News Release

Hope available for patients with anemia and myelodysplastic syndrome

Peer-Reviewed Publication

American Society of Hematology

(San Diego, Calif., December 8, 2003) – Several studies presented during the 45th Annual Meeting of the American Society of Hematology (ASH) provide hope for patients with red blood cell diseases in the form of potential new treatments, as well as guidance for health care providers in caring for patients.

Anemia is a disease in which the blood lacks adequate healthy red blood cells to carry appropriate levels of oxygen to patients' tissues, making them feel tired. Many types of anemia exist, each with its own cause, such as an iron or vitamin deficiency, blood loss, chronic illness, a genetic or acquired defect or disease, or a medication side effect. Anemia can be temporary or long-term and can range from mild to severe. Anemia affects more than three million Americans, making it the most common blood disorder in the United States. Women and people with chronic diseases are at increased risk for the condition.

A related disease is myelodysplastic syndrome, a disease that in mild cases may present primarily as anemia. Myelodysplastic syndrome (MDS) is characterized by abnormal blood-forming cells of the bone marrow, which produce too few red blood cells, white blood cells, and platelets. The bone marrow is unable to produce blood cells effectively, and many of the formed cells are abnormal or defective. The abnormal cells are usually destroyed before they leave the bone marrow or shortly after they enter the bloodstream. As a result, patients experience a shortage of blood cells, which is reflected in their low blood counts. MDS may be a form of cancer, according to most hematologists, since it is considered a clonal disease with a single population of abnormal cells.

"These blood disorders are not simply quality of life diseases, but carry with them serious health concerns that may endanger patients' lives," said Stanley Schrier, M.D., President-Elect of the American Society of Hematology. "Research such as that presented during the ASH annual meeting helps provide hope for patients and guidance for investigators in the treatment of these diseases."

Late-Life Anemia Identifies Persons at Risk for Mortality and Hospitalization (Abstract 881)

Anemia is common in old age and has been shown to affect the physical function of elderly adults. Researchers from Wake Forest University School of Medicine, Winston-Salem, N.C., conducted a study to more fully identify the detrimental health effects of anemia and found that elderly people with anemia had increased chances of death and hospital stays.

"These findings indicate that late-life anemia characterizes persons at risk for important clinical health outcomes," said Brenda W. Penninx, Ph.D., of the Wake Forest University, lead author of the study. "Health care professionals need to be aware of the clinical implications of anemia and begin to regularly test their patients for the disease."

Researchers used data from three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), a National Institute on Aging-sponsored study on aging. A total of 3,607 subjects, aged 71 years of age and older, provided blood samples that were used to measure hemoglobin (Hb, an iron-containing respiratory pigment of red blood cells that functions primarily in the transport of oxygen from the lungs to the tissues of the body). Anemia was defined as Hb<12 g/dL in women and Hb<13 g/dL in men. Data on mortality and hospital admissions over a four-year period were obtained from death records and the Health Care Financing Administration (HCFA) Medicare database.

Anemia was identified in 12.5 percent of the patients. During the four-year follow-up period, anemic persons were more likely to die than non-anemic persons (37 percent versus 22.1 percent). These patients were also hospitalized more often (65.9 percent versus 54.6 percent) and spent more days in the hospital (25 versus 13.7 days). After excluding persons with baseline presence of heart disease, diabetes, stroke, cancer, infectious disease, lung disease, and kidney disease, anemia remained significantly associated with increased risks of mortality and hospitalization.

Efficacy and Safety of CC5013 for Treatment of Anemia in Patients with Myelodysplastic Syndromes (MDS) (Abstract 641)

Effective management for myelodysplastic syndrome is limited, but a study presented by researchers at the Arizona Cancer Center, Tucson, Ariz., indicates that a new drug, CC5013, may have unprecedented activity in patients who were not successfully treated with conventional therapy.

"The ineffective production of red blood cells as a result of premature cell death represents the hallmark of myelodysplastic syndromes for which effective management is limited," said Alan List, M.D., lead author of the study, formerly of the Arizona Cancer Center, and now leader of the Hematologic Malignancies Program at the H. Lee Moffitt Cancer Center. "CC5013 has novel pharmacologic effects that converge upon survival signals in cancer cells particularly important in MDS."

CC5013 is an analog of thalidomide that does not have the neurological toxicities associated with the parent compound. Its novel mechanisms promote heterotypic (different in kind) adhesion and cell cycle arrest, sensitization to death-receptor induced programmed cell death, abrogation (abolishment) of cellular response to receptor-initiated mutations signals, and suppression of inflammatory cytokine (a class of immunoregulatory proteins secreted by cells) generation.

