Basic Aplastic Anemia Therapeutic Algorithm

The figure shows the currently established therapeutic algorithm of acquired adult AA. The general consensus of whether to do a transplant or immunosuppression (IS) is structured according to the age of patients; with increasing age IS may provide more favorable survival results than BMT. However, even very intense IS may not be sufficient to eradicate the autoimmune process, and prolonged maintenance therapy may be needed for the prevention of relapses.



Reference:
Aplastic Anemia: Management of Adult Patients
Jaroslaw P. Maