Cancer Treatment Today » Anemia

Ferriprox for treatment of sickle cell anemia

M Levin, MD — Sun, 08 Sep 2013 20:08:21 +0000

FERRIPROX® (deferiprone) is an oral medication designed to chelate, or remove, iron overload from transfusions due to thalassemia syndromes when other chelation therapy, most commonly Exjade, does not work. The studies for approval were done for teh situation when teh initial chaltion did not work (second line) because Ferroprox may be inferior to Exjade in first line. This is not an innocuous drug; the most serious side effect seen in about two percent of patients treated with Ferriprox was low white counts, a serious and potentially life-threatening complication. This drug is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs, that had not been fully studied and thatmust followed by further studies to confirm the drug’s benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on initial data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients, or on an effect on a clinical endpoint other than survival or irreversible morbidity (illness). The assumption that these parameters can be counted on to predict ultimate effectiveness is not universally accepted.

ApoPharma has agreed to several post-marketing requirement and commitments. One commitment includes further study of the use of Ferriprox in patients with sickle cell disease who have transfusional iron overload. One such study is: Absorption, Metabolism, and Excretion of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease, NCT01835496.

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Ferriprox for sickle cell anemia

M Levin, MD — Wed, 17 Jul 2013 18:30:31 +0000

FERRIPROX® (deferiprone) is an iron chelator indicated for the treatment of patients with iron overload form transfusions due to thalassemia syndromes when current chelation therapy, most commonly Exjade, is inadequate. The approval in second line is reasonable both because the studies for approval were done in second line and because Ferroprox may be inferior to Exjade in first line (Cemak et al). This is not an innocuous drug; the most serious side effect seen in about two percent of patients treated with Ferriprox was the development of bone marrow failure to produce white cells, a serious and potentially life-threatening complications. The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients, or on an effect on a clinical endpoint other than survival or irreversible morbidity (illness).

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Cyclosporine for Aplastic Anemia

M Levin, MD — Sun, 28 Apr 2013 12:34:08 +0000

Aplastic anemia in younger patients is generally an immune disorders, in which the immune system attack newly forming red cells and kills them. For this reason, it is often treated with immunosuppression. The risks of supressing the immune system is greater in older people, and for this reason, the suppression of the immune system is more often used in younger patients. Older individuals and those who failed immune suppressing drugs, should go on to stem cell transplantation. When there is no sibling donor, cyclosporine(CSA) is recommended, usually in combination with other drugs but it can also be used alone. First-line treatment approaches include immunosuppressive treatment using the combination of antithymocyte globulin and cyclosporine A for patients without a sibling donor and HLA identical sibling transplant for patients younger than age 40 with a donor. Despite a theoretical rationale for its use, sirolimus did not improve the response rate in patients with severe aplastic anemia when compared to standard h-ATG/CsA.

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Testing for Alpha-thalassemia

M Levin, MD — Sun, 21 Apr 2013 12:31:49 +0000

The human alpha gene is found on the short arm of chromosome 16 and there are two hemoglobin alpha chain genes, HBA1 and HBA2. Almost all alpha thalassemias result from a loss of one or more of the alpha genes; the more genes dropped, the more severe is the disease. Unlike Beta-thalssemia, which is found around the Mediterranean, alpha-thalassemias is more geographically widespread and can be found in the descendents of people from Africa and Asia, as well as the Mediterranean. . Molecular genetic testing of HBA1 and HBA2 detects loss of genes in about 90% and point mutations inside a gene in about 10% of affected individuals.

Testing is indicated for:
•Patients with symptoms of alpha-thalassemia or anemia with smaller read cell size.
•Family members of an affected patient who are at risk to be carriers of alpha-thalassemia.
•Carrier screening for individuals of Asian, African, and Mediterranean background.

Individuals with beta thalassssemia trait rarely have anemia and another coexistent gemoglobin mutation should be looked for, if anemia is present. Workup consists of laboratory evaluation, especially CBC, hemoglobin electrophoresis, and genetic testing.

