Bone Marrow Transplant – Indications, Contraindications

Bone Marrow Transplant (hematopoietic stem cell transplant) (HPSCT) involves the administration of healthy hematopoietic stem cells in patients with dysfunctional or depleted bone marrow. This helps to augment bone marrow function and allows, depending on the disease being treated, to either destroy tumor cells with malignancy or to generate functional cells that can replace the dysfunctional ones in cases like immune deficiency syndromes, hemoglobinopathies, and other diseases.

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It may be autologous (the patient’s own stem cells are used), allogeneic (the stem cells come from a donor), or syngeneic (from an identical twin).[rx][rx] It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.[rx] In these cases, the recipient’s immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.[rx]

Types of Bone Marrow Transplant

There are two major types of bone marrow transplants. The type used will depend on the reason you need a transplant.

Autologous Transplants

  • Autologous transplants involve the use of a person’s own stem cells. They typically involve harvesting your cells before beginning a damaging therapy to cells like chemotherapy or radiation. After the treatment is done, your own cells are returned to your body.
  • Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer. After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make normal blood cells. This is called a rescue transplant.
  • This type of transplant isn’t always available. It can only be used if you have healthy bone marrow. However, it reduces the risk of some serious complications, including GVHD.

Allogeneic Transplants

  • The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor’s genes must at least partly match your genes. Special tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you, yet still match, may be found through national bone marrow registries.
  • Allogeneic transplants are necessary if you have a condition that has damaged your bone marrow cells. However, they have a higher risk of certain complications, such as GVHD. You’ll also probably need to be put onmedications to suppress your immune system so that your body doesn’t attack the new cellsThis can leave you susceptible to illness.
    • Related donor transplant — Typically patients begin by trying to identify a relative to be their donor. Siblings are most likely to be a close match (based on HLA typing).
    • Matched unrelated donor transplant — If you don’t have a relative available who is a match, doctors can search international donor registries for an unrelated donor.
    • Haploidentical transplant — If you have not been able to find a closely matched donor, you may be able to receive stem cells from a donor who is a half-match for you. This option broadens the pool of potential donors. Haploidentical, or half-matched, transplants rely on advances in drug therapies to prevent graft-versus-host disease.
    • Cord blood transplant — Stem cells from donated cord blood don’t need to match you as closely. The immune cells in cord blood are not yet trained to fight foreign invaders, like bacteria, so they’re less likely to interact adversely with your tissues. Normally, a unit of cord blood doesn’t have enough stem cells for a transplant in an adult. But doctors can combine units of cord blood and also greatly expand the number of cells per unit using specialized techniques in the lab.

Umbilical cord blood transplant

  • This is a type of allogeneic transplant. Stem cells are removed from a newborn baby’s umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for perfect matching. Due to the smaller number of stem cells, blood counts take much longer to recover.

Syngeneic (identical twin transplant)

  • Stem cells are donated by an identical twin, which is an ideal donor because of the matching genetic identity between donor and recipient.

Parent-child transplant and haplotype mismatched transplant

  • Cells from a parent, child, brother, or sister are not always a perfect match for a patient’s HLA type, but they are a 50% match. Doctors are using these types of transplants more often, to expand the use of transplantation as an effective cancer treatment.

Before the transplant, chemotherapy, radiation, or both may be given. This may be done in two ways

  • Ablative (myeloablative) treatment  – High-dose chemotherapy, radiation, or both are given to kill any cancer cells. This also kills all healthy bone marrow that remains and allows new stem cells to grow in the bone marrow.
  • Reduced-intensity treatment also called a mini transplant – Lower doses of chemotherapy and radiation are given before a transplant. This allows older people, and those with other health problems to have a transplant.

Pre Procedure of Bone Marrow Transplant

  • Major Histocompatibility Complex (MHC) – The group of genes on the short arm of chromosome 6 (p6) that encodes human leukocyte antigens (HLA) which are considered being highly polymorphic leading to a large difference in the resultant expressed proteins on human cells. They are divided into MHC I and MHC II
  • Human Leukocyte Antigens (HLA) These are the proteins expressed on the cellular surface and play an important role in alloimmunity. HLA can be divided into (HLA-A, B, and C) which are encoded by class I MHC and are expressed on all cell types and present peptides derived from the cytoplasm and are recognized by CD8+ T cells. The other HLA type is classified as (HLA- DP, DQ, and DR) which are encoded by MHC II and can be found on antigen-presenting cells (APCs) and this class is recognized by CD4+ T cells.
  • Syngeneic Bone Marrow Transplantation The donor and the recipient are identical twins. The advantages include no graft versus host disease (GVHD) and no graft failure. However, only a tiny number of transplant patients will have the ability to have an identical twin for transplantation.
  • Autologous Bone Marrow Transplantation – The bone marrow products are collected from the patient and are reinfused after purification methods. The advantages include no GVHD. The disadvantage is that the bone marrow products may contain abnormal cells that can cause relapse in the case of malignancy hence; theoretically, this method cannot be used in all cases of abnormal bone marrow diseases.
  • Allogenic Transplantation The donor is an HLA matched family member, unrelated matched donor or mismatched family donors (haploidentical).
  • Engraftment The process of which infused transplanted hematopoietic stem cells produce mature progeny in the peripheral circulation
  • Preparative Regimen – This is a regimen that comprises high-dose chemotherapy and/or total body irradiation (TBI) which are administered to the recipient prior to stem cell infusion to eliminate the largest number of malignant cells and to allow for immunosuppression in the recipient so that engraftment can occur.

