Bone marrow transplantation is the most effective method of treating leukemia. A he althy bone marrow administered to a patient restores hematopoietic tissue in the patient's body. But what is needed is a bone marrow donor - a man willing to voluntarily undergo a non-complicated medical procedure. What are the indications for a bone marrow transplant? How is the procedure going? What complications may occur?

Bone marrow transplantationis a procedure performed in a hospital setting, involving the transplantation of hematopoietic stem cells. Their task is to rebuild the patient's hematopoietic system, damaged in the course of a non-neoplastic or neoplastic disease.

Hematopoietic stem cells can be obtained not only from bone marrow, but also isolated from peripheral blood or umbilical cord blood.

Due to the origin of the collected cells, there are 3 types of transplantation:

  • autogenic transplant(the donor of the stem cells is the patient himself)
  • syngeneic transplant(i.e. isogenic, when the donor of the stem cells is the patient's identical twin brother)
  • allograft(the donor of stem cells is an unrelated or related person, but not the recipient's identical twin)

Bone marrow transplant: types

Division of bone marrow transplants according to the origin of the transplanted material:

AUTOGENIC (auto-HSCT, auto- hematopoietic stem cell transplantation)

This is a procedure involving transplantation of the patient's own hematopoietic stem cells, taken from him before the use of myelosuppressive treatment, that is, destroying the bone marrow.

Advantages of Autograft:

  • offers the possibility of using myeloablative treatment with the use of very high doses of chemotherapy or radiotherapy; the effect of such therapy is complete, irreversible destruction of the bone marrow in which the neoplastic process takes place; this model of therapy is advantageous in patients struggling with conditions prone to high dosescytostatics
  • low risk of serious complications after transplantation; graft versus host disease (GVHD) is not common, as the patient is transplanted with his own blood-producing stem cells obtained previously
  • no risk of transplant rejection because the patient's own tissues are transplanted
  • no need for immunosuppressive treatment after transplantation
  • the upper age limit of recipients is 70 years of age, while the final qualification for the procedure takes into account not only the patient's age, but also his general condition, the presence of comorbidities and the advancement of the neoplastic disease

Disadvantages of Autograft:

  • a method of treatment used in patients with low-mass and low-stage neoplastic tumors - otherwise there is a risk of insufficient cleansing of the transplanted material from neoplastic cells and unintentional re-implantation, which may result in recurrence of the disease
  • no positive graft versus leukemia (GvL) response
  • there is a high risk of relapse (approximately 45%)

ISOGENIC (SYNGENIC) TRANSPLACING

This procedure is based on the transplantation of hematopoietic stem cells from his twin brother to the patient. It is very important that siblings are genetically identical, i.e. they must come from a twin pregnancy (homozygous).

ALLOGENIC TRANSPLACEMENT (allo-HSCT)

This is a procedure in which the transplant comes from a person who is not the patient's identical twin. The stem cell donor must be compatible with the recipient for HLA antigens, may or may not be related to them.

Currently, the vast majority of transplants are performed using material collected from unrelated donors.

Advantages of allogeneic transplantation:

  • enables the use of prior chemo- or radiotherapeutic treatment in doses that will cause complete destruction of the diseased bone marrow, similar to autograft
  • bone marrow from a he althy donor is transplanted, so there is no risk of contamination of the graft material with neoplastic cells and recurrence of the disease
  • there may be a favorable graft versus leukemia (GvL) response
  • there is a slight risk of relapse (approx. 10%)

Disadvantages of Allograft:

  • performed on people up to around 60 years of age
  • Due to transplantation of foreign tissues and cells obtained from a donor, the recipient's organism may develop life-threatening complications; as many as 10-30% of patients undergoing the procedure show adverse reactions, which include, first of all, graft versus host disease (GvHD) or opportunistic infections
  • finding a matching donor may be difficult
  • due to transplantation of foreign tissues there is a risk of rejection
  • the need for immunosuppressive treatment after transplantation

Bone marrow transplantation: donor selection

Donor selection for allogeneic bone marrow transplantation concerns the major histocompatibility complex (MHC), which includes many genes encoding human leukocyte antigens (HLA).

Correct donor selection is crucial for the success of the procedure. Otherwise, there is a high probability of many life-threatening complications, such as graft versus host disease (donor cells recognize the recipient's tissues as foreign and destroy them), or rejection of the transplant.

It is worth noting that:

  • no blood group compatibility is required between the donor and recipient
  • there is no age limit above which you cannot donate hematopoietic stem cells
  • the transplant recipient and donor do not have to be of the same sex, there are no contraindications for transplanting a woman's bone marrow to a man and vice versa

Usually the bone marrow donor is a related person, most often the patient's siblings, because there is the highest chance of full HLA compliance with the recipient.

