Aplastic Anemia Aplastic Anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… is a rare bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… disease that can affect both young and adult patients. Patients with this disease have an empty bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. and have low blood counts. The low blood count puts the patients at risk for infections and frequently necessitates the need for transfusions with blood products. The disease can develop from unknown causes (idiopathic) or can be due to drugs, toxins, chemotherapy chemotherapy: (kee-moe-THER-uh-pee) The use of medicines that kill cells (cytotoxic agents). People with high-risk or intermediate-2 risk myelodysplastic syndrome (MDS) may be given chemotherapy to kill bone marrow cells that have an abnormal size, shape, or look. Chemotherapy hurts healthy cells along with… (acquired). Idiopathic Idiopathic: Usually refers to any condition with no known cause. aplastic anemia is caused primarily by an abnormal immune system. Hematopoietic bone marrow transplant bone marrow transplant: A bone marrow transplant (BMT) is also called a stem cell transplant (SCT) or hematopoietic stem cell transplant (HSCT).The procedure replaces unhealthy blood-forming stem cells with healthy ones and offers some patients the possibility of a cure. But for many patients, a BMT is not an option due… is a potential cure for idiopathic aplastic anemia patients. However, not all aplastic anemia patients can undergo hematopoietic bone marrow transplant. Drugs that suppress the immune system are the main treatment for patients with aplastic anemia who lack suitable donors or ineligible for bone marrow transplant. Horse Antithymocyte globulin Antithymocyte globulin: ATG is an immunosuppressant, a drug that lowers the body's immune response. It is typically used with cyclosporine as the first-line immunosuppressive therapy (IS) to treat patients with acquired aplastic anemia. In some cases it is used as a treatment for patients with MDS and PNH. (ATG) is the best first treatment for newly diagnosed severe aplastic anemia patients who are not candidates for transplant. However, some patients with aplastic anemia treated with ATG do not respond (refractory aplastic anemia) and others have an initial response but lose it again (relapsed aplastic anemia). Understanding this problem in treating aplastic anemia patients, we wanted to explore alternative immunosuppressive therapies for the treatment of patients with relapsed/refractory aplastic anemia.
Alefacept is a novel immunosuppressive agent that targets the CD2-LFA3 pathway. The CD2-LFA3 pathway is important in the function of T lymphocytes, cells that play important roles in immunity and are thought to contribute to disease in aplastic anemia. This Phase I/II study was fully approved by the Institutional Review Board Institutional Review Board: A committee that makes sure a clinical trial is safe for patients in the study. Each medical center, hospital, or research facility doing clinical trials must have an active Institutional Review Board (IRB). Each IRB is made up of a diverse group of doctors, faculty, staff and students at a… of the Cleveland Clinic and conducted in patients with relapsed/refractory aplastic anemia.
A total of four patients were successfully enrolled in this trial. All four patients had refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. aplastic anemia. None of the patients had a PNH clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. at presentation. Improvements in blood counts were noted in three out of the four patients. Side effects were very mild and included cough, sore throat, and nasal congestion in one patient and mild muscle aches in a second. All side effects were temporary and disappeared after 2 weeks of treatment. No severe side effects were reported. To date, three out of four patients who achieved improvements in blood counts continue to not require blood transfusions or any other immunosuppressive therapies such as cyclosporine cyclosporine: Cyclosporine is used along with antithymocyte globulin (ATG), another immunosuppressant, for treating aplastic anemia and some other forms of bone marrow failure. . All four patients have not developed a PNH clone. In December 2011, Astellas Pharma US announced that the company has voluntarily discontinued the promotion, manufacturing, distribution and sales of alefacept because of business needs but not related to safety issues. In conclusion, targeting CD2-LFA-3 pathway using alefacept is a safe option for treating patients with relapsed/refractory aplastic anemia.
Ramon Tiu is an Assistant Professor of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and is associate staff in the Department of Translational Hematology and Oncology Research and Department of Hematologic Oncology and Blood Disorders at Cleveland Clinic. He completed his medical school training at the University of Santo Tomas Faculty of Medicine and Surgery in the Philippines and subsequently pursued internal medicine training at Cleveland Clinic from 2003-2006. He pursued further research training in experimental hematology as a bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… research fellow at Cleveland Clinic under the tutelage of Dr. Jaroslaw P. Maciejewski, which he continued throughout his fellowship training in hematology and oncology at the same institution. He is well published in the area of single nucleotide polymorphism arrays, especially in their clinical application in myeloid malignancies like myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS) and acute myeloid leukemia acute myeloid leukemia: (uh-KYOOT my-uh-LOYD loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become… (AML). He is a young investigator awardee from the MDS Foundation and the Aplastic Anemia Aplastic Anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… and MDS International Foundation and a prior recipient of a T32 research award from Case Western Reserve University. He is involved in both clinical and translational research, focusing mainly on the field of myeloproliferative neoplasms and bone marrow failure syndromes. His laboratory research team recently identified a gene called SF3B1 to be frequently mutated in cases of MDS with ring sideroblasts, specifically refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. anemia anemia: (uh-NEE-mee-uh) A condition in which there is a shortage of red blood cells in the bloodstream. This causes a low red blood cell count. Symptoms of anemia are fatigue and tiredness. with ring sideroblasts (RARS) and RARS associated with marked thrombocytosis (RARS-T). SF3B1 is a gene involved in an important physiologic post-transcriptional process called splicing. This is an unprecedented finding, as this is the first time that the spliceosome machinery has been implicated as a possible cause in blood cancers, particularly in MDS. Recently, his research team showed the first experimental evidence linking SF3B1 dysfunction and the formation of ring sideroblast ring sideroblast: (SID-uh-ruh-blast) A red blood cell that has too much iron. The iron typically forms a ring around the cell's nucleus. in MDS. He is also very active in conducting clinical trials clinical trials: Clinical research is at the heart of all medical advances, identifying new ways to prevent, detect or treat disease. If you have a bone marrow failure disease, you may want to consider taking part in a clinical trial, also called a research study. Understanding Clinical Trials Clinical… in bone marrow failure syndromes and myeloproliferative neoplasms (MPNs) and an active clinician seeing patients with MDS, MDS/MPN overlap syndromes, MPNs and rare bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. failure conditions like Aplastic Anemia, PNH and LGL leukemia. He is board certified in Internal Medicine, Hematology and Oncology.