Indications of Bone Marrow Transplant

Indications for stem cell transplantation are as follows:

Malignant (cancerous)

  • Acute myeloid leukemia (AML)
  • Chronic myeloid leukemia (CML)
  • Acute lymphoblastic leukemia (ALL)
  • Hodgkin lymphoma (HL) (relapsed, refractory)
  • Non-Hodgkin lymphoma (NHL) (relapsed, refractory)
  • Neuroblastoma
  • Ewing sarcoma
  • Multiple myeloma
  • Myelodysplastic syndromes
  • Gliomas, other solid tumors

Non-malignant (non-cancerous)

  • Thalassemia
  • Sickle cell anemia
  • Aplastic anemia
  • Fanconi anemia
  • Malignant infantile osteopetrosis
  • Mucopolysaccharidosis
  • Pyruvate kinase deficiency
  • Immune deficiency syndromes
  • Autoimmune diseases[rx]

Malignant Disease

  • Multiple MyelomaAutologous stem cell transplant accounts for most hematopoietic stem cell transplants according to CIBMTR in 2016 in the United States. Studies have shown increased overall survival and progression-free survival in patients younger than 65 years old when consolidation therapy with melphalan is initiated followed by autologous stem cell transplantation and lenalidomide maintenance therapy. The study showed a favorable outcome of high-dose melphalan plus stem-cell transplantation when compared with consolidation therapy with melphalan, prednisone, lenalidomide (MPR). It also showed a better outcome in patients who received maintenance therapy with lenalidomide.
  • Hodgkin and Non-Hodgkin Lymphoma  – Studies have shown that chemotherapy followed by autologous stem cell transplantation in cases of recurrent lymphomas (HL and NHL) that do not respond to initial conventional chemotherapy have better outcomes. A randomized controlled trial by Schmitz N et al. showed a better 3-year outcome of high-dose chemotherapy with autologous stem cell transplant compared to aggressive conventional chemotherapy in relapsed chemosensitive Hodgkin lymphoma. However, the overall survival was not significantly different between the two groups. The number of hematopoietic stem cell transplant recipients comes second after multiple myeloma according to CIBMTR.
  • Acute Myeloid Leukemia Allogenic stem cell transplant has shown to improve outcomes in patients with AML who fail primary induction therapy and do not achieve a complete response and may prolong overall survival. The study recommended that early HLA typing for patients with AML can help if they fail induction therapy and are considered for bone marrow transplant.
  • Acute Lymphocytic Leukemia Allogenic stem cell transplant is indicated in refractory and resistant cases when induction therapy fails for the second time in inducing remission. Some studies suggest an increased benefit of allogeneic hematopoietic stem cell transplant in patients with high risk ALL including patients with Philadelphia chromosome and those with t(4, 11).
  • Myelodysplastic Syndrome Allogenic stem cell transplant is considered being curative in cases of disease progression and is only indicated in intermediate- or high-risk patients with MDS.
  • Chronic Myeloid Leukemia/Chronic Lymphocytic LeukemiaRecipients with these two diseases come at the bottom of the list of patients who received allogeneic stem cell transplant in 2016. Hematopoietic stem cell transplantation has shown high cure rates but with available treatments like tyrosine kinase inhibitors and high success rates with the low adverse risk profile, HSCT is reserved for patients with the refractory disease to first-line agents in CML.
  • Myelofibrosis, Essential Thrombocytosis, and Polycythemia Vera Allogenic stem cell transplant has shown to improve outcomes in patients with myelofibrosis and those who had a diagnosis of myelofibrosis that was preceded by essential thrombocytosis and polycythemia vera.
  • Solid TumorsAutologous stem cell transplant is considered the standard of care in patients with germ cell tumors (testicular tumors) that are refractory to chemotherapy (after the third recurrence with chemotherapy). HSCT has also been studied in medulloblastoma, metastatic breast cancer, and other solid tumors.

Non-Malignant Diseases

  • Aplastic Anemia Systematic and retrospective studies have suggested an improved outcome with hematopoietic stem cell transplant in acquired aplastic anemia when compared with conventional immunosuppressive therapy. Allogenic stem cell transplant has shown better outcomes when it was collected from bone marrow compared to peripheral blood in a study that involved 1886 patients with acquired aplastic anemia. Patients with aplastic anemia need a preparative regimen given they still can develop immune rejection to the graft.
  • Severe Combined Immune Deficiency Syndrome (SCID) – Large retrospective studies have shown increased overall survival in infants with SCID when they received the transplant early at birth before the onset of infections.
  • Thalassemia – Allogenic stems transplant from a matched sibling donor is considered an option to treat Thalassemia and has shown 15-year survival reaching 80%. However, recent retrospective data showed similar overall survival compared with conventional treatment that consists of multiple transfusions in the case of thalassemia.
  • Sickle Cell Anemia – Allogenic stem cell transplant is recommended for the treatment of sickle cell disease.
  • Other Nonmalignant Diseases  – Stem cell transplant has been used in the treatment of chronic granulomatous disease, leukocyte adhesion deficiency, Chediak-Higashi syndrome, Kostman syndrome, Fanconi anemia, Blackfan-Diamond anemia, and enzymatic disorders. Moreover, the role of stem cell transplant is being explored in autoimmune diseases including systemic sclerosis, systemic lupus erythematosus, and has already shown promising results in cases like relapsing-remitting multiple sclerosis.

Bone marrow transplants can benefit people with a variety of both cancerous (malignant) and noncancerous (benign) diseases, including:

  • Acute leukemia
  • Adrenoleukodystrophy
  • Aplastic anemia
  • Bone marrow failure syndromes
  • Chronic leukemia
  • Hemoglobinopathies
  • Hodgkin’s lymphoma
  • Immune deficiencies
  • Inborn errors of metabolism
  • Multiple myeloma
  • Myelodysplastic syndromes
  • Neuroblastoma
  • Non-Hodgkin’s lymphoma
  • Plasma cell disorders
  • POEMS syndrome
  • Primary amyloidosis

In which diseases and at which stages bone marrow transplant is employed?

