INTRODUCTION

As treatment and possible cure for certain malignant disorders, high-doses of chemotherapy and/or radiotherapy are administered in order to destroy the malignant cells. The dose may exceed the tolerance limit of bone marrow and eliminates or nearly eliminates (ablates) the patient’s marrow. Transfer of organ, tissue or cells is known as transplantation and hematopoietic stem cells(HSC) transplantation is a curative therapy for many hematologic (malignant and nonmalignant) and nonhematologic disorders. Features of stem cell is mentioned in Box 61.1.

DEFINITION

Hematopoietic stem cell transplantation is the process of collection and infusion of hematopoietic stem cells obtained from bone marrow [bone marrow transplantation (BMT)] or peripheral blood (blood stem cell transplantation). The source may be either from other individual or own hematopoietic stem cells.

SOURCES OF HEMATOPOIETIC STEM CELLS

•• Bone marrow: This is the richest source of hematopoietic stem cells.

•• Peripheral blood: Few hematopoietic stem cells are present in the circulation, but can be mobilized from bone marrow by administering G-CSF or GM-CSF.

•• Umbilical cord blood: It is easily available following delivery and is a rich source of hematopoietic stem cells.

TYPES OF HEMATOPOIETIC STEMCELL TRANSPLANT

•• Autologous (“from self”): The patient’s own HSCs are removed, cryopreserved and reinfused.

•• Allogeneic (“from different genes”): HSCs are obtained from another individual.

•• Syngeneic (“from same genes”): HSCs are obtained from an identical twin.

INDICATIONS FOR HEMATOPORETIC STEM CELL TRANSPLANTATION

Refer Box 61.2.

AUTOLOGOUS STEM CELL TRANSPLANT

Marrow or peripheral stem cells are obtained from the patient before the high-dose therapy, frozen (cryopreserved) and then reinfused after the high-dose therapy to re-constitute marrow function. 

Different Steps of Autologous Stem Cell Transplantation (Fig. 61.1).

•• Harvesting: During harvesting, bone marrow and/or peripheral HSCs (identified as CD34+ by immunophenotyping) are collected.

•• Processing of HSCs: The collected bone marrow or peripheral blood stem cells are suspended in dimethyl sulfoxide (prevents ice crystallization in the cells) and frozen in liquid nitrogen. The HSCs can survive in frozen state for at least 5 years.

•• Conditioning: Before the autologous transplant, the patient is given a high-dose chemotherapy and/or radiation therapy, sometimes total-body irradiation (TBI). This procedure is called conditioning, the purpose of which is to eradicate the recipient’s hematopoietic and immune system and also malignant tumor cells if any. Conditioning also makes physical space available for HSCs to engraft. In contrast to allogeneic transplantation, autologous transplantation does not require immunosuppression to prevent graft-versus host disease (GVHD).

•• Stem cell transplant: The collected frozen bone marrow or peripheral HSCs are thawed and infused intravenously like a blood transfusion. These stem cells home from the peripheral circulation to the conditioned empty marrow space. Because of conditioning, the patient is pan cytopenic and requires critical care. The high-dose chemotherapy also causes breakdown of the normal mucosal barriers in the mouth and gut resulting in increased susceptibility to infections and painful ulcerations.

•• Post-transplant engraftment: During this stage, the hematopoietic cells produce all the three formed elements of the blood.

ALLOGENEIC STEM CELL TRANSPLANTATION

The HSCs are obtained from an HLA-matched or HLA-mismatched family member (usually a sibling) or an unrelated donor.

 Different Steps of Allogeneic Stem Cell Transplantation (Fig. 61.2)

•• Harvesting: During harvesting, collected bone marrow and/or peripheral HSCs are mixed with mature WBCs, important being lymphocytes. Mature T lymphocytes are the principal effectors of cell-mediated immunity and both therapeutic benefit and toxicities of allogeneic HSC transplant are due to immunologic reactions between donor T cells and recipient cells.

•• Conditioning: This step is similar to autologous HSC transplant. Immunosuppression is to allow engraftment of the transplanted HSCs. The patient’s endogenous lymphocytes must be suppressed by immunosuppression so as to prevent graft-versus-host disease (GVHD).

•• Stem cell transplant: The harvested HSCs are infused into the vein just like a blood transfusion. The stem cells travel and reside in the marrow. Patient requires utmost care during this period similar to autologous transplant.

•• Engraftment: Donor T lymphocytes help donor HSCs engraft. These T lymphocytes are mainly CD8+ and they destroy any remaining host immune cells which may reject the donor HSCs. Depletion of donor T lymphocytes before allogeneic HSC transplant significantly increases the risk of graft failure. But the greatest disadvantage due to the donor T lymphocytes is development of GVHD.

COMPLICATIONS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION

Autologous HSC transplants have fewer immunologic complications but have higher rates of relapse of the disease after transplant. Allogeneic HSC transplants have lower rates of relapse but have more immunologic complications, including GVHD, which can be fatal.

•• Infections: Patients are susceptible to a variety of infections (bacterial, viral and fungal) due to lack of granulocytes, as well as lack of a functioning immune system.

•• Organ toxicity: The other complications include damage to GI tract, liver and lungs.

•• Graft-versus-host disease: GVHD is the major complication that follows allogeneic HSC transplant. This is caused by infused donor T lymphocytes reacting against the recipient’s tissues/organs. Three conditions are necessary for the development of GVHD:

–– An immunocompetent graft (i.e. one containing T cells).

–– HLA mismatch (minor or major) between donor and recipient.

–– An immunosuppressed recipient who cannot mount an immune response to the graft.

If GVHD occurs before 100 days, it is termed as acute GVHD. It often affects three primary target organs simultaneously, namely skin, gastrointestinal (GI) tract and liver. GVHD that occurs after day 100 is termed chronic GVHD and can affect the skin, GI tract, liver, eyes, lungs and joints. GVHD is difficult to treat and in severe cases it is usually fatal.

•• Interstitial pneumonitis, diffuse alveolar hemorrhage

•• Veno-occlusive disease of the liver

•• Hemorrhagic cystitis

•• Cardiac dysfunction.


Points to note:

•• HSC transplantation is used for the treatment of many nonmalignant and malignant disorders.

•• The source of HSCs may be bone marrow, peripheral blood or umbilical cord blood.

•• The types of transplantation include, autologous (“from self”), allogeneic (“from different genes”) or syngeneic (from identical twin).

•• A major complication of mainly allogeneic transplant is GVHD.