Myeloproliferative Disorders

Myeloproliferative disorders are a group of blood diseases characterized by chronic increases in some or all of the blood cells. This group of blood disorders includes

Polycythemia vera
Essential (or primary) thrombocythemia
Idiopathic myelofibrosis
All blood cells start out as hemopoietic (blood-forming) stem cells with the potential to become red cells, white cells, or platelets. Myeloproliferative disorders begin with a change to the DNA of a single stem cell in the marrow, where blood cells are made.

Polycythemia vera is a disease in which the red cells are the main cells that are increased beyond normal levels. In many patients, white blood cell and platelets counts are also elevated.

Complications result mainly from the increase in red cells and in platelets: too many red blood cells make it difficult for the blood to flow smoothly; too many platelets can lead to the formation of blood clots; and underlying vascular disease, commonly found in older people, can increase the risk of serious complications, such as strokes or heart attacks.

Essential (or primary) thrombocythemia is a disease in which the platelets are the main cells that are increased beyond normal levels.

The normal formation of platelets consists of stem cells forming a few very large cells in the marrow called megakaryocytes. Each of the megakaryocytes generates hundreds or thousands of platelets. In essential thrombocythemia, the altered stem cells produce an excessive number of megakaryocytes. The end result is abnormally high levels of platelets in the blood. When present in very large numbers, these platelets may not function normally and can cause blockages in blood vessels or bleeding problems.

Idiopathic myelofibrosis is a disease in which scar-like tissue forms in the marrow as a result of abnormal production of red cells, white cells, and platelets.

Too few red cells are made, and usually too many white cells and megakaryocytes. The excessive production of megakaryocytes leads to abnormally high levels of platelets in the blood. The overproduction of abnormal megakaryocytes also releases chemicals in the marrow that lead to the production of fibrous (scar-like) tissue in the marrow.

White Race Increases Hypothyroidism Risk after Hodgkin Lymphoma Treatment

By Will Boggs, MD

NEW YORK (Reuters Health) - White patients face a higher risk than black patients for becoming hypothyroid after neck irradiation for pediatric Hodgkin's lymphoma, according to a report in the April 1st Journal of Clinical Oncology.

"This article should remind any physician taking care of Hodgkin survivors that hypothyroidism is a common side effect of radiation therapy to the neck and chest, and that a high level of suspicion is warranted especially in white patients," Dr. Monika L. Metzger from St. Jude Children's Research Hospital, Memphis, Tennessee told Reuters Health.

In response to an earlier report suggesting that white race is a risk factor for hypothyroidism in adults who undergo head and neck irradiation, Dr. Metzger and colleagues investigated the possibility further in a study of 461 survivors of pediatric Hodgkin's lymphoma -- 338 whites, 73 blacks.

Hypothyroidism developed in a significantly higher percentage of white patients (47%) than black patients (21%), the authors report, after a median of 2.9 years.

The estimated cumulative incidence of hypothyroidism at 20 years was also significantly higher for white patients (52%) than for black patients (23%), the results indicate, and after adjustment for other risk factors the risk of hypothyroidism was 2.5 times higher in whites than blacks.

Radiation dose also affected the incidence of hypothyroidism, the researchers note. Less than a third (30%) of patients who received 21 Gy or less of radiation to the thyroid would be expected to develop hypothyroidism over the ensuing 20 years, but 61% of patients who received more than 21 Gy would be expected to become hypothyroid.

Combining race and dose, hypothyroidism occurred within 20 years in 65% of white patients who received more than 21 Gy of radiation, compared with only 36% of black patients.

"It appears that the racial differences for hypothyroidism are related to different genetic make up, as several endocrinopathies favor different races," Dr. Metzger said. "Nonetheless, it would be interesting to see whether white and black patients have different tolerance to radiation therapy. This is something we would like to study."

"Every pediatric Hodgkin lymphoma survivor merits regular thyroid function screening after radiation to the neck and chest, regardless of race," Dr. Metzger advised. "Patients who develop signs and symptoms suggestive of hypothyroidism (weight gain, depression, cold intolerance, and fatigue) should be screened at the time of symptom onset, since treatment for hypothyroidism is simple and cheap, and delayed diagnosis can have significant negative impact on quality of life."

Atypical Lymphoid Tissue Lymphoma May Respond to Antibiotics

NEW YORK (Reuters Health) - Antibiotic treatment may be effective for patients with early stage gastric mucosa associated lymphoid tissue (MALT) lymphoma, but are negative for Helicobacter pylori, Austrian researchers report in the May issue of Gut.

In most patients, MALT is associated with H. pylori infection, Dr. Markus Raderer of the Medical University Vienna and colleagues report. This has led to the use of antibiotics to eradicate the pathogen and to obtain generally good results.

The researchers determined if this approach could be effective in H. pylori-negative patients with MALT lymphoma restricted to the stomach. Six patients were treated with clarithromycin, metronidazole and pantoprazole.

After 3 to 9 months of treatment, five of the six patients showed lymphoma regression. There were four complete responses and one partial remission. The remaining patient had stable disease and was referred for chemotherapy at 12 months.

Follow-up at 19 months showed that all patients were alive and four continued to have a complete response.

"These findings," Dr. Raderer told Reuters Health, "might point to as yet undetected bacterial agents or additional immunological findings in the antibiotics used which have not been elucidated so far."

Nevertheless, given these results, he concluded that "H pylori-negative patients with stage I MALT lymphoma should have the chance of initial treatment with antibiotics."