Acute myeloblastic leukemia

  • In acute myeloblastic leukemias that develop after myelodysplastic syndrome.
  • In patients with acute myeloblastic leukemia without any t(8;21), t(15;17), (Inv 16) abnormality.
  • In patients who do not respond to remission induction therapy.
  • In patients with Flt-3positive acute myeloblastic leukemia.

Acute lymphoblastic leukemia

  • In patients with unfavorable cytogenetic findings such as Philadelphia chromosome, 11q23 positive.
  • In patients with leukocyte counts in excess of 30-50 thousand microliters.
  • In patients with the central nervous system or testicle involvement.
  • In patients who do not respond to initial remission induction therapy.

Myelodysplastic syndrome

  • In patients with blast rate >5%.
  • In patients with Intermediate 1, Intermediate 2 or a higher risk score.
  • In patients with cytopenia in more than one sequence

Non-Hodgkin’s lymphomas

  • 1. In diffuse large cell lymphomas:
  • Upon first relapse (recurrence of the disease after the treatment)
  • Upon the first remission in patients with high, high intermediate risk.
  • 2. Mantle cell lymphoma; after initial treatment
  • 3. Follicular lymphoma;
  • Patients who do not respond sufficiently to initial treatment.
  • Patients with first remission shorter than > 12 months
  • Patients with a 2nd relapse (disease recurring).
  • Patients experiencing conversion into diffuse large B cell lymphoma.
  • Hodgkin’s lymphoma
  • Patients who fail to start remission with initial treatment.
  • Patients who respond to initial treatment, but later experience a relapse.
  • Multiple myeloma
  • Subsequent to initial treatment (after reduction of protein M with 2-4 courses of chemotherapy).

What are bone marrow transplantation suitability criteria?

  • Criteria for Autologous Stem Cell Transplant (Multiple Myeloma, Hodgkin’s and Non-Hodgkin’s Lymphoma etc.):
  • Heart ejection fraction > 50%,
  • Liver function tests should not exceed twice the normal limits,
  • Lung function tests: DLCO > 60 %,
  • Good patient performance.

Criteria for Myeloablative Allogeneic Stem Cell Transplant

  • Age < 55,
  • HLA matching sibling (6 out of 6 or 5 out of 6 markers),
  • Heart ejection fraction > 50%,
  • Normal liver function tests,
  • Lung function tests; DLCO > 60%.

Criteria for Non-Myeloablative (Reduced Dose Regime) Allogeneic Stem Cell Transplant

  • Age < 65,
  • HLA matching sibling or relative.

What are bone marrow diseases?

  • Acute Myeloblastic Leukemia
  • Acute Lymphoblastic Leukemia
  • Non-Hodgkin’s Lymphoma
  • Hodgkin’s Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Chronic Myelocytic Leukemia
  • Chronic Lymphocytic Leukemia
  • Aplastic Anemia
  • Paroxysmal Nocturnal Hemoglobinuria
  • Primary Amyloidosis
  • Solid Cancers: Testicle cancer, ovarian cancer
  • Hereditary Diseases: Hemoglobinopathies

Contraindications of Bone Marrow Transplant

There are no absolute contraindications for hematopoietic stem cell transplant.

Rules for bone marrow transplant

These rules have been prepared as a guide for patients and their relatives.

