Understand Childhood Cancers and Blood Disorders
Stem Cell Transplant
Many malignant diseases show better responses to treatment when the doses of the chemotherapy are given at higher doses. While at times side effects, such as heart dysfunction or potential nerve damage, make such an approach untenable, for many drugs the limiting factor is the effects on blood counts. With many medications, the anti-cancer effects increase as the doses of the medications are raised, but the suppression of blood counts lasts longer, placing the patient at greater risk for serious bleeding or life-threatening infections. At times, combinations of chemotherapy and radiation can have such a prolonged and profound effect on the bone marrow that it becomes permanently incapable of producing blood cells, a serious condition called aplastic anemia.
As a way of overcoming this obstacle, an approach has been developed over the years to supply what are known as hematopoietic stem cells for these patients. These stem cells, which predominantly inhabit the bone marrow but also circulate in the blood stream, are capable of differentiating and ultimately producing all of the blood cells found in the body. They need only be infused into a patient’s blood stream, like a transfusion, and the stem cells then “home in” on the bone marrow where they then reproduce and differentiate. Originally only collected from donor bone marrows, stem cells now can be collected from the blood stream as well. This has made the process of providing stem cells for patients much easier, without any need for painful procedures or anesthesia. Another rich source of stem cells is the placenta following delivery of babies. The result of these different collection techniques is an enlarging “bank” of stem cells and international registries providing information on millions of potential donors of stem cells. This has now opened up a therapeutic approach with stem cell transplants for a whole vista of diseases, including many non-malignant conditions.
Prior to beginning any transplant consideration, a suitable match must be found. The first transplants were done with identical twins providing the stem cells. With the advent of Human Lymphocyte Antigen (HLA) typing, the donor pool has broadened considerably. Most perfect matches are provided by siblings of the patients but, with the growing international registries, HLA-matched unrelated donors can be located for many patients. In situations where a perfect match cannot be identified, partial mismatched donors can often be used.
HLA matching is important for two reasons. In the absence of a good match, the donated cells can be rejected by the body, resulting in a patient who cannot produce blood cells. The other problem that arises, even with very good matches, is a condition known as graft versus host disease (GVHD). In this situation, the engrafted foreign cells identify the host patient as something foreign, and begin to attack the body. Signs of acute GVHD included rashes, severe diarrhea, liver dysfunction, and falling blood counts. GVHD can also occur in a chronic form, with dry, leathery skin, liver dysfunction, low blood counts, and lung damage. GVHD can be severe and lethal, and must be treated with immunosuppressive medications.
Stem cell transplants are now commonly used for a variety of malignant and non-malignant conditions. Transplants are part of front line therapy for children with acute nonlymphoblastic leukemia and chronic myelogenous leukemia. They are considered for relapsed lymphoblastic leukemia, for some very high risk newly diagnosed acute lymphoblastic leukemias, and for many recurrent lymphomas or germ cell tumors. The data for many solid tumors is not as clear, but transplants have been shown to be of value in infants with certain types of brain tumors to avoid using high dose radiation with its severe long-term adverse effects.
Many nonmalignant conditions have utilized stem cell transplants, since some of the marrow cells differentiate into other cells that produce necessary enzymes that can correct a variety of inherited disorders. Transplants already have an established record for sickle cell disease and thalassemias, red blood cell disorders that entail serious long-term problems and can be cured with transplants. Osteopetrosis, a disorder characterized by a crowding out of the bone marrow space with bone tissue, can be cured with stem cell transplant that provides normal osteoclasts that are missing. Transplant is the treatment of choice for Wiskott-Aldrich Syndrome, an inherited disorder characterized by severe immunodeficiency and low platelet counts. Other storage disorders, such as the mucopolysaccharidoses, have also been cured with bone marrow transplant.