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MYELODYSPLASTIC SYNDROME
Also called "MDS" … "Preleukemia" … "Refractory anemia" … "Refractory dysmyelopoietic anemia" … "Smoldering leukemia"
DEFINITION: A cell multiplication disorder in which bone marrow is associated with ineffective and abnormal manufacture of bone marrow … or any of the types of blood cells derived from bone marrow.
Myelodysplastic syndrome is a group of closely related diseases (blood formation disorders). All are characterized by (1) bone marrow that does not manufacture healthy blood cells due to dysmyelopoiesis impaired maturation and (2) reduction in the number of blood cells. Abnormal blood cells are typically destroyed prior to leaving the bone marrow ... others are destroyed shortly after being released into the blood stream.
In approximately 30% of cases ... the bone marrow cells continue to multiply and acute leukemia results.
BACKGROUND: Myelodysplastic syndrome is not contagious ... it is a rare disesase that strikes people of all ages, sex, and race. Primitive blood cells called, "stem cells" react abnormally and do not reproduce new cells like itself ... or does not make offspring that can manufacture healthy blood cells.
CAUSES: (1) Some cases have been attributed to exposure to toxic chemicals. (2) Some cases are linked to radiation. (3) Some are linked to the body's reaction to a virus or infection.
In most cases ... the cause is unknown.
SYMPTOMS: Fatigue, weakness, frequent bruising, fever and recurrent infections. Without an adequate supply of blood cells, the patient develops anemia, a decreased ablity to fight infections and is at risk of uncontrollable bleeding.
THALOMID (Thalidomide) Shows Promise In Myelodysplastic Syndromes./B> Published in the August 15, 2001 issue of the journal Blood. The study, titled "Thalidomide Produces Transfusion Independence in Long-standing Refractory Anemias of Patients with Myelodysplastic Syndromes," reports on 83 MDS patients treated with Thalomid. Qty 10 transfusion-dependent patients who became transfusion independent during the study ... and 31% of evaluable patients experienced hematologic improvements.
TREATMENTS: The only known cure is an allogenic bone marrow transplant ... approximately 50% of patients transplanted with MDS will be disease free three years following a BMT. Up to 75% of patients under the age of 40 with myelodysplastic syndrome who are treated with an allogeneic stem cell transplant from an HLA-matched stem cell donor are curable.
Treatments are dependent upon individual circumstances and two primary factors ... (1) How low are the blood counts, and (2) How close the patient is to developing myeloid leukemia.
The purpose of treatments is to control the growth of the abnormal cells so the healthy ones can proliferate.
CYTOPROTECTIVE AGENTS: One hypothesis for the cause of myelodysplastic syndrome is that some patients have the abnormal production of endogenous inflammatory cytokines, which kill normal bone marrow cells. Agents that suppress the production of inflammatory cytokines include pentoxifylline and dexamethasone. Ciprofloxin is a drug that enhances the blood levels of pentoxifylline. Ethyol® is a cytoprotective agent that can improve the blood counts of patients with myelodysplastic syndrome. In a recent clinical trial, 35 patients with myelodysplastic syndrome were treated with pentoxifylline, ciprofloxacin and Ethyol® with or without dexamethasone. Seventy-six percent of patients responded with an improvement in one or more cell lines (white blood cells, red blood cells or platelets). Nineteen had an improvement in white blood cells, 11 had a 50% or more reduction in blood transfusions or improved hemoglobin level or both and 7 had improvement of platelet counts. Responses occurred slowly, with continued improvements occurring up to a year after starting treatment.
TYROSINE KINASE INHIBITORS: Gleevec® is the first tyrosine kinase inhibitor approved for the treatment of cancer. Many clinical trials are currently underway evaluating Gleevec® for the treatment of many different types of cancer including myelodysplastic syndromes. Tyrosine kinases are proteins found within a cell that help modulate the growth and replication of the cell. There are many different types of tyrosine kinases that are normally present in every cell. Cancer often develops when a genetic mutation occurs and causes a tyrosine kinase to continually stimulate growth of a cell, so that cellular replication occurs in an uncontrolled manner. Tyrosine kinase inhibitors such as Gleevec® are agents that bind to overactive tyrosine kinases found in cancer cells. This binding action renders the tyrosine kinase inactive and ultimately stops replication of the cancer cell.
MONOCLONAL ANTIBODIES: The CD33 antigen is present on myeloid cells and can be used as a target for monoclonal antibodies. Some monoclonal antibodies can locate cancer cells and stimulate the immune system to kill them. However, some antibodies have to be linked to a radioactive isotope or a toxin in order to kill cells and the antibodies essentially serve as a delivery system. Monoclonal antibodies can be administered alone or with chemotherapy and are being evaluated to determine whether they can improve cure rates.