  • Stick to the physician’s prescription in using all medications.
  • Make sure to come for regular check-ups. Please, arrive on an empty stomach and without having used any medication.
  • Chemotherapy will inhibit the optimum functioning of the immune system for about a year. This is why it is very important to give extra care and attention to personal hygiene, nutrition, use of protective masks, accepting visitors, handshakes, and sexual relations throughout the entire year.
  • Instructions for daily life after bone marrow transplant
  • Your home should be especially clean following the transplant. Allocate a separate room for the patient. Remove dust magnet such as thick carpets and curtains from this room. Do not clean and air the patient’s room which he/she is still inside. If the room/home lacks central heating, make sure to light and clean the fire stove when the patient is outside the room. Adjust the room temperature carefully.
  • The patient’s room must be away from any type of construction activity.
  • All house plants and any kind of pet including cats, dogs, fish, and birds must be removed from the house for a year due to the risk of infection.
  • Make sure to keep the rest of the house equally clean and tidy.
  • Pay attention to land hygiene, take a wash at least two times a day, allocate a separate towel for the patient, and prevent its use by anyone else. Wash and iron the towel after each use. Take showers instead of baths, and use only moisturizing soaps.
  • Use a paper towel for hand and face hygiene.
  • Do not have guests for the first 100 days. Reduce the number of guests as much as possible in the subsequent period. Refrain from close contact including kissing, handshaking, and cuddling.
  • Change the patient’s bed linen at least twice a week, frequently air the mattress.
  • Do not use feather and wool-stuffed pillows.
  • Make sure to wash all new clothes before use. Do not use corduroy or plush textiles.
  • Make sure that the patient uses two masks whilst traveling or outdoors.
  • Patients should not swim for a year (sea or pool) and should not use saunas.
  • Prevent direct contact with sunlight for one year. Walks should be taken in the afternoon.
  • Women should not get epilation for one year. Depilatory creams may be used if the physician approves.
  • Give extra care to hygiene when getting the patient’s haircut.
  • Brush teeth with a soft brush 3 times a day, try not to get gums bleeding.
  • Do not use deodorants, perfumes, makeup, or hair dye for a year.
  • Do not smoke or consume alcohol, steer clear of smoky, dusty, and dirty environments.
  • Do not come in contact with people who have cold, flu, or infection.
  • Immediately seek medical attention in case of bleeding, bruising, and swelling.
  • Dress according to climate, avoid getting ill.
  • Menstruation irregularities may develop in women following the transplant. Seek medical attention from the gynecology department in accordance with the physicians’ recommendations.
  • Treatment will cause a loss in a sense of thirst, hunger, and taste for the first three months after the transplant. This is why patients have to drink three liters of water per day for a year. Drinking less can result in serious electrolyte disorder thus increasing the risk of getting sick. Liquid intake may also be supported by drinking milk, diluted yogurt, tea, fruit juice, or soup. Chew sugar-free chewing gum for building an appetite or suck on sweets for a sense of taste. Drink homemade lemonade 30 minutes before meals, if feeling nauseous.
  • Do not drink spring water from unknown sources. Only drink bottled water.
  • Use only pasteurized milk and cheese.
  • Milk taken outside should be boiled for 15 minutes.
  • Take single-use pasteurized and homemade yogurt.
  • Thoroughly rinse all fruit and vegetables, leave them in water with vinegar for 30 minutes, and peel all skin before consuming.
  • Eat seasonal fruit and vegetables. Avoid consuming processed foods and drinks with additives.
  • Thoroughly cook all food. Strictly avoid eating salami, sausage, bacon, cured meat, spices, raw onions and garlic, tomato paste, animal fat, innards, legumes, pickles, creams, kebabs, pizzas, burgers and any sort of fast foods.
  • Thoroughly cook all meats and eggs, make sure eggs are not cracked.
  • Do not crack nuts with your teeth, use nutcrackers.
  • Refrain from eating strawberries as they grow too close to the soil.
  • Do not eat frozen, stale, or canned food. Food should be consumed in 24 hours.
  • Store food in airtight containers.
  • Use latex gloves to prepare food.
  • Use mask whilst preparing food for the patient.
  • Pay attention to expiration dates for all products and foods.
  • Do not discuss distressing issues with the patient. Keep patient’s spirit high


Special equipment exists for the collection, preservation, and administration of stem cell products. An interprofessional team approach is a mainstay of ensuring the high-quality collection and infusion of stem cell products.

The group of specialists involved in the care of patients going through a transplant is often referred to as the transplant team. All individuals work together to give the best chance for a successful transplant. The team consists of the following:

  • Healthcare providers – Healthcare providers who specialize in oncology, hematology, immunology, and bone marrow transplantation.
  • Bone marrow transplant nurse coordinator – A nurse who organizes all aspects of care provided before and after the transplant. The nurse coordinator will provide patient education, and coordinates the diagnostic testing and follow-up care.
  • Social workers – Professionals who will help your family deal with many issues that may arise, including lodging and transportation, finances, and legal issues.
  • Dietitians – Professionals who will help you meet your nutritional needs before and after the transplant. They will work closely with you and your family.
  • Physical therapists – Professionals will help you become strong and independent with movement and endurance after the transplantation.
  • Pastoral care – Chaplains who provide spiritual care and support.
  • Other team members – Several other team members will evaluate you before transplantation and will give follow-up care as needed. These include, but are not limited to, the following:
    • Pharmacists
    • Respiratory therapists
    • Lab technicians
    • Infectious disease specialists
    • Dermatologists
    • Gastroenterologists
    • Psychologists

An extensive evaluation is completed by the bone marrow transplant team. The decision for you to undergo a bone marrow transplant will be based on many factors, including the following:

  • Your age, overall health, and medical history
  • Extent of the disease
  • Availability of a donor
  • Your tolerance for specific medicines, procedures, or therapies
  • Expectations for the course of the disease
  • Expectations for the course of the transplant
  • Your opinion or preference


Preparation includes:

  • Preparative regimen
  • Collection of hematopoietic stem cells
  • Instant infusion or cryopreservation followed by infusion


Mechanism of Action

The mechanism of action of stem cell transplant against malignancy in leukemia is based on the effect of the graft and donor immunity against malignant cells in recipients. These findings were demonstrated in a study that involved over 2000 patients with different leukemia. These patients received stem cell transplantation and showed that the lowest rate of relapses was in patients who received non-T-cell-depleted bone marrow cells and in those who developed GVHD compared to patients who received T-cell-depleted stem cells, those who did not develop GVHD, and patients who received syngeneic grafts. These findings support the notion that donor cellular immunity plays a central role in the engraftment’s efficacy against tumor cells.

The mechanism of action in autoimmune diseases is believed to be secondary to the increase in T-cell regulatory function which promotes immune tolerance. However, more studies are still needed to determine the exact pathophysiology.

In hemoglobinopathies, the transplanted stem cells produce functional cells after engraftment that replaces the diseased cells.

HLA Typing and Administration

HLA typing is an important step to determine the best donor suitable for stem cell collection. In theory, matched, related donors are the best candidates, followed by matched unrelated donors, cord blood, and then haploidentical donors. HLA typing is analyzed at either an intermediate-resolution level, which entails the detection of a small number of matched alleles between the donor serum and the recipient, or at a high-resolution level to determine the specific number of polymorphic alleles at a higher level. PCR and next-generation sequencing are used for HLA typing, and the results are reported as a score correlating with a match of two alleles for a specific HLA type. Different institutions use a different number of HLA subtypes for eligibility of donors but according to studies that showed matching for HLA-A, B, C, and DRB1 at a high-resolution level were associated with improved survival and outcomes. Recommendations about donor HLA assessment and matching have been proposed by the Blood and Marrow Transplant Clinical Trials Network (BM CTN).

