Disease Focus

Numerous fusion toxins have shown efficacy in clinical trials against hematologic malignancies. Leukemias and lymphomas have been the focus of fusion toxins for decades due to their highly specific surface receptors, relative ease of diagnosis and monitoring, and accessibility to circulating recombinant drugs.  In the last few years complete remissions have been reported in several clinical trials.  The next challenges will be sustaining these responses over time and extending this success to as many cancers as possible via the engineering of new and improved fusion toxins.  Below, the major classes of hematologic malignancies are briefly described.


 
Hematological Malignancies

There are three broad categories of blood cancers: lymphomas, leukemias, and myelomas.  All three cancers derive from white blood cells.

Lymphomas typically derive from lymphocytes and originate in lymphoid tissues, such as lymph nodes, although they may subsequently diffuse into the blood and spread to non-lymphoid tissues as well.  Hodgkin lymphoma is distinct from the other lymphomas in that it involves a distinctive cell known as a Reed-Sternberg cell.  The other lymphomas, collectively referred to as non-Hodgkin lymphomas (NHLs), may involve B lymphocytes (B-NHL) or T lymphocytes (T-NHL).  Approximately 66,000 Americans will be diagnosed with lymphoma this year.  Although the incidence for lymphoma increases with age, the number of children diagnosed each year is sufficiently high that lymphoma represents the third most common cancer in children, behind leukemia and cancers of the nervous system.  Today, over 500,000 people live with lymphoma in the United States.  While Hodgkin lymphoma has seen the most dramatic advances in treatment, such that it is now considered the most curable form of cancer, there have been significant advances in treatment of most of the non-Hodgkin lymphomas as well.

Cutaneous T-cell lymphomas (CTCLs), a relatively rare and heterogenous group of T-NHLs, are characterized by atypical, skin-homing T lymphocytes.  Mycosis fungoides (MF) is the most common type of CTCL.  The name comes from the mushroom-like skin tumors noted in the first patient diagnosed.  SÚzary syndrome is a related, but more aggressive form of CTCL, with widespread skin effects and the presence of malignant lymphocytes in the blood.  Ontak® has shown efficacy in treating CTCL and is currently in clinical trials for other cancer indications as well.

Among the B-NHLs, mantle cell lymphoma (MCL) is the most aggressive, with a mean survival of about 3 years.  The incidence of MCL represents about 6% of all non-Hodgkin lymphomas (NHLs), or about 4000 new cases per year in the United States.  Because MCL is typically well advanced by the time it is diagnosed, and because its progression is often rapid, aggressive treatment regimens, typically combinations of chemotherapeutics, are generally recommended.  Frequently, physicians are combining these chemotherapeutic regimens with a monoclonal antibody, Rituxan®, which has been effective in prolonging survival in several other types of B cell lymphomas.  The effect of these various regimens to date has largely been to prolong survival rather than to effect cures.

Leukemias may also derive from lymphocytes or may derive from other white blood cells, such as neutrophils.  The primary distinction between leukemias and lymphomas is that leukemias derive from the bone marrow, although they may subsequently spread to the lymph nodes.  The leukemias are broadly divided into lymphoid vs. myeloid, depicting the cell of origin, and further divided into chronic and acute forms.  Thus, the four primary types of leukemia are chronic and acute lymphoid leukemia (CLL and ALL) and chronic and acute myeloid leukemia (CML and AML).  ALL is most prevalent in young children, while CLL, CML, and AML are most prevalent in adults over the age of 50.  There are currently about 200,000 people living with leukemia in the United States.  The last 40 years has seen steady progress in the battle against leukemia such that cures are now common.  Strikingly, over half of all ALL patients diagnosed prior to age 15 are now cured.

Myelomas involve the plasma cell, a type of cell that derives from B lymphocytes.  Plasma cells are the cells that secrete antibodies.  Thus, myelomas are diagnosed by the superabundance of one or several species of antibody in the circulation.  About 16,000 people are diagnosed each year in the U.S. and about 60,000 currently have the disease.  The median age of onset is 70 and diagnoses earlier than age 45 are extremely rare.


----------------------------------------------------------------------------------------------------------

Further Reading

The Leukemia and Lymphoma Society provides a wealth of information on leukemia, lymphoma, and myeloma as well as support for patients.
http://www.leukemia-lymphoma.org/hm_lls

The Lymphoma Research Foundation focuses on advancing research for lymphoma.
http://www.lymphoma.org

Recently, the LRF has launched a new site devoted to Mantle Cell Lymphoma.
http://www.mantlecelllymphoma.org