performed, including multiple tests to evaluate the patient’s  conditions and co morbidities like Diabetes, High BP, Renal Function , Liver Function Etc. 
• The Patient will normally be admitted before one week  for hydration, evaluation, and if necessary placement of the central venous line. Blood products and medicines will be given through the catheter during treatment.

Preparation for the donor

• Donor sources available include: self, sibling, parent or relative, nonrelated person, or umbilical cord from a relative. Unrelated Donors may be selected and available from National Registries – in INDIA   DATRI, Chennai ,Jeevan Blood Bank , Chennai ,MDRI (Marrow Donor Registry India), Mumbai,, GENE BANDHU (Bharat Stem Cells), New Delhi ,SCRI-BMST (Bangalore Medical Services Trust), Bangalore , etc. 
• Once a matched donor is found he will be evaluated for General health, infections and full evaluation by the transplant team. In the past the Bone Marrow from the Donor was collected from the Hip bones. At present the stem cells are collected by a process called Apheresis , which is almost similar to Blood Donation and carries much less risk to the Donor. 

Infusion : 

            The collected stem cells are infused  to the patient either through a Central line or through a peripheral vein. 

During infusion of bone marrow, the patient may experience the following:

• Pain
• Chills and Fever

After infusion, the patient may:

• Spend about a month or more  in the hospital
• Be very susceptible to infection
• Need blood transfusions
• Take multiple prophylactic  Medications for Bacterial, Fungal and Viral Infections. 
• Undergo continual laboratory testing
• Experience nausea, vomiting, diarrhea, mouth sores, and extreme weakness
• Experience temporary mental confusion and emotional or psychological distress

Engraftment : 

Engraftment is the process in which the infused stem cells start replacing the patients own cells and grow  into various Blood cells – WBCs, RBS, and Platelets. This may take about 14 to 28 days . 

After the engraftment  the patient may be transferred to a regular ward, or may be discharged if he is considered fit by the Tranplant Physician.  The patient will have to come to the Hospital for regular follow up for identification and treatment of any Long term Complications. 

The  Bone Marrow Transplant Team at KMH : 

BMT Physicians : 

Dr.Margaret Chellaraj  MD DM , Former HOD of Hematology and BMT Physician , Madras    

                                                                    Medical College and RGGGH

Dr. Steve Joseph      MD DM ( Clinical Hematology – AIIMS – Delhi)

Dr. Dharani Jayaraman  MD FNB ( Paediatric Hemato Oncology)

Dr. Meena Sankaran MD FNB Paediatric Hemato Oncology

Transfusion Medicine :

Dr. Anuraga S.  MD ( Transfusion Medicine ) Fellowship in Hematology , CMC, Vellore

Pathologists and Laboratory Medicine :

Dr. SreeGayathri  MD , Fellowship In Lab Hematology, CMC , Vellore. Pathologist and Flowcytometrist 

Dr.Sp.Ganesan  MBBS DCP Clinical Pathologist 

Microbiology and Infectious Disease :

Dr. Keerthi MD Microbiology

Dr. Rajkumar   MD – Infectiuos Disease  Consultant 

Dr. Lokeshwari  MD Microbiologist

BMT Coordinator and Counsellor : 

Mrs.Vijayalakshmi 

Mrs. Hema Chithra 

BMT Nurses : 

Mrs. Nithya ( BMT &Infection Controle Nurse)

Mrs. Malini 

Mrs. Sumathy

Mrs. Thamthi

Complications : 

1 Neutropenic Sepsis: This complication occurs in almost all HCT recipients, and institutional policy should be in place for empirical antimicrobial therapy of bacterial and fungal infections, based on local sensitivity and resistance patterns. All personnel should adhere to hospital infection control policies to prevent and reduce infections in transplant patients.

2. Bleeding: Most patients develop bleeding with a platelet count of less than 10-20 x 109/L.

     A hospital transfusion policy should be in place to prevent management bleeding episodes. 

 3. Mucositis and Nutrition: High dose chemotherapy with or without total body irradiation leads to grade III or IV mucositis in over half of the patients undergoing transplantation. Supportive care in the form of enteral or parenteral nutrition and pain relief by the use of opioids should be considered. 

4. Dyselectrolytemia: Hypokalemia, hypocalcemia, and hypomagnesemia are common causes of dyselectrolytemia in the transplant setting. These abnormalities need to be aggressively corrected. 

5.Engraftment syndrome: Is defined as fever of a non-infectious origin, which develops when white cell count increases post transplant. Classical features include fever >38.30 C, skin rash, non cardiogenic pulmonary edema or hypoxia, or a sudden increase in CRP values >20mg/dL. Treatment includes stopping G-CSF and administration of a short course of steroids.

6.Sinusoidal Obstruction Syndrome (SOS) or Veno-occlusive disease (VOD): SOS is characterized by jaundice, fluid retention, and tender hepatomegaly appearing in the first 35-40 days after HCT. Treatment includes liberal use of diuretics, restriction of fluids and defibrotide.

7. Acute Graft vs Host Disease (aGvHD): This is the most dreaded complication of allogeneic transplantation. It is characterized by damage to skin, liver, or gut leading to skin rash, jaundice, or diarrhea. The initial classification by Glucksberg et  was later modified by Przepiorka et al. Early intervention with the use of corticosteroids leads to the resolution of signs and symptoms in approximately 50% of patients. Institutional policy to treat steroid refractory GvHD should be in place.

8.Graft Failure: is an infrequent but often fatal complication of HCT seen in <5% of autologous, matched related and unrelated donor transplants. The incidence increases to 10% or more in haploidentical and CB transplantation, and its etiology is multifactorial. The key is to take preventive measures following the early identification of risk factors. 

9.Hemorrhagic cystitis (HC): Post-transplant can be categorized according to the time of occurrence as early or late-onset. Early onset typically occurs within 48 hours of completion of 

chemotherapy and is due to the direct toxic effect of drug metabolites and radiotherapy on bladder mucosa. Late-onset HC usually starts after neutrophil engraftment and can occur several months post HCT. This is generally due to the reactivation of BK or adenovirus. Clinical diagnosis is based on the presence of signs and symptoms of cystitis. Supportive treatment includes maintaining adequate hydration, and bladder irrigation may be required in severe cases. Cidofovir may be useful in some patients with BK and adenoviral hemorrhagic cystitis, although the efficacy is uncertain. 

10. CMV reactivation: With the growing number of alternative donor transplants and shift of emphasis from myeloablative to immuneablative strategies, post transplant CMV reactivation has emerged as an important complication. The intent of the physician should always be to treat CMV reactivation and prevent progression to CMV disease. The drug of choice for management of CMV reactivation is ganciclovir/valganciclovir, however if the In ganciclovir non-responsive cases, foscarnet or cidofovir can be used as add on therapy as per institutional protocols.