The process may vary depending on the source of the stem cell site collection, whether it is bone marrow, peripheral blood, or cord blood. Moreover, there is a slight difference based on whether it is autologous, allogeneic, or syngeneic. For example, the procedure consists of initial mobilization of stem cells, in which peripheral blood stem cells are collected given the low number and the need for high levels of progeny cells, and then this is followed by a preparative regimen and finally, infusion.

Mobilization and collection involved the use of medication to increase the number of stem cells in the peripheral blood given that there are not enough stem cells in the peripheral blood. The agents used include granulocyte colony-stimulating factors (G-CSF) or chemokine receptor 4 (CXCR4) blockers like plerixafor. G-CSF is believed to enhance neutrophils to release serine proteases which lead to a break of vascular adhesion molecules and the release of hematopoietic stem cells from the bone marrow. Plerixafor blocks the binding of stromal cell-derived factor-1-alpha (SDF-1) to (CXCR4) which leads to the mobilization of stem cells to the peripheral blood. CD34+ is considered the marker for progenitor hematopoietic stem cells in the peripheral blood, and usually, a dose of 2 to 10 x 10/kg CD34+ cells/kg is needed for proper engraftment. Chemotherapy can be used in some instances for mobilization of hematopoietic stem cells; this process is termed chemoembolization.

The usual site of bone marrow collection is the anterior or posterior iliac crest. The procedure can be performed under local or general anesthesia. Complications include pain, fever, and serious iatrogenic complications can occur in less than 1% of cases. Multiple aspirations are done with each aspirate containing 15 mL. The goal is to collect up to 1 to 1.5 L of bone marrow product from the aspirations. The dose of nucleated cells from bone marrow should range between 2 to 4 x 10 cells/kg as studies showed that overall survival and long-term engraftment is strongly influenced by cell dose in allogeneic hematopoietic stem cell transplantation.

The preparative regimen consists of administration of chemotherapy with or without total body irradiation for the eradication of malignant cells and induction of immune tolerance for the transfused cells to engraft properly. This process is not only limited to patients with malignancies but also extends to cases like aplastic anemia and hemoglobinopathies given that these patients have an intact immune system that could cause graft failure if there is no conditioning.

The preparative regimen is divided into myeloablative conditioning and reduced-intensity conditioning. The preparative regimen depends on the disease being treated, existing comorbidities, and the source of the harvested hematopoietic stem cells. The preparative regimen consists of chemotherapy, total body irradiation, or both. There are different combination regimens used in the preparative period, and the choice of the regimen depends on the disease being treated, existing comorbidities, and previous exposure to radiation.

In the special case of SCID, there is no need for a preparative regimen in patients receiving from HLA-matched siblings given that there are no abnormal cells that are needed to be eliminated and because immunosuppression caused by SCID can prevent graft rejection. Reduced-intensity conditioning is preferred in patients with prior radiotherapy, older age, the presence of comorbidities, and history of extensive chemotherapy before BMT. The advantages of using reduced-intensity conditioning include less need for transfusion due to the transient post-transplant pancytopenia and less damage to the liver in cases of chemotherapy and lung due to radiation. However, the relapse rates are higher, but these regimens are more tolerated with a better safety profile in a specific patient population. Most of the chemotherapies used in preparative regimens consist of either potent immunosuppressive agents (high doses of cyclophosphamide 60 mg/kg IV), alkylating agents especially busulfan 130 mg/m2 IV, nucleoside analogs (fludarabine 40 mg/m2) and other agents like melphalan, antithymocyte globulin, rituximab, gemcitabine, and many others. Total body irradiation (TBI) is performed using fractionated doses because it has shown less pulmonary toxicity when compared with one dose regimen. The administration of the preparative regimen should immediately precede the bone marrow transplantation, and as a general rule, the effect of the regimen should produce bone marrow suppression within 1 to 3 weeks of administration.

Reinfusion of either fresh or cryopreserved stem cells can occur in an ambulatory setting and takes up to 2 hours. Before the infusion begins, quality measures are performed to ensure the number of CD34+ cells is sufficient.

Rehabilitation after stem cell transplant

The process of stem cell transplant doesn’t end when you go home. You’ll feel tired, and some people have physical or mental health problems in the rehabilitation period. You might still be taking a lot of medicines. These ongoing needs must now be managed at home, so caregiver and friend/family support is very important.

Transplant patients are followed closely during rehab. You might need daily or weekly exams along with things like blood tests, and maybe other tests, too. During early rehab, you also might need blood and platelet transfusions, antibiotics, or other treatments. At first you’ll need to see your transplant team often, maybe even every day, but you’ll progress to less frequent visits if things are going well. It can take 6 to 12 months, or even longer, for blood counts to get close to normal and your immune system to work well. During this time, your team will still be closely watching you.

Some problems might show up as much as a year or more after the stem cells were infused. They can include:

  • Graft-versus-host disease (in allogeneic transplants)
  • Infections
  • Lung problems, such as pneumonia or inflammation that makes it hard to breathe
  • Kidney, liver, or heart problems
  • Low thyroid function
  • Overwhelming tiredness (fatigue)
  • Limited ability to exercise
  • Slowed growth and development (in children)
  • Cataracts
  • Reproductive or sexual problems, like infertility, early menopause, pain or discomfort during sex, or loss of interest in sex
  • New cancers caused by the transplant

Other problems can also come up, such as:

  • Memory loss, trouble concentrating
  • Emotional distress, depression, body image changes, anxiety
  • Social isolation
  • Changes in relationships
  • Changes in how you view the meaning of life
  • Feeling indebted to others
  • Job and insurance concerns

What complications and side effects may happen following BMT?