DIFFERENTIATING AGENTS: The process of differentiation is the normal transition from an immature cell (i.e. blast) to a mature or "fully differentiated" blood cell. Doctors are evaluating agents that help differentiation into normal blood cells.
UMBILICAL CORD TRASPLANT: Umbilical Cord Transplant May Be Effective Treatment Option for Some Patients with Myelodysplastic Syndromes © CancerConsultants.com; http://www.CancerConsultants.com
According to a recent article published in the journal Blood, an umbilical cord transplant may be an effective treatment option for patients with myelodysplastic syndrome that are not able to find a suitable donor for an allogeneic stem cell transplant. Myelodysplastic syndrome (MDS) is a disease in which the cells in a person’s bone marrow are not functioning normally. The bone marrow (and circulating blood) contains early blood-forming cells called stem cells, which grow and mature into the 3 blood cell types: white blood cells, which protect the body from infection; red blood cells, which carry oxygen to the tissues; and platelets, which help the blood to clot. In the case of MDS, not enough normal blood cells are being produced and/or the blood cells die prematurely. This condition is sometimes referred to as a pre-leukemia or "smoldering" leukemia because it often develops into leukemia, a type of cancer.
Some patients with MDS also have additional abnormalities, including genetic abnormalities of the blood cells, a high number of immature blood cells (called blasts) in the bone marrow, or decreasing numbers of red blood cells, white blood cells, or platelets. These individuals are at a higher risk for a more rapid progression to leukemia than are those who have more favorable cell features. There are five different stages, or extent, of MDS that include (in order of disease progression) refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transition, and chronic myelomonocytic leukemia. An allogeneic stem cell transplantation is considered the only curative therapeutic option for MDS. Cancers are often treated with high doses of chemotherapy and/or radiation followed by a stem cell transplant. Although high-doses of therapy are more effective at killing cancer cells, many other cells in the body are also destroyed by the treatment procedure, including stem cells. Stem cells are immature blood cells produced in the bone marrow which mature into either red blood cells, white blood cells, or platelets.
A stem cell transplant is a procedure that replaces the stem cells that are destroyed by high-dose chemotherapy and/or radiation therapy with healthy stem cells. In the case of an allogeneic stem cell transplant, stem cells are collected from the blood or bone marrow of a related or unrelated donor and infused into the patient after high-dose chemotherapy or chemotherapy plus total body irradiation. In addition to the anti-cancer effect of the high-dose therapy, an allogeneic stem cell transplant induces a second anti-cancer effect called the graft-versus-leukemia effect. This effect occurs after a transplant, whereby the presence of the foreign donor stem cells (ie, the graft) attacks the remaining cancer cells. However, the donor lymphocytes may also attack the patient’s healthy tissues, causing what is called graft-versus-host disease (GVHD). GVHD can be an acute or chronic disease and occurs in the majority of patients receiving allogeneic transplants. In an effort to prevent or reduce GVHD, attempts are made to match 6 different proteins (HLA) found on stem cells between donors and patients. Many patients that could be cured with an allogeneic stem cell transplant do not have an appropriate stem cell donor. Over the past decade, researchers have learned that umbilical cord blood is a rich source of stem cells. Umbilical cord blood stem cells have been used to support high-dose chemotherapy treatment of infants and children. Now, there is a peaking interest in the use of umbilical cord blood as a source of stem cells for adult cancer patients who undergo allogeneic stem cell transplant. Recently, there has been a concerted government-funded effort to establish umbilical cord “banks” where umbilical cord blood is frozen and stored. These “banks” are now being integrated nationally and internationally with registries allowing patients to search for a stem cell donor. Thus, if a patient is unable to find a related donor, a search can be performed for an appropriate umbilical cord blood source of stem cells in various banks around the world.
The major disadvantage of using umbilical cord blood is the low number of stem cells collected. The lack of adequate numbers of stem cells in umbilical cord blood units has limited the use of this source of stem cells in adult patients, especially large adults who require more stem cells. Methods through which to expand the number of collected stem cells through laboratory processes are currently under investigation. Researchers from Japan recently conducted a clinical trial to evaluate the effectiveness of umbilical cord transplants in 12 patients with advanced MDS. These patients were eligble for an allogeneic stem cell transplant, but an appropriate donor could not be found. Two years following therapy, 76% of patients were alive and cancer-free. Acute GVHD occurred in 75% of patients and chronic GVHD occurred in approximately 73% of patients.
The Researchers concluded that umbilical stem cell sources should be offered to patients with MDS who are eligible for an allogeneic stem cell transplant but are not able to find a suitable donor. Patients with MDS who are considering an allogeneic stem cell transplant but cannot find a donor may wish to speak with their physician about the risks and benefits of an umbilical cord transplant or the participation in a clinical trial evaluating this or other therapeutic options. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients.