In a situation where no antigenically compatible family donor has been found for the recipient, it is necessary to start searching for an unrelated donor. This is possible thanks to the global register of volunteers who have declared their readiness to donate hematopoietic cells.

Bone marrow transplant: preparing the donor for the procedure

Before collecting the bone marrow from a donor, the doctor must be sure that the bone marrow is he althy and that no infection or neoplastic process develops in his body. The requirement is to execute:

  • detailed blood laboratory tests
  • electrocardiographic examination (EKG)
  • chest X-ray
  • ultrasound of the abdominal cavity

Moreover, infection with human immunodeficiency virus (HIV), hepatitis virus, cytomegalovirus must be ruled out in the donor.(CMV) and Epstein-Barr virus (EBV).

Bone marrow transplant: preparing the patient for the procedure

Each type of hematopoietic stem cell transplantation requires the use of drugs that reduce the recipient's immunity, so it is important to exclude all possible sources of infection and good general condition of the patient before starting the procedure.

Qualification for transplantation should include, inter alia:

  • precise tumor stage assessment
  • performing detailed laboratory tests to assess the functions of the liver and kidneys
  • heart and lung function tests
  • to rule out HIV, CMV, EBV and hepatitis infections

Do not forget to visit the dentist, gynecologist and ENT specialist for a follow-up visit.

Bone marrow transplantation: harvesting cells for transplant

Hematopoietic stem cells can be collected from bone marrow, peripheral blood or umbilical cord blood.

Cells from the donor's bone marrow are collected in the operating theater under general anesthesia.

The procedure consists in repeated needle puncturing of the donor's pelvic bones (exactly the posterior, upper iliac spine).

Take about 15-20 ml / kg of the body weight of the recipient of the bone marrow, i.e. about 1-1.5 liters.

Only this amount of material will contain the right amount of stem cells for the reconstruction of the recipient's marrow (more than or equal to 2x106 / kg of the recipient's body weight).

Bone marrow transplantation: indications for transplant

Indications for hematopoietic stem cell transplantation in accordance with the recommendations of the European Group of Blood and Marrow Transplantation.

Tumors of the hematopoietic and lymphatic systems

  • acute myeloid leukemia
  • acute lymphoblastic leukemia
  • myelodysplastic syndromes
  • chronic myeloid leukemia
  • spontaneous marrow fibrosis
  • diffuse large B-cell lymphoma
  • Burkitt's lymphoma
  • mantle cell lymphoma
  • follicular lymphoma
  • chronic lymphocytic leukemia
  • T cell lymphomas
  • Hodgkin's lymphoma
  • multiple myeloma

Solid tumors:

  • germ cell neoplasms
  • clear cell kidney cancer
  • neuroblastoma
  • ovarian cancer

Non-cancerous diseases:

  • aplastic anemia
  • nocturnal paroxysmal hemoglobinuria
  • Fanconi anemia
  • Blackfan and Diamond anemia
  • thalasemia major
  • sickle cell anemia
  • congenital metabolic disorders
  • autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease)
  • multiple sclerosis
  • amyloidosis (amyloidosis)

The most common indications for auto- and allotransplantation

Indications for AUTO-HSCT

  • acute myeloid leukemia
  • acute lymphoblastic leukemia
  • myelodysplastic syndromes

Indications for ALLO-HSCT

  • plasma myeloma
  • nonhodgkin lymphos
  • Hodgkin's lymphoma

Bone marrow transplantation: course

1st stage - conditioning

The bone marrow transplantation procedure begins with the introduction of intensive anti-cancer therapy, which is called conditioning. It aims to destroy not only the cancer cells, but also the bone marrow recipient's lymphocytes, which could lead to rejection of the transplant.

Conditioning consists in administering to the recipient such high doses of chemotherapeutic agents or combined chemotherapy with radiotherapy to induce irreversible bone marrow destruction. It is a myeloablative treatment.

The main complications of this therapy include:

  • reduced immunity and susceptibility to any infections
  • nausea
  • vomiting
  • gastrointestinal mucosa inflammation
  • appearance of blood strokes
  • hair loss

It is important to inform patients about the possibility of depositing sperm in a sperm bank and freezing the eggs, as such intensive treatment can result in loss or significant reduction of fertility.

II stage - implantation

The stem cells collected from the donor are transplanted into the recipient in the form of a central intravenous infusion, i.e. using a puncture into one of the central veins established in the operating theater.

III stage - early post-transfiguration period

A typical feature of the early post-transfusion period is the occurrence of pancytopenia, i.e. a reduction in the number of all morphotic elements in the blood - erythrocytes, platelets and leukocytes.

