Emerging Paradigms in the Management of Leukemias and Lymphomas
Amy Hatfield, PharmD, BCOP,* and MiKaela Olsen, RN, MS†
Leukemia, lymphoma, and multiple myeloma, collectively called hematologic malignancies, are all cancers of blood-forming organs. These diseases arise due to errors in the genetic information contained in immature blood cells. As a consequence of these errors, cell development is arrested so that rather than maturing, abnormal blood cells–primarily of the leukocyte (white blood cell or WBC) lineage–proliferate in an unregulated manner. Nearly every stage of blood cell development (ie, hematopoiesis) can give rise to a distinct type of hematologic malignancy. The common ground between different hematologic malignancies is improper or aberrant differentiation of blood cells and/or their precursors. In leukemia, cancerous leukocytes are found circulating in the blood and bone marrow, whereas in lymphoma, the cells tend to aggregate and form masses, or tumors, in lymphatic tissues. Multiple myeloma is characterized by the proliferation of a specific subset of WBCs called plasma cells, which release aberrant proteins into the blood and urine. Despite their similarities, the types of hematologic malignancies are also quite distinct, and vary significantly in their causes, molecular profiles, and natural progression.
In patients with leukemia, hematopoietic cells remain morphologically or functionally immature and multiply continuously, eventually crowding out healthy cells and thereby preventing normal development of WBCs, erythrocytes (red blood cells), and thrombocytes (platelets). The major types of leukemia are classified according to 2 parameters: onset/duration and predominant type of proliferating malignant cell. Leukemias can be either acute (having a sudden onset and rapidly intensifying from early signs and symptoms) or chronic (developing slowly, with signs and symptoms sometimes not appearing for years) and either lymphocytic (characterized by proliferation of aberrant lymphocytes) or myelogenous (characterized by proliferation of aberrant nonlymphocytic blood cells). Thus, the 4 major types of leukemia are acute lymphocytic leukemia, acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia. These different types of leukemia have unique causes and affect different subpopulations (eg, some leukemias are more common in children whereas others primarily affect the elderly), and are therefore treated with distinct combinations of chemotherapeutic agents, targeted therapies, and other treatment modalities.
The lymphomas are a large group of cancers originating in lymphoid tissue. Hodgkin's lymphoma (or Hodgkin's disease) is a specific type of lymphoma named after the physician who first described it, Thomas Hodgkin; all other lymphomas are collectively called non-Hodgkin's lymphoma (NHL). There are at least 30 types of NHL, each of which is sensitive to different types of therapy. Although multiple myeloma is also a lymphoid malignancy and is sometimes categorized as a type of NHL, it is more commonly considered a separate entity. Myeloma is characterized by the proliferation of aberrant antibody-secreting plasma cells called myeloma cells. Whereas normal plasma cells produce and secrete the antibodies used to fight infection, myeloma cells release nonfunctional immunoglobulins, which literally clog up the bone marrow as well as other organs, such as the kidneys. As with other hematologic malignancies, a specific subset of therapies is used to treat myeloma.
Despite advances in diagnosis and treatment and improvements in patient survival, hematologic cancers continue to have a significant impact on the lives of Americans. Currently, approximately 700 000 people in the United States are living with leukemia, lymphoma, myeloma, and other blood cancers, and over 135 000 new cases are diagnosed each year (Table).1,2 Although mortality has declined and 5-year survival rates have increased among adults and children with certain forms of these diseases, an estimated 52 300 Americans will die from hematologic malignancy in 2007.2
As mentioned above, treatment of hematologic malignancies differs among the different diseases. However, common mainstays of treatment in the past few decades have been cytotoxic chemotherapy regimens and hematopoietic stem cell transplantation. In recent years, several targeted therapies have entered the hematologic malignancy treatment landscape. By directly interacting with the aberrant molecules responsible for cancer cell pathogenesis, these treatments have the potential to more effectively inhibit proliferation of aberrant cells and to be associated with less toxicity than traditional chemotherapeutic agents. Because a large proportion of the patient population with hematologic malignancy is elderly, treatment-associated toxicities are a major concern for patients as well as healthcare providers.
This issue of Johns Hopkins Advanced Studies in Medicine is based on proceedings from a roundtable held in December 2006, in Orlando, Fla, at which it was our pleasure to serve as chairs. The discussion focused on patient management issues in the treatment of a subset of hematologic malignancies from a nursing and pharmacist perspective, with particular emphasis on current and investigational therapies. This monograph was developed by all participants at the roundtable, which in addition to ourselves included Sandy Allen-Bard, RN, MSN, NPc, Connie Zanzig Augustyniak, RN, BSN, Deborah Blamble, PharmD, BCOP, Chris Fausel, PharmD, BCOP, Mollie Moran, MS, CNP, and Amy Robbins, PharmD, BCOP.
The first section of this monograph addresses AML and 2 related conditions, promyelocytic leukemia and myelodysplastic syndromes, and subsequent sections cover the lymphoid malignancies CLL, NHL, and multiple myeloma. Each of these disease sections includes a discussion of the epidemiology, classification schemes, currently used treatment regimens, investigational therapies, and patient management issues related to the disease. The monograph ends with a brief discussion of reimbursement and management issues specific to targeted therapies for hematologic malignancies.
1. Leukemia and Lymphoma Society. Understanding Drug Therapy and Managing Side Effects. Available at: http://www.leukemialymphoma.org/attachments/National/br_1095366690.pdf. Accessed January 21, 2007.
2. American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga: American Cancer Society; 2007.
*Clinical Specialist, Hematologic Malignancies, Department of Pharmacy, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland.
†Oncology and Stem Cell Transplant Clinical Nurse Specialist, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland.
Address correspondence to: Amy Hatfield, PharmD, BCOP, Clinical Specialist, Hematologic Malignancies, Department of Pharmacy, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 180, Baltimore, MD 21287-6180. E-mail: firstname.lastname@example.org.
The content in this monograph was developed with the assistance of a medical writer. Each author had final approval of his/her article and all its contents.