U.S. Held In Highest Regard For Cure

If there will be a cure found for Aplastic Anemia, and we believe that there will one day be a cure, that cure will come from the United States. Senator McCain, you have the power to kill thousands.

Dear Senator McCain I am not a U.S resident but have the utmost respect for you country as you have always been great allies to England I am asking you to please not take away the funding into bone marrow disease research I dont have to rem...ind you of these terribble diseases as I know you are aware and I know resources are difficult but you are a leading country and others look upto you so your research in the U.S is paramount to continue if a cure is to be found I beg you not to take this funding away forget about statisitics its real people many many children are dying I have this disease myself and to be honest it grieves me more for the children it affects they are the ones with the disease and the ones which we as adults leave behind when we die from this disease as we will without the funding. I thankyou for taking the time to read my request respectfully yours Julie Anne Theobald.

The Aplastic Anaemia–Paroxysmal Nocturnal Haemoglobinuria Syndrome

http://bloodjournal.hematologylibrary.org/cgi/reprint/48/1/63 (2007 article – the key to successful treatment according to the study is early transplant (within 17-100 days or original diagnosis)). Further reading evidences that siblings were matched for all participants in the study. Patients were given prednisone (10 mg sq m/day) to detect underlying leukemia. Cyclophosphamide was used alone for conditioning for engraftment. ATG or ATS and procarbazine (PCB) were given. After transplant, methotrexate was given to ameliorate potential graft-versus-host disease.

Summary
Study included 17 females transplanted who had idiopathic etiology (severe aplastic anemia from an unknown cause). Diagnosis was made within 17 weeks. Initial, PMN range was 0-1500 (avg 200), 1-23 platelets (avg. 6k), .1-1.4 retriculocytes (avg. .1%), and 40-99 nonmyeloid marrow cells (avg. 85%).

26 patients received CY alone, 10 CY plus ATG and PCB in preparation for engraftment.

Immunosuppression began within 12-97 days after diagnosis (avg. 33 days). Delays in treatments were due to INCOMPATIBLE DONORS, WAITING FOR AN AVAILABLE BED, DIAGNOSIS, INFORMED CONSENT (OF PATIENT AND FAMILY).

36 patients were to be transplanted; 2 died of sepsis during pretransplant immunosuppression; 34 patients were transplanted; 67% (24) survived with complete marrow restoration after 4-20 months (median 9 months). Of the 24, 2 are severely limited by GVHD; all others returned to regular activities within 3-12 months after transplantation.

No correlation was made to age, sex, etiology of aplasia, transplant cnter or transplant regimen.

Of the 34 engrafted, 10 died: 4 from infection, 2 from sepsis GVHD, 1 pneumonia and sepsis, 1 tuberculosis; 9 rejected graft (1 died before second transplant, 7 were retransplanted and of those 5 died for transplant failure and 2 were successfully engrafted).

Of the 24 that were successfully transplanted, 12 died. Of those, 8 rejected their grants within 4-5 weeks of transplant, 1 lost marrow activity during adenine arabinoside therapy begun 23 days post-transplant for disseminated herpes zoster, and 1 died before a second transplant could be attempted. 7 patients who rejected their initial grafts were re-transplanted; 2 were success.

31 patients were not transplanted. 7 improved (1 completely, 5 partially, 1 partially temporarily). Responses were seen within 1 to 3 months post treatment. Responses were positive in all three cell lines, but compared to transplant patients the responses were lesser. 19 patients died within 1-11 months due to 10 hemorrahaging, 7 from sepsis, and 2 from a combination of hemorrhage and sepsis.

Within 4 months, 67% of transplanted patients survived while only 36% of non-transplanted patients did so. Within 12 months, 75% of transplanted patients survived while only 22% of non-transplanted patients did so. At month 20, 75% of transplanted patients were still surviving while 1 non-transplanted patient survived, but has relapsed after 4 months and remains aplastic.

Notably, they say that the quick transplant choice of the patient played a key role in survival, and patients who were immediately transplanted without a prior non-transplant treatment failure clearly had much higher survival rates.

Study did not evaluate the role of intensive support in the management of severe aplastic anemia that is required during pretransplant treatment and during the 2-3 week period of the transplanted marrow beginning to function after transplant.

Some transplanted patients remained in protective environments and received oral non-absorbable antibiotics.

In the Seattle study of 23 aplastic anemia patients who survived more than 1 year after allogeneic mrrow transplantation, only one patient died, one has chronic GVHD, and one has almost completely recovered from chronic GVHD. The OTHER 20 PATIENTS ARE IN GOOD HEALTH WITH NORMAL MARROW FUNCTION AFTER 2 TO 4.5 YEARS POST TRANSPLANT.

STUDY SHOWS THAT PROMPT BONE MARROW TRANSPLANTATION SIGNIFICANTLY DECREASES EARLY MORTALITY OF SEVERE APLASTIC ANEMIA.


