Rare Hematologic Disorders: Uncommon Lymphoproliferative Disorders

Lymphoproliferative disorders are those in which lymphocytes, white blood cells produced in the lymphatic tissue (the lymph nodes, spleen, thymus, for example), are over-produced or act abnormally. Lymphocytes include T cells, which help control the body's immune reactions, and B cells, which produce antibodies to fight infection. These cells circulate in the blood and lymphatic system, and participate in the body's direct attack against foreign invaders.

LGL Leukemia

Large granular lymphocytic (LGL) leukemia is a chronic leukemia of T lymphocytes — white blood cells that originate in the lymph system and in the bone marrow, and that help fight infection. Rarely, LGL leukemia is a disease of natural killer cells, which are lymphocytes that normally attack tumor cells. The disease usually affects people in their sixties. Symptoms include anemia, low levels of platelets and infection-fighting neutrophils in the blood (conditions called, respectively, thrombocytopenia and neutropenia), and an enlarged spleen. Doctors diagnose this disease through a biopsy of the bone marrow, or by using flow cytometric analysis of the circulating blood or bone marrow cells, a procedure in which various types of blood or bone marrow cells are separated, identified, and counted. Treatment usually involves chemotherapy, sometimes granulocyte-colony stimulating factor (G-CSF), and possibly surgery to remove the spleen. A closely related T-lymphocyte disorder is called T gamma disease; it is essentially the same as LGL leukemia.

T-cell chronic leukemia is an older diagnostic term used to describe a number of different diseases including LGL leukemia and T-cell lymphomas. Analysis of the blood or bone marrow by flow cytometry or special staining of the biopsied tissue often leads to a more precise diagnosis.

Cutaneous T-Cell Lymphomas

In patients with cutaneous T-cell lymphoma (CTCL), the skin is infiltrated with T lymphocytes. CTCL can develop over many years. Early symptoms include itchy, dry, and scaly skin; as the disease progresses, tumors (or nodules) may form on the skin and can spread to the lymph nodes and other organs. CTCL manifests itself in a variety of forms. When large numbers of tumor cells are found in the blood, the condition is called Sézary syndrome. Mycosis fungoides is a very slow-growing and chronic type of CTCL, which can also develop into Sézary syndrome. As with CTCL, symptoms of mycosis fungoides include a red, generally itchy skin rash, which is sometimes nodular or bumpy in appearance. Physicians diagnose CTCL using a biopsy of the affected tissue. Treatment depends on the stage and form of the disease but may include radiation therapy, chemotherapy, and phototherapy, a treatment that uses light and drugs that make the cancer cells more sensitive to light. Physicians may also treat CTCL with biological therapy (also called immunotherapy) and with drugs related to vitamin A (retinoids).

Hairy Cell Leukemia

Hairy cell leukemia, a chronic form of leukemia, is a cancer of B lymphocytes, cells that make antibodies to help fight infection; these cells have projections (they look like hairs) and they are found in the blood, bone marrow, and spleen. Patients with this disease usually have low blood counts, an enlarged spleen, sometimes develop unusual kinds of infections, and may experience fatigue, weakness, and abdominal discomfort due to the enlarged spleen. Their levels of white blood cells, red blood cells, and platelets may be reduced, and “hairy cells” (named for the many irregular villi found in the affected cells) may or may not be present in the blood. Because of the disease, physicians may have trouble obtaining a sample of bone marrow using a technique called a bone marrow aspirate (this is called a “dry tap”), but a biopsy should show the presence of the hairy cells. Current treatments are very effective, particularly 2-chlorodeoxyadenosine (2-CDA); other effective treatment options include deoxycoformicin (DCF), interferon, and surgery to remove the spleen.

Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is an aggressive type of non-Hodgkin's lymphoma that generally occurs in middle-aged and elderly people and is becoming increasingly recognized. MCL is a disease of B lymphocytes — cells that make antibodies to help fight infection — and is typically found in the lymph nodes, spleen, bone marrow, or blood; it is often diagnosed at an advanced stage.

Although MCL usually responds to standard chemotherapy, progression-free survival is typically 16-28 months.⁽¹⁾ At Memorial Sloan-Kettering, however, researchers discovered that using a different dosing schedule of chemotherapy followed by stem cell transplant has better results. In a study published in 2010, patients treated with this approach had median progression-free survival of 5 years.⁽²⁾ Monoclonal antibody-based treatments are being studied here as well.

Waldenström's Macroglobulinemia

Waldenström's macroglobulinemia is a type of lymphoma that affects the B lymphocytes. In this disease, B lymphocytes increase in number and occupy the bone marrow, lymph nodes, and spleen. These cells make a protein called immunoglobulin M (IgM), which can accumulate in the blood, increasing its thickness. The disease usually affects people over the age of 60. Symptoms may include weakness, fatigue, headaches, bleeding, and enlargement of the lymph nodes and spleen. Treatment includes chemotherapy and, if a patient's IgM level is very high, physicians can remove the protein from the blood using a procedure called plasmapheresis.