IV stage - bone marrow regeneration

Bone marrow transplant: complications

Graft versus host disease (GvHD)

  • acute GvHD (aGvHD)

Acute Graft Versus Host Diseaseoccurs within 100 days after transplantation. It results from an attack by donor T lymphocytes, i.e. cells of the immune system, against the recipient's tissues.

Acute GvHD may resolve or become chronic. It is worth mentioning that this is the leading cause of post-transplant mortality!

Despite the selection of HLA-compatible donors, GvHD and early graft rejection may occur as there are many other antigenic determinants encoded on other chromosomes that are not routinely tested.

aGVHD is a relatively frequent reaction, observed in about 40-70% of patients, therefore it is so important to frequently monitor the condition of patients undergoing the procedure.

Three characteristic symptoms typical of an early GvHD reaction have been described:

  • skin changes such as redness, blisters, generalized erythroderma
  • liver function abnormalities, initially only seen as laboratory abnormalities (increased alkaline phosphatase and bilirubin levels)
  • watery diarrhea

Prevention of the acute graft versus host reaction mainly relies on the correct selection of the tissue donor in the HLA system.

  • chronic (cGvHD, chronic GvHD)

Chronic Graft versus Host Disease occurs more than 100 days after hematopoietic stem cell transplantation. It occurs in approximately 33% of allograft recipients from related donors, but does not occur in autologous transplant recipients.

Donor T cells are responsible for developing this response in recipients, as they recognize the recipient's tissues as foreign and destroy them.

Chronic GvHD disease affects many organs, the symptoms include skin and mucous membranes changes, diseases of the eyes, liver, lungs, as well as pathologies within the gastrointestinal tract.

It is worth mentioning that the mortality in the course of chronic GvHD is much lower than in the course of acute GvHD. There is a limited and generalized form of chronic graft versus host disease.

  • Chronic disease classification transplant versus recipient

Limited Chronic GvHD
(one or both criteria)

Limited skin involvement
Liver dysfunction due to cGvHD
Generalized chronic GvHD

Generalized skin involvement
or
Limited skin involvement and / or liver dysfunction due to cGvHD
and
Liver histopathologyindicates chronic aggressive hepatitis, necrosis or cirrhosis of the liver
or
Eye involvement (Schirmer test <5mm)<5mm)
or
Involvement of the smaller salivary glands or mucosa in a biopsy lips
or
Seizure of any target organ

Graft versus leukemia (GvL)

The graft versus leukemia reaction is observed in allograft recipients, i.e. when hematopoietic stem cells come from related or unrelated donors.

It occurs due to the introduction into the recipient's body of cells of the donor's immune system, T lymphocytes and NK cells, which recognize and destroy the remaining cancer cells in the recipient's body.

Mucositis

Inflammation of the gastrointestinal mucosa is the most common complication observed in patients undergoing bone marrow transplantation, caused by intensive chemotherapy prior to surgery.

The main symptoms are multiple mouth ulcers, nausea, painful abdominal cramps, and diarrhea. Due to severe pain when swallowing, it is essential to start parenteral nutrition.

Severe pancytopenia

Patients undergoing bone marrow transplantation often report a reduced number of all peripheral blood counts, ie red blood cells, leukocytes and platelets. This may result in the occurrence of:

  • severe, life-threatening anemia requiring a transfusion of RBC (concentrated red blood cells)
  • blood coagulation disorders, manifested depending on the degree of thrombocytopenia: ecchymosis, haemorrhage, bleeding from the nose or ears
  • severe bacterial, fungal or viral infections, requiring the administration of antibiotic therapy, antifungal drugs or antiviral drugs, respectively

Infections

Due to decreased immunity, people after bone marrow stem cell transplantation are more susceptible to bacterial and viral infections, as well as fungal infections. The most frequently detected pathogens in recipients include:

  • bacteria: pneumococcus,Hemophilus influenzae
  • viruses: cytomegalovirus, viruses from the groupHerpes
  • fungi:Candida ,Aspergillus ,Pneumocystis carinii

Rejection of transplanted bone marrow

Bone marrow transplant rejection is a serious complication seen in transplant recipientsallogeneic, does not occur in autologous transplant recipients (own bone marrow taken before intensive treatment).

This is a situation in which the transplanted hematopoietic stem cells do not start to proliferate and differentiate, i.e. the process of hematopoiesis does not begin.

Prognosis of transplant patients

Relapses of the disease have been reported in the literature much more frequently in autograft recipients than in allograft recipients. This is probably due to the fact that in the case of own bone marrow transplantation, no graft-versus leukemia reactions were observed, the education of which is very favorable.

Category:

Cardiology