Cardeza Foundation, Philadelphia
Children’s Hospital, Boston
Children’s Hospital, Los Angeles
Children’s Hospital, Milwaukee
Children’s Hospital, Philadelphia
Children’s Hospital, St. Louis
Emory University, Atlanta
Hammersmith Hospital, London
Hematology-Oncology Associates PA.,
Plainfield
Hematology-Oncology Associates,
Providence
James Whitcomb Riley Hospital,
Indianapolis
J. HilIis Miller Health Center,
Gainesville
Johns Hopkins Oncology Center,
Baltimore
Milwaukee County General Hospital
Mount Sinai Hospital, New York City
Naval Medical Center, Bethesda
New Jersey Medical School, Newark
Peter Bent Brigham Hospital, Boston
Rhode Island Hospital, Providence
San Francisco Medical Center
St. Jude Children’s Research Hospital,
Memphis
UCLA
University of Capetown
University of Minnesota, Minneapolis
University of Kentucky, Lexington
University of Washington, Seattle
Yale University, New Haven
West Side V.A. Hospital, Chicago
A. Erslev
B. Camitta, D. Nathan,
R. Parkman
S. Siegel
J. Casper
S. Friedman, E. Schwartz
R. Ducos, A. Ragab,
H. Zarkowsky
T. Heffner, J. Keller
E.C. Gordon-Smith
D. Fnimmer
R. Damico
R. Baehner, A. Provisor
T. Dellinger
G. Santos
A. Pisciotta
R. Taub, R. Zalusky
R. Cahill, R. Hartzman,
K. Sell
T. Walters
J. Rappeport
E. Forman
J. Klock, S. Shohet
R. Strauss
S. Feig, R. Gale
D. Dubovsky, P. Jacobs
J. Kersey, W. Knivit
M. Greenwood, P. Holland
ED. Thomas, R. Storb
S. McIntosh, R. O’Brien
R. Epstein, W. Fried
USPHS FR-00l28
USPHS AM-05581
Tommy Fund
USPHS 5-M0l-RR-00888
USPHS CA-l7995
ALSAC
USPHS CA-12800-
RR00865
Minnesota Medical
Foundation
SMF-155-75
USPHS CA-10895

Aplastic Anemia

Aplastic anemia is a disorder in which the bone marrow greatly decreases or stops production of blood cells.

Description
The bone marrow (soft tissue which is located within the hard outer shell of the bones) is responsible for the production of all the types of blood cells. The mature forms of these cells include red blood cells, which carry oxygen throughout the body; white blood cells, which fight infection; and platelets, which are involved in clotting.

In aplastic anemia, the basic structure of the marrow becomes abnormal, and those cells responsible for generating blood cells (hematopoietic cells) are greatly decreased in number or absent. These hematopoietic cells are replaced by large quantities of fat.

Yearly, aplastic anemia strikes about 20,000-30,000 people, or 5-10 people in every one million. Although aplastic anemia strikes both males and females of all ages, there are two age groups that have an increased risk. Both young adults (between 15-30 years of age) and the elderly (over the age of 60) have higher rates of aplastic anemia than the general population. While the disorder occurs worldwide, young adults in Asia have a higher disease rate than do populations in North America and Europe.

Causes and symptoms
Aplastic anemia falls into three basic categories, based on the origin of its cause: idiopathic, acquired, and hereditary. In about (50% to) 60% of cases, aplastic anemia is considered to be idiopathic, meaning that the cause of the disorder is unknown.

Acquired Aplastic Anemia
Acquired aplastic anemia refers to those cases where certain environmental factors and physical conditions seem to be associated with development of the disease. Acquired aplastic anemia can be associated with:

• exposure to drugs, especially anti-cancer agents, antibiotics, anti-inflammatory agents, seizure medications, and antithyroid drugs (drugs given to stop the functioning of an overactive thyroid)
• exposure to radiation
• chemical exposure (especially to the organic solvent benzene and certain insecticides)
• infection with certain viruses (especially those causing viral hepatitis, as well as Epstein-Barr virus, parvovirus, and HIV, the virus which can cause AIDS)
• pregnancy
• certain other disorders, including a disease called paroxysmal nocturnal hemoglobinuria, an autoimmune reaction called graft-vs-host disease (which occurs when the body's immune system attacks and destroys the body's own cells), and certain connective tissue diseases

Hereditary Aplastic Anemia
Hereditary aplastic anemia is relatively rare, but does occur in Fanconi's anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita.

Symptoms
Symptoms of aplastic anemia tend to be those of other anemias, including fatigue, weakness, tiny reddish-purple marks (petechiae) on the skin (evidence of pinpoint hemorrhages into the skin), evidence of abnormal bruising, and bleeding from the gums, nose, intestine, or vagina. The patient is likely to appear pale. If the anemia progresses, decreased oxygen circulating in the blood may lead to an increase in heart rate and the sudden appearance of a new heart murmur.