Complications may vary, depending on the following:

  • Type of marrow transplant
  • Type of disease requiring a transplant
  • Preparative regimen
  • Age and overall health of the recipient
  • The variance of tissue matching between donor and recipient
  • Presence of severe complications

The following are complications that may happen with a bone marrow transplant. However, each individual may experience symptoms differently. These complications may also happen alone, or in combination:

  • Infections – Infections are likely in the patient with severe bone marrow suppression. Bacterial infections are the most common. Viral and fungal infections can be life-threatening. Any infection can cause an extended hospital stay, prevent or delay engraftment, and/or cause permanent organ damage. Antibiotics, antifungal medicines, and antiviral medicines are often given to try to prevent serious infection in the immunosuppressed patient
  • Low platelets and low red blood cells – Thrombocytopenia (low platelets) and anemia (low red blood cells), as a result of nonfunctioning bone marrow, can be dangerous and even life-threatening. Low platelets can cause dangerous bleeding in the lungs, gastrointestinal (GI) tract, and brain.
  • Pain – Pain-related to mouth sores and gastrointestinal (GI) irritation is common. High doses of chemotherapy and radiation can cause severe mucositis (inflammation of the mouth and GI tract).
  • Fluid overload – Fluid overload is a complication that can lead to pneumonia, liver damage, and high blood pressure. The main reason for fluid overload is because the kidneys cannot keep up with a large amount of fluid being given in the form of intravenous (IV) medicines, nutrition, and blood products. The kidneys may also be damaged from disease, infection, chemotherapy, radiation, or antibiotics.
  • Respiratory distress – Respiratory status is an important function that may be compromised during transplant. Infection, inflammation of the airway, fluid overload, graft-versus-host disease, and bleeding are all potentially life-threatening complications that may happen in the lungs and pulmonary system.
  • Organ damage – The liver and heart are important organs that may be damaged during the transplantation process. Temporary or permanent damage to the liver and heart may be caused by infection, graft-versus-host disease, high doses of chemotherapy and radiation, or fluid overload.
  • Graft failure – Failure of the graft (transplant) taking hold in the marrow is a potential complication. Graft failure may happen as a result of infection, recurrent disease, or if the stem cell count of the donated marrow was insufficient to cause engraftment.
  • Graft-versus-host disease – Graft-versus-host disease (GVHD) can be a serious and life-threatening complication of a bone marrow transplant. GVHD occurs when the donor’s immune system reacts against the recipient’s tissue. As opposed to an organ transplant where the patient’s immune system will attempt to reject only the transplanted organ, in GVHD the new or transplanted immune system can attack the entire patient and all of his or her organs. This is because the new cells do not recognize the tissues and organs of the recipient’s body as the self. Over time and with the help of medicines to suppress the new immune system, it will begin to accept its new body and stop attacking it. The most common sites for GVHD are the GI tract, liver, skin, and lungs.

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Below is a glossary of common terms used when discussing the bone marrow transplant (BMT) process.