NEUMEGA Pilot Study Indicates Neumega® Produces Responses In Myelodysplastic Syndrome © CancerConsultants.com; http://www.CancerConsultants.com
According to an article recently published in the Journal of Clinical Oncology, preliminary research suggests that low-dose Neumega® is well-tolerated and active for certain patients with myelodysplastic syndromes.
The Food and Drug Administration has approved the blood cell growth factor Neumega® for the prevention of chemotherapy-induced thrombocytopenia (lack of platelets). Neumega® helps the bone marrow create more platelets and has been demonstrated in clinical studies to prevent thrombocytopenia and decrease the need for platelet transfusions in patients at high risk for developing thrombocytopenia. Higher dose Neumega® may not be tolerated over long periods of time due to fluid accumulation. The effects of long-term, low-dose Neumega® in cases of bone marrow failure have not been investigated until now.
Researchers at M.D. Anderson Cancer Center recently conducted a pilot study to determine the activity of Neumega® in patients with bone marrow failures. Eleven patients with MDS received at least 2 courses of low-dose Neumega®. After the first 2 courses, patients showing evidence of a response continued receiving low-dose Neumega® maintenance therapy. Platelet response was defined as a doubling of platelets for a duration of 4 weeks. Approximately 45% of patients showed platelet response to the Neumega®. The side effects from treatment were mild.
The results of this pilot study indicate that low-dose Neumega® therapy appears to be well-tolerated and may activate a platelet response for certain patients with MDS. However, this is a small, pilot study and much research is warranted to further define the role of Neumega® for the treatment of bone marrow failure.
Patients with MDS or other conditions with bone marrow failure may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating Neumega® therapy or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute ( cancer.gov
Anti-Inflammatory Drug Combination Appears to Improve Blood Counts for Persons with Myelodysplastic Syndrome © CancerConsultants.com; http://www.CancerConsultants.com
A myelodysplastic syndrome is a disease of the bone marrow that eventually progresses into leukemia, a type of cancer. While 1 curative option for myelodysplastic syndrome is a procedure called a stem cell transplantation, not all persons are able to tolerate the potentially life-threatening complications that can occur with this procedure. For these persons, biologic agents and chemotherapy drugs are used to help the bone marrow produce more normal blood cells, relieve the signs and symptoms of disease, and prolong survival time. Now, researchers say that a combination of pentoxifylline, ciprofloxacin, amifostine, and dexamethasone appears to be an effective new treatment option for improving blood cell counts.
Other than stem cell transplantation, treatment of myelodysplastic syndrome often consists of the infusion of red blood cells or platelets to compensate for the inadequate production of these cells in the bone marrow. Biologic agents, such as Neupogen and erythropoietin, are also used to help white and red blood cells to grow more rapidly. One new treatment approach is the use of inflammatory cytokine suppressants, which inhibit the production of inflammatory cytokines. Researchers used 2 such drugs, pentoxifylline and dexamethasone, to treat persons with myelodysplastic syndrome. They also combined these agents with 2 helper drugs, ciprofloxacin to enhance the level of pentoxifylline in the blood and Ethyol® to protect healthy cells and further enhance blood cell counts.
Researchers at the Rush Cancer Institute treated 35 persons with myelodysplastic syndrome. The types of myelodysplastic syndrome treated included refractory anemia, refractory anemia with sideroblasts, refractory anemia with excess blasts, chronic myelomonocytic leukemia, and myelodysplasia from previous drug treatment. Each person received pentoxifylline, ciprofloxacin, and amifostine; patients who did not respond or who responded only partially to this therapy also received dexamethasone. The results showed that 22 persons responded to this treatment strategy with an improvement in white blood cell, red blood cell, and/or platelet counts. Nineteen had an improvement in white blood cell count, 11 had an improvement in hemoglobin (an iron-rich protein on red blood cells) levels and/or a 50% reduction in the number of blood transfusions required; and 7 had an improvement in platelet count. These responses occurred slowly, with improvements continuing up to 1 year after the treatment began. There were no significant side effects, except for nausea and vomiting.
These findings suggest that pentoxifylline, ciprofloxacin, and amifostine, either with or without dexamethasone, is an effective and safe combination for achieving improved blood cell counts in persons with myelodysplastic syndrome. Persons who have myelodysplastic syndrome may wish to talk with their doctor about the risks and benefits of the pentoxifylline/ciprofloxacin/amifostine/dexamethasone regimen, or of participating in a clinical trial in which other new treatments are being studied. Sources of information on ongoing clinical trials that can be discussed with a doctor include a comprehensive, easy-to-use service provided by the National Cancer Institute ( cancer.gov
NOTE: It is important to note that patients with myelodysplastic syndrome may wish to collect stem cells early in the course of their treatment, as this may not be an option later.