Disease	Allogeneic (%)	Autologous (%)
Severe combined immunodeficiency	90	N/A
Aplastic anemia	90	N/A
Thalassemia	90	N/A
Acute myeloid leukemia
First remission	55-60	50
Second remission	40	30
Acute lymphocytic leukemia
First remission	50	40
Second remission	40	30
Chronic myeloid leukemia
Chronic phase	70	ID
Blast crisis	15	ID
Chronic lymphocytic leukemia	50	ID
Myelodysplasia	45	ID
Multiple myeloma	30	35
Non-Hodgkin’s lymphoma, first relapse, second remission	40	40
Hodgkin’s disease, first relapse, second remission	40	50

ID, Insufficient data; N/A, not applicable.

^∗These estimates are based on data reported by the International Bone Marrow Transplant Registry.

What Are Progenitor Blood Cells?

Progenitor cells have the ability to evolve into different types of cells. Bone marrow and peripheral blood progenitor cells are capable of reconstituting a person’s immune system because they contain the precursor to the cells that make up the blood: lymphocytes, granulocytes, macrophages, and platelets. Progenitor cells that circulate in the bloodstream are called peripheral blood stem cells (PBSCs). PBSCs are found in much smaller quantities in the circulating blood than in the bone marrow. Hematopoietic stem cells are found in very small numbers in the peripheral blood and greater numbers in the marrow.

The hematopoietic stem cell population is not fully characterized, but the cell marker, CD34+ antigen, identifies a population of stem cells that can repopulate the bone marrow after chemotherapy. The required minimal dose of CD34+ cells is difficult to define, but most transplantation centers will infuse a minimal dose of 2 × 10⁶ CD34+ cells/kg patient weight in the autologous and allogeneic PBSC setting.

Historically, the dose of bone marrow has been based on the nucleated cell (NC) count (i.e., 2 to 4 × 10⁸ NC/kg recipient weight). There is no established amount of CD34+ bone marrow stem cells to infuse because there may be more primitive cells, and therefore likely to be CD34− cells, in the marrow that are capable of reconstituting the recipient’s marrow.

Types of Transplants

There are three major types of transplants:

• Allogeneic

• Syngeneic

• Autologous

In an allogeneic setting, a person receives bone marrow or PBSCs from a related or an unrelated donor, depending on the availability of a good human leukocyte antigen (HLA) match. Because HLA tissue types are inherited, patients are more likely to find a matched donor from within their own family, racial, or ethnic group. In syngeneic transplantation, patients receive stem cells from their identical twin. Patients who undergo an autologous transplantation have donated their own cells after PBSC mobilization with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).

Traditional Treatment Options

To understand why bone marrow and PBSCs are used and how they work, it is helpful to understand how chemotherapy and radiation therapies affect these cells. Chemotherapy and radiation target rapidly dividing cells. These therapies are used to treat cancers because cancer cells divide more rapidly than healthy cells. Bone marrow cells also divide at a rapid rate and can be severely damaged or destroyed by high-dose treatment. Without healthy bone marrow, the patient cannot make the blood cells that are able to fight off infections, carry oxygen, and prevent bleeding.

Treatment for cancer includes chemotherapy, radiation therapy, surgery, hormone therapy, and/or immunotherapy. These therapies may be administered alone or in combination to eliminate malignant cells most effectively.

Chemotherapy

Chemotherapy may involve one drug or a combination of two or more drugs, depending on the type of cancer and its rate of progression.

Chemotherapeutic drugs can be divided into the following:

1. Agents that are active against both dividing and nondividing cells

2. Drugs that are active against dividing cells and affect a particular phase of cell division

3. Agents that affect all or most of the phases of the cell cycle (Box 32-2)

Box 32-2 Cancer Chemotherapy Agents

Direct DNA-Interacting Agents	Indirect DNA-Interacting Agents
Alkylators Cyclophosphamide Chlorambucil Melphalan BCNU (carmustine) CCNU (lomustine) Ifosfamide Procarbazine Cisplatin Carboplatin	Antimetabolites Deoxycoformycin 6-Mercaptopurine 2-Chlorodeoxyadenosine Hydroxyurea Methotrexate 5-Fluorouracil (5-FU) Cytosine arabinoside (ARA-C) Gemcitabine Fludarabine phosphate Asparaginase
Antitumor Antibiotics Bleomycin Actinomycin D Mithramycin Mitomycin C Etoposide (VP-16) Topotecan Doxorubicin and daunorubicin Idarubicin Mitoxantrone	Antimitotic Agents Vincristine Vinblastine Paclitaxel Estramustine phosphate

Whatever the mode of action of these drugs, they destroy malignant cells in the same proportion of cells that is killed for each dose of chemotherapeutic agent.

Alkylating Agents, Antimetabolites, and Alkaloids

The first chemotherapeutic agents to be used in bone marrow transplantation were alkylating agents such as cyclophosphamide and busulfan. Their common mechanism of action is that on entering the cells, the alkyl groups bind to the electrophilic sites in DNA and other biologically active molecules. This bifunctional alkylation of DNA results in efficient cross-linking of the DNA, leading to strand breakage and ultimately cell death.

Antimetabolites such as 5-fluorouracil (5-FU), cytarabine, and fludarabine induce cytotoxicity by serving as false substrates in biochemical pathways. Many are nucleoside analogues that are incorporated into DNA and RNA and therefore inhibit nucleic acid synthesis. They are cell cycle active and are specific mainly for cells in the S phase.

The vinca alkaloids, vincristine and vinblastine, which were isolated from the periwinkle plant, inhibit microtubule assembly by binding to tubulin. This microtubule stabilization prevents the cells from dividing; thus these alkaloids are cytotoxic predominantly during the M phase of the cell cycle. Bleomycin, an antitumor antibiotic, induces single-strand and double-strand breaks through free radical generation and is cytotoxic mainly during the G2 and M phases of the cell cycle.

Radiotherapy

Radiotherapy uses large doses of high-energy beams or particles to destroy cancer cells in a specifically targeted area. Radiation damages DNA and keeps the cells from dividing.

Radiotherapy is most often used on localized solid tumors and on cancers such as leukemia and lymphoma that affect the bloodstream. More than 50% of patients with cancer undergo radiation therapy; for some, it will be the only cancer treatment that they need. Radiation is often used in combination with other treatments to shrink the tumor or make surgery or chemotherapy more effective. Used after chemotherapy or surgery, radiation destroys any cancer cells that might remain. Normal cells that may be affected by radiotherapy will usually repair themselves.

Evaluation of Candidates for Peripheral Blood Stem Cell and Bone Marrow Transplantation

Factors that influence the eligibility for bone marrow transplantation include age, disease status, performance status for the recipient, organ function (i.e., heart, lung, liver, and kidney function), infectious disease status, compatibility of the donor and recipient, and psychosocial status. Patients who undergo high-dose chemotherapy and hematopoietic stem cell transplantation require a careful evaluation of all body systems to ensure that they are able to tolerate the aggressive therapy and the isolation of their hospital stay, which can last days to months.

Pretransplantation evaluation and testing (Fig. 32-1) may include HLA tissue typing, bone marrow biopsy and aspiration, electrocardiography, echocardiography, complete history and physical examination, chest x-ray study, pulmonary function tests, dental cleaning, blood tests such as complete blood count (CBC) and blood chemistries, and screening for viruses such as hepatitis, human T lymphotropic virus I and II, cytomegalovirus (CMV), herpes, and human immunodeficiency virus (HIV).