Acyclovir: A drug used specifically against and for the prevention of herpes virus; given IV or orally.
Allogeneic Transplant: A transplant between 2 individuals who are not genetically identical.
Alopecia: Hair loss
Amphotericin: A drug used specifically against fungal infections: given IV.
ANC: Absolute Neutrophil Count represents the total number of white cells that are capable of fighting bacterial infections.
Anemia: A condition in which blood has a low number of red blood cells. Signs and symptoms of anemia may include: fatigue, weakness, pale color, headaches, dizziness, low blood pressure and elevated heart rate.
Antibodies: Protein substances in the blood stream that react against bacteria, viruses and other materials harmful to the body.
Antibiotics: Drugs used to fight infections.
Antigen: A chemical (sometimes a protein) recognized by the body’s immune system as being foreign.
Aplastic anemia: A disease where the bone marrow does not produce an adequate number of red cells, white cells and platelets.
ATG: Anti-thymocyte globulin is an antibody made in horses or rabbits against T-cells and used to increase the likelihood of engraftment in bone marrow transplant recipients or to treat graft vs. host disease.
Autologous transplant: A transplant in which the donor and recipient are the same person.
Bactrim/Septra: A medication taken IV/orally to prevent gastrointestinal infections as well as a type of lung infection called pneumocystis.
Betadine: Brown soap that effectively kills germs when applied to the skin.
Biopsy: The removal of a small piece of tissue from the body for purposes of diagnosis (i.e., bone marrow, skin, liver, lung).
Blood type: Blood cells contain factors that are not the same in all people. Before a transfusion can occur, blood samples from the donor and recipient are classified as type A, B, AB, or 0. Another test called “cross match” ensures the compatibility of the blood between donor and recipient.
BMTU: Bone Marrow Transplant Unit
Bone marrow: A spongy material found in the center of the bones that contains stem cells that manufacture blood cells. The 3 major types of blood cells that bone marrow stem cells produce are red blood cells (RBC), white blood cells (WBC) and platelets. Each has an important function. See red blood cell, white blood cell and platelets.
Bone Marrow Transplant (BMT): A procedure in which bone marrow stem cells are collected from one individual (the donor) and given to another (the recipient). The stem cells can be collected either directly from the bone marrow or from the blood by a procedure called leukapheresis. Sometimes the patient serves as his or her own bone marrow stem cell donor.
Busulfan: A chemotherapy drug that is given prior to bone marrow transplantation.
Cancer: Diseases that are characterized by the uncontrolled and abnormal growth of cells. Examples: leukemia, lymphoma, and neuroblastoma.
CBC: The Complete Blood Count includes the level of hemoglobin and number of red and white blood cells and platelets in the blood.
CD34: A unique marker that is found on the surface of bone marrow stem cells. Special chemicals called monoclonal antibodies can be used to identify the CD34 positive stem cells in the bone marrow or blood. CD34 positive stem cells can be purified and T cell depleted for transplantation from donors who are mismatched (haplocompatible) with the recipient.
Central line or catheter: A central line or central venous catheter is a soft flexible tube that is placed under the skin and then directed into a large vessel leading into the heart. The catheter allows fluids, medications, nutrition and blood products to be given without sticking the patient with a needle. Blood can also be drawn through the catheter for laboratory tests. The catheter may have either one or two tubes or lumen.
Chemotherapy: Drugs primarily used to destroy cancer cells but also used in bone marrow transplant patients without cancer in order to ensure successful engraftment. These drugs have side effects that affect other normal cells in the body. Another name commonly used is “chemo.”
Chimerism: The state in which donor cells have durably engrafted in the recipient. Full donor chimerism implies that 100% of bone marrow and blood cells are of donor origin, while mixed or partial chimerism means that recipient cells are also present.
Clotrimazole: Anti-fungal agent. See Mycostatin.
Conditioning regimen: Term used for those chemotherapy drugs and sometimes radiation that collectively prepare the body for transplant. The conditioning regimen usually takes 6-8 days to complete.
Culture: A laboratory procedure in which samples of blood, urine or other body fluid are used to determine the presence of an infection.
Donor: The family member (parent, brother or sister) or unrelated volunteer who donates his/her bone marrow stem cells. Sometimes the patient serves as his or her own donor. On the day of transplant, the donor either goes to the operating room and under general anesthesia has multiple bone marrow aspirations (bone marrow harvest) to remove a portion of bone marrow, or undergoes a procedure called leukapheresis to collect bone marrow stem cells from the blood.
EKG: Electrocardiogram – a machine that records electrical measurements of the heart’s impulses.
Engraftment: The successful growth of donor bone marrow stem cells in the recipient.
Erythrocytes: Red blood cells.
Fludarabine: An immunosuppressive chemotherapy drug that is given prior to transplant in order to prevent rejection of the donor cells by the recipient’s immune system.
Gastrointestinal (GI): Pertains to the digestive tract which includes the mouth, throat, esophagus, stomach, small and large intestine and rectum.
G-CSF Granulocyte Colony Stimulating Factor. A drug that is found naturally in the body and that stimulates the production of granulocytes (neutrophils) by the bone marrow. GCSF is also used to increase the number of stem cells circulating in the blood.
Graft vs. Host Disease
A reaction between the transplanted T lymphocytes of the donor (graft) and the tissues/organs of the patient (host). The T- cells of the donor graft can attack the recipient’s tissues. The skin, GI tract, liver and other organs can be affected.
Granulocyte: A type of white blood cell that helps fight infections.
Haplocompatible: When the donor and recipient share half of their HLA antigens. All parents are haplocompatible with their children since children inherit half of their HLA antigens from their mother and half from their father.
Hematocrit: A measure of red blood cell volume. A normal hematocrit (Hct) is between 36-48. A low Hct (for example <20) may result in the need for a red blood cell transfusion.
Hematology: The branch of medicine that studies and treats diseases of the blood and blood forming organs. A hematologist is a physician that specializes in this area of practice.
Hematopoietic Referring to the tissue that produces the components in the blood including red cells, white cells and platelets, that is, bone marrow. Another term for a bone marrow transplant (BMT) is “hematopoietic stem cell transplant (HSCT)”
Hemoglobin: A measure of red blood cell volume.
Hemoglobinopathy: A disorder of the bone marrow cells that produce erythrocytes (red blood cells). Two hemoglobinopathies for which a bone marrow transplant is commonly done are thalassemia major and sickle cell disease.
Hemorrhage: Refers to a large amount of blood loss over a short period of time.
HEPA filter: A High Efficiency Particulate Aerosol filter found in each of the transplant rooms which prevents harmful germs from entering the room via the air system.
Histocompatibility: The degree of tissue similarity between the donor and recipient that will determine how easily the donor cells will be accepted and/or the likelihood and severity of GVHD.
Histocompatibility (HLA) typing: Blood tests of the tissue typing system. The HLA and MLC determine the likeness between potential donor – recipient pairs.
HLA: Human Leukocyte Antigen. See histocompatibility typing.
Hyperalimentation: Intravenous administration of nutrients needed by the body. It is also called total parenteral nutrition (TPN). The nutrients in the form of fluid are given through the central line.