Results showed that 21 patients, or 64 percent, experienced a positive or erythroid (red blood cell) response, including major responses (i.e., transfusion independence) in 20 patients. Major cytogenetic, or cellular, responses were seen in 11 patients, including restoration of normal karyotype (chromosomal cellular characteristics) in 10 patients. Responses were clinically meaningful (median hemoglobin rise = 5.15 g/dl; range, 2.8-9.64 g/dl) and durable (TTF not reached at more than 38 weeks; range 19 to >75 weeks), with maintenance hemoglobin in near normal range (mean Hgb plateau, 12.9 g/dl; range 11.1 – 15.7 g/dl). Hematologic improvement was associated with resolution of megakaryocytic dysplasia (the abnormal appearance of bone marrow cells that are the source of platelets), whereas reduction in bone marrow blast percentage (three out of six) or RS was less common (one out of 10). Bone marrow proliferative index was decreased 40 percent accompanied by a reduction in bone marrow microvessel (a blood vessel of the microcirculatory system) density in responding patients.

The most common side effect was grade 3 or higher dose-dependent myelosuppression suppression of the bone marrow's production of blood cells and platelets; 25 mg = 90 percent; 10 mg daily = 61 percent; 10 mg scheduled = 47 percent). Other grade 1 or 2 side effects included scalp pruritus (localized or generalized itching due to irritation of sensory nerve endings) that resolved itself, diarrhea, transient urticaria (hives), and hypothyroidism in two patients. Researchers treated 45 patients, median age 72, who had red blood cell transfusion-dependent disease or symptomatic anemia. Each patient received treatment with one of three CC5013 oral dose schedules, 25 mg or 10 mg daily, or 10 mg daily for 21 days every four weeks. Drug tolerance was evaluated at four-week intervals with response assessment according to the International Working Group (IWG) criteria after eight and 16 weeks of treatment. Thirty-six patients could be evaluated for response after completing eight weeks or more of study treatment. Ten of the patients, or 28 percent of the study sample, had previously been unsuccessfully treated with thalidomide, and 28 patients, or 78 percent, had not successfully been treated with erythropoietin.

Approximately 30 percent of MDS cases progress into acute leukemia, a rapidly growing bone marrow cancer.

Tipifarnib (Zarnestra) in Previously Untreated Poor-Risk AML and MDS: Interim Results of a Phase 2 Trial (Abstract 613)

A phase II trial of a non-peptidomimetic agent, tipifarnib, shows that the drug has activity in previously untreated poor-risk acute myeloid leukemia (AML) and myelodysplastic syndrome, with a relatively low rate of serious side effects, according to data presented by researchers at the University of Rochester, Rochester, N.Y. Tipifarnib is a member of a novel class of anti-cancer agents, farnesyltransferase inhibitors (FTI), that selectively inhibit farnesyltransferase, an enzyme responsible for the posttranslational modification of several proteins including Ras. Since Ras is among the most commonly mutated oncogenes associated with cancer, this class of drugs has been evaluated in clinical trials in a diversity of tumors.

"We are encouraged by the results of our trial with tipifarnib, and are looking forward to conducting further studies to confirm the effects of the drug, both as a single agent and in combination," said Jeffrey E. Lancet, of the University of Rochester, lead author of the study.

"In addition, we think that further studies may also identify potential mechanisms of resistance as well as to serve as predictors of response to tipifarnib."

This study primarily enrolled older patients, the median age being 74. Twenty-one percent of patients have experienced a complete response, and the overall response rate (complete response and partial response) was 36 percent. Median duration of response in complete responders was 5.3 months (range 1 to more than 13 months). The median overall survival is 5.7 months for all patients. In patients experiencing a complete response, the median overall survival is 18 months. Treatment-related deaths occurred in seven percent of patients. Grade 3 – 4 non-hematologic toxicities occurred in 77 of 103 patients (77 percent), largely comprised of infection or fever associated with neutropenia (decrease in white blood cells).

A total of 103 patients have been enrolled in the multi-center clinical trial of previously untreated patients with high-risk acute myeloid leukemia and myelodysplastic syndrome (MDS); 98 patients are evaluable for response. Patients were administered 600 mg of tipifarnib twice a day for 21 days, followed by a one- to three-week recovery period. Up to four cycles of tipifarnib were permitted in patients with complete responses.

Poor-risk AML is defined in many ways, such as arising from myelodysplastic syndromes, therapy-related AML in patients 60 years of age or over (in absence of favorable cytogenetics), adverse cytogenetics, or other blood conditions. Acute myeloid leukemia is a disease in which cancer cells are found in the blood and bone marrow. AML causes arrest and overgrowth of immature cells (blasts) in the bone marrow that would otherwise normally develop into mature blood cells. These immature blast cells are found in high numbers in the blood and the bone marrow, leading to suppression of normal blood cell development and function.


The American Society of Hematology is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.

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