Prognosis
Aplastic anemia is a life-threatening illness. Without treatment, it will almost surely progress to death. Survival depends on how severe the disease is at diagnosis, which type of treatment a patient is eligible for, and what kind of response their body has to that treatment. The worst-prognosis type of aplastic anemia is one associated with very low numbers of a particular type of white blood cell. These patients have a high chance of dying from overwhelming bacterial infections. In fact, 80% of all patients treated with blood transfusions alone die within 18 months to two years. Patients who undergo bone marrow transplantation have a 60-90% chance of being cured of the disease.

BOOKS:
Castro-Malaspina, Hugo, and Richard J. O'Reilly. "Aplastic Anemia and Myelodysplastic Syndromes." In Harrison's Principles of Internal Medicine, ed. Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.

PERIODICALS:
Doney, Kristine, et al. "Primary Treatment of Acquired Aplastic Anemia: Outcomes with Bone Marrow Transplantation and Immunosuppressive Therapy." Annals of Internal Medicine 126 (15 Jan. 1997): 107+.

Young, Neal. "Aplastic Anaemia." The Lancet 346 (22 July 1995): 228+.

Young, Neal, and Jaroslaw Maciejewski. "The Pathophysiology of Acquired Aplastic Anemia." The New England Journal of Medicine 336 (8 May 1997): 1365+.

ORGANIZATIONS:

Aplastic Anemia Foundation of America. P.O. Box 613, Annapolis, MD 21404. (800) 747-2820. http://www.aplastic.org/.

GLOSSARY:
Bone marrow—A substance found in the cavities of bones, especially the long bones and the sternum (breast bone). The bone marrow contains those cells which are responsible for the production of the blood cells (red blood cells, white blood cells, and platelets).

Bone marrow transplant—A procedure in which a quantity of bone marrow is extracted through a needle from a donor, and then passed into a patient to replace the patient's diseased or absent bone marrow.

Hematopoietic cells—Those cells which are lodged within the bone marrow, and which are responsible for producing the cells which circulate in the blood (red blood cells, white blood cells, and platelets).

Biologics: New Miracle Drugs

Biologics are considered the new miracle drugs. Radical recoveries are giving biologics a much-hyped reputation as miracle drugs. Biologic medicines are now the fastest-growing class of drugs in the pharmaceutical world; Avastin alone garnered nearly $3 billion in sales in 2008. Many patients today survive cancers once considered a death sentence, and those who suffer from autoimmune diseases such as multiple sclerosis or rheumatoid arthritis can regain full use of limbs once racked by crippling pain and immobility.

What makes biologic medicines unique is this: unlike conventional chemical drugs, biologics are produced by being grown inside living organisms, and specifically target human proteins that are involved in disease.


One class of biologics—known as monoclonal antibody biologics—are similar to the antibodies that the human immune system uses to fight off bacteria and viruses, only these antibodies are genetically engineered to target specific cancers.

Avastin is now also widely used to treat lung, breast, colon, and rectal cancers. Other monoclonal antibody biologics are designed to attack certain proteins (or protein receptors) on the surface of cancer cells and stop their growth. Examples of such protein inhibitors include Rituxan, which is used to treat lymphomas, and Herceptin.

Other biologics alter the function of the immune system by either suppressing or enhancing certain responses. In autoimmune diseases such as rheumatoid arthritis and psoriasis, for example, the immune system overproduces a protein that triggers a buildup of white blood cells, which leads to excessive inflammation and joint damage. Enbrel, Humira, Remicade, and other biologics in this class target that protein, called the tumor necrosis factor, and block its action. Tysabri, a biologic used to treat multiple sclerosis and Crohn's disease, blocks the passage of inflammatory cells into the brain and the spinal cord—and, in the case of Crohn's disease, into the intestines.

"These biologic agents provide a degree of selectivity not achievable with conventional chemotherapy drugs," explains oncologist Oliver Press, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle. "Many of [the biologics] can produce dramatic antitumor effects without the toxicity that historically has been associated with chemotherapy and radiation."

Biologic treatments date back to 1982, when recombinant insulin was first approved in the United States for the treatment of diabetes. (A hormone originally derived from the pancreas of animals, insulin is today made synthetically from genetically engineered human bacteria.) Since then, more than 300 biologic drugs, most of them developed in the past five years, have flooded the pharmaceutical market. Today they constitute roughly 25 percent of all new drugs approved by the FDA; by 2014, industry insiders predict, more than half of the top 100 drugs will be biologics.

Biologic treatments are very expensive. A push is on to develop generic drugs.
http://www.aarp.org/health/conditions/biologics/

AARP: Biologic Drugs