Polio Vaccine Not Tied to Non-Hodgkin Lymphoma

NEW YORK (Reuters Health) - Norwegian researchers report finding no support for the proposed link between a polio vaccine possibly contaminated with simian virus 40 (SV40) and lymphoproliferative diseases, including non-Hodgkin's lymphoma (NHL) and excluding Hodgkin's lymphoma.

The vaccine was administered between 1955 and 1963 around the world. Dr. Guri Olsen Thu and colleagues at the Cancer Registry of Norway, Montebello, Oslo, investigated the proposed link between vaccine and NHL by examining Norwegian cancer incidence data, looking at birth cohorts that the researchers assumed received the vaccine in question.

Between 1953 and 1997, the incidence of lymphoproliferative diseases tripled for both males and females. This increase was primarily due to an increase in cases of NHL.

Dr. Thu's group analyzed the data according to age, cohort and time period. "The cohort effect was more prominent than the period effect," they report in the April 15th International Journal of Cancer.

"However," the investigators conclude that "the variations in incidence patterns across the birth cohorts did not fit with the trends that would be expected if a SV40-contaminated vaccine did play a causative role" in the increase in lymphoproliferative diseases.

Int J Cancer 2006;118:2035-2039.

Hairy Cell Leukemia

Hairy cell leukemia is a type of chronic lymphocytic leukemia (CLL). CLL is one of the four major categories of leukemia. Based on the category and subset, the physician can determine what treatment will work best for the patient. Hairy cell leukemia is a slow-growing malignant disorder that affects white blood cells called lymphocytes. The disease is called hairy cell leukemia because the leukemic lymphocytes have short, thin projections from their surface that look like hairs when examined under a microscope. The hairy cells accumulate in the bone marrow and spleen and to a lesser extent in lymph nodes. The accumulation of these functionless leukemic lymphocytes in the marrow prevents the production of normal blood cells by the marrow. These normal cells are of great importance to the well-being of the patient. Researchers do not understand the ways in which leukemic cells get their competitive advantage, overgrow the marrow and prevent normal cells from being made.

Causes and Risk Factors
The cause of hairy cell leukemia and the means to prevent it are unknown. There seems to be no direct link between the disease and exposure to environmental toxins. The disease has very occasionally occurred in members of the same family. However, no hereditary pattern has been established.

Symptoms and Signs
Hairy cell leukemia may be difficult to diagnose early because its symptoms are vague and resemble those of other illnesses. The disease may be discovered during a medical evaluation because of an enlarged spleen or an unexpected decrease in normal blood cell counts. Patients may experience a feeling of discomfort or fullness in the upper left side of their abdomen as a result of the enlarged spleen. Unexplained weight loss and loss of a sense of well-being may bring patients to their physician.

Hairy cells accumulate in the bone marrow preventing the marrow from producing sufficient normal blood cells. The disruption of normal blood cell production leads to anemia (deficiency of red cells), thrombocytopenia (deficiency of platelets) and increased risk of infection (deficiency of white cells called neutrophils and monocytes which fight infection). Often all three blood cell types are deficient (referred to as pancytopenia). Although the hairy cells are abnormal types of lymphocytes, enlargement of lymph nodes is uncommon. Hairy cells accumulate in the marrow and spleen (probably where these cells grow best), but less so in the lymph nodes.

A marked decrease in phagocytes (neutrophils and monocytes) results in an increased chance of developing an infection. Some patients are first aware of the disease because of fever, chills, and other signs of infection. Black and blue marks, as a result of the low concentration of blood platelets, may occur on the skin without injury or after a minor injury.

Approach to Diagnosis

Medical history and physical examination
Complete blood counts
Bone marrow examination
Immunophenotyping
An accurate diagnosis is made by an evaluation of the cells in the blood and marrow. A physician may suspect hairy cell leukemia after performing a preliminary examination of the blood. The normal blood cell counts are low and there may be hairy cells detected in the blood. Occasionally, the hairy cells are numerous in the blood, resulting in an increase in the white cell counts. A bone marrow sample is often needed to confirm the disease. Obtaining a marrow sample from the hipbone can be done in a physician's office.


Special testing, called immunophenotyping, is also performed on the blood and marrow cells. Certain proteins are located on the surface of cells. Each type of cell has its own characteristic pattern of these proteins. Like other cells, hairy cells have a pattern that helps in their identification. Examination of these surface proteins (antigens) with antibodies that combine with their specific antigens and light up using special detection equipment, helps the doctor confirm the type of leukemia that is present. This method also helps to subclassify cell types, which may, in turn, help to decide on the best treatment to apply in that type of leukemia or lymphoma. The antigen on a cell is referred to as cluster of differentiation or "CD" with an associated number. For example, CD11c, 22, and 256 may be present on leukemic hairy cells.

Other tests include a computed tomography (CT) scan which uses multiple images in the computer to create a two dimensional image of the body at several levels. This is a technique for imaging body tissues and organs. The resulting images are displayed as a cross-section of the body at any level from the head to the feet. A CT scan of the chest or abdomen permits detection of an enlarged lymph node, liver or spleen. A CT scan can be used to measure the size of these and other structures during and after treatment. Use of the CT scan for staging enables the physician to determine the extent of enlarged nodes and other organ involvement in the thorax or abdomen. CT scans are more sensitive than x-rays in finding tumors. These studies can be repeated after treatment to determine if the abdominal lymph node or spleen enlargement has decreased or returned to normal size.