Immune system: The body’s system of defenses against disease. The immune system is primarily composed of white blood cells and antibodies.
Immunology: A branch of medicine which studies the body’s natural defense mechanisms against disease. An immunologist is a physician that specializes in this area of practice.
Immunosuppressed: The state where the body has a reduced ability to adequately fight infections.
Infection: Invasion of any part of the body by germs. Bacteria, viruses, and fungi are the major germs that infect transplant recipients.
Informed consent: The process whereby a patient/parent/legal guardian is given information about a specific surgery or treatment (i.e., bone marrow transplant). All potential risks and benefits must be understood prior to the signing of a consent form. It is a legal document that gives the physician permission to perform the procedure.
Intralipid: Usually given in conjunction with hyperalimentation. This IV solution contains fat and provides the body with needed nutrients.
Intravenous (IV): The administration of fluids/medications directly into a vein.
Isolation: Procedures (for example, handwashing) in the transplant rooms that minimize the exposure of transplant patients to infection.
IV pump: The machine that delivers fluids and medications intravenously.
Jugular: Refers to the veins in the neck in which catheters may be placed for leukapheresis procedures.
Kostmann’s syndrome: An inherited disorder of neutrophils in which affected children present with severe infections and very low to absent neutrophil counts; also called severe congenital neutropenia.
Leukapheresis A procedure that is used to collect bone marrow stem cells from the blood (see PBSC). Typically, the donor of the PBSC is treated prior to the procedure with several days of GCSF injections to mobilize the bone marrow stem cells into the circulating blood. The blood is then passed through a machine that collects that part of the blood containing the stem cells. The remaining blood is returned to the donor.
Leukemia: A cancer of the bone marrow that is characterized by the abnormal growth of white blood cells.
Leukocyte: A type of white blood cell.
LFT’s: Liver function tests are measurements from blood samples that reveal how well the liver is working.
Lymphocytes: A type of white blood cell that is especially important in fighting viral and bacterial infections as well as in rejecting transplants.
Lymphoma: Cancer of the lymph nodes.
Metastatic: Refers to cancers in which there has been spreading to distant parts of the body from the original or primary site of the tumor.
MLC: Mixed Lymphocyte Culture. Sometimes used in histocompatibility typing in which donor and recipient cells are mixed together in a test tube to determine their compatibility with each other.
Myeloablation: The process of conditioning or preparing a patient for a bone marrow transplant in which the bone marrow stem cells are destroyed or ablated. Generally, the conditioning regimen contains very high doses of chemotherapy and often total body irradiation.
Neuroblastoma: A type of cancer that involves the adrenal gland or nervous system.
Neutrophil: A type of white blood cell that plays a major role in fighting bacterial and fungal infections.
Non-myeloablative: The conditioning regimen prior to transplant in which limited amounts of chemotherapy are administered in order to prevent rejection of the donor bone marrow stem cells without destroying the recipient’s bone marrow.
Nystatin: A medication specifically used to fight a fungal or yeast infection.
Oncology: The study and treatment of cancer. An oncologist is a physician who specializes in this area of practice.
PBSC (peripheral blood stem cells): Peripheral Blood Stem Cells. These are bone marrow stem cells that are circulating in the blood and can be collected by leukapheresis. To increase the number of PBSC donors receive GCSF for several days prior to the leukapheresis.
Pharmacokinetics: The measurement of how a drug is taken up and eliminated by the body. The pharmacokinetics of busulfan is measured in a child who is going to receive this drug as part of his or her conditioning regimen in order to determine the optimal dose for that child.
Phenytoin (Dilantin): A drug used to help prevent seizures. Patients are put on this while they are receiving Busulfan, a chemotherapy that can cause seizures.
PICU: Pediatric Intensive Care Unit.
Platelets: A type of blood cell that is necessary to stop bleeding and allow injured areas to form clots. A normal platelet count is 140,000-300,000. A platelet transfusion may be needed with platelet counts <15,000 or to help stop bleeding.
Quinton catheter: A type of temporary central venous catheter that is inserted into a large vein in the neck and used for leukapheresis. A similar type of central venous catheter for leukapheresis is a Vascath. Both catheters are usually removed after the leukaphersis is complete.
Rad: A unit of measurement in the administration of radiation.
Radiation Therapist: A physician who specializes in the use of radiation in the treatment of diseases.
Radiation Therapy: Treatment using high energy radiation. (See total body irradiation).
Red Blood Cells (RBC): Cells found in the blood responsible for carrying oxygen to tissues in the body.
Severe Combined Immunodeficiency Disease (SCID): A group of inherited diseases characterized by severely abnormal lymphocytes and the inability to make antibodies. Children with SCID are susceptible to infections from bacteria, viruses, and fungi which are ultimately fatal without a bone marrow stem cell transplant.
Stem cells: The youngest bone marrow cell from which other bone marrow cells are formed.
Syngeneic Transplant: A transplant between identical twins.
Total Body Irradiation (TBI): Treatment using radiation to kill cancer cells and/or prepare the body for transplant by destroying diseased cells and suppressing the recipient’s immune system’s ability to reject the donor cells.
Transfusion: A procedure that supplies the body with a specific types of blood cells (red blood cells or platelets) that are low in number.
Umbilical cord blood: The blood that is collected from the placenta after the umbilical cord is separated from a newborn baby. This blood contains large numbers of bone marrow stem cells and can be used as a source of donor cells from a sibling or unrelated donor for a bone marrow transplant.
Vascath: A temporary central venous catheter that is used for leukapheresis procedures. It is usually inserted into a large vein in the neck or the groin and removed once the procedure is over.
Veno-occlusive disease (VOD): A severe complication following a bone marrow transplant in which there is progressive liver failure. VOD may be mild and resolve without any treatment or may be severe and often fatal.
Venous: Referring to veins in the body that carry blood from all of the organs and tissues back to the heart. Central lines and leukapheresis catheters are venous catheters, i.e., they are placed in large veins.
White blood cells (WBC): Cells found in the blood and tissues that aid in fighting infections and making antibodies for the immune system’s attack against disease. There are several types of white blood cells including neutrophils and lymphocytes. The normal WBC is 5,000-10,000
Xenogeneic transplant: A transplant between two different species, for example, bone marrow from a baboon transplanted into a human.
Yeast: A germ that can infect recipients of bone marrow transplants. One kind of yeast or fungus is Candida. Fluconozole is an antibiotic that is given during the transplant period to reduce the risk of fungal infections. Yeast or fungal infections are very dangerous and when yeast is cultured or a yeast infection is suspected a very powerful antibiotic, amphoteracin is usually administered.
Zoster: A viral infection that may occur post bone marrow transplant in a patient who has previously had chicken pox. Zoster or shingles is the reactivation of the chicken pox virus (varicella).



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