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Conditioning for allogeneic transplantation in Aplastic Anemia

M Levin, MD — Fri, 24 Aug 2012 19:43:35 +0000

Stem cell Transplantation is the only curative therapy long term for Aplastic Anemia(AA). Before stem cells can be transfused, the marrow needs to be conditioned. In younger patients with Aplastic Anemia, the standard conditioning proposed by the Working Party(WPSAA) on AA is cyclophosphamide 50 mg/kg 32 × 4 + ATG. This regimen does not completely destroy the patient’s bone marrow and it is highly immunosuppressive in order prevent graft rejection and GVHD. Often ATG(Thymogen/ anti-thymocyte globulin)) for more immunosupression is also added. The benefit of adding ATG to cyclophosphamide is unclear, because a recently published prospective randomized clinical trial (RCT) from CIBMTR showed no significant benefit in terms of graft rejection, GVHD, and survival rates, compared with cyclophosphamide alone. Raw unadjusted data, from the EBMT database, however, show a slightly superior 10-year survival of 85% versus 75% when ATG is used as part of the conditioning regimen in sibling donor transplantation.

Patients older then 30 years of age, do less well with allogeneic transplantation because they tolerate GVHD less well. There is some support for using fludarabine, a more immunosupressive drug, for such patients. Fludarabine based conditioning regimen may reduce the negative impact of age in older patients receiving an HLA-identical sibling stem cell transplant Alemtuzumab is a new drug that has been studied and that may also decrease the risk of Graft versus Host Disease. A recent European retrospective review of the combination of Fludarabine, cyclophosphamide and antithymocyte globulin(FCA), with or without low dose total body irradiation, concluded that TBI might have a role. The overall survival was quite comparable for the two regimens, though significant differences were found following more detailed analysis of subgroups. FCA conditioning regimen seems suitable for very young patients with well-matched donors; in other settings the addition of TBI 2 Gy to the FCA regimen seems to offer a better chance of cure, in keeping with results of other recent studies

There is no comparative information for any specific conditioning regimen in young adults with Aplastic Anemia. FCA is as well supported as other alternatives. For that reason, since stem cell transplantation is well established for Aplastic Anemia and the conditioning regimens are a part of this established procedure, the FCA regimen should not be considered Experimental or Investigational and it is medically necessary. The evidence for TBI is weak for young patients and TBI is experimental and it is not medically necessary.

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Nutritional Deficiencies in Scleroderma and Related Disorders

M Levin, MD — Sun, 05 Aug 2012 13:57:43 +0000

Nutritional deficiencies in scleroderma and related disorders often include folate and Vit. B12, and more recently reported, Vit. D and E, due to bacterial overgrowth in the gut. Metanx is sometimes prescribed for these conditions. Metanx is a food which is formulated to be consumed or administered by mouth under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation. Specifically it is formulated for diabetic neuropathy. The usual adult dosage of Metanx® is one tablet twice daily .Each Metanx® tablet contains: L-methylfolate Calcium (as Metafolin®) 3mg, Pyridoxal 5′-phosphate 35mg, Methylcobalamin.

Metanx is a “legend vitamin”. Legend vitamins are specific formulations that are intended to reverse nutritional deficiencies in various conditions. Metanx® tablets are indicated for the distinct nutritional requirements of patients with who present with loss of protective sensation and neuropathic pain in their arms and legs associated with diabetic peripheral neuropathy. Metanx® tablets are also indicated for the distinct nutritional requirements of patients with endothelial dysfunction and/or hyperhomocysteinemia who present with lower extremity ulceration(s). Rigorous research on “legend vitamins” is lacking but there is usually little downside to using them with the consent of your healthcare provider.

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Transfusing Young Anemic Women: A Careful Assessment is Required

M Levin, MD — Wed, 20 Jun 2012 17:53:14 +0000

Anemia is common in young women and is usually due to iron deficiency. If anemia has a slower, subacute onset, younger patients without significant medical problems can tolerate low hemoglobin levels. Often times, however, in addition to being anemic for some time, young women may have recently bled. In this situation there is less time for the body to become used to the low red cell levels and a moderate anemia may cause symptoms, such as, shortness of breath, rapid heart beating, difficulty in exerting oneself, or profound tiredness. This is means that a careful and complete clinical assessment is required before a blood transfusion is offered and that transfusions should not be given for based on low hemoglobin levels alone. Blood transfusions come with some risks. Transfusions can rarely cause allergic reactions and transmit infections and several studies have shown that patients who receive transfusions, on average, stay in the hospital longer, have higher hospital bills, and are generally more ill than patients who did not receive a transfusion. Some studies have even shown a greater likelihood of death in extensively transfused patients. Since each unit infuses over at least four hours, and time is needed for observation between and after the two units often an admission for transfusions can be appropriate, or they can be given on the outpatient basis or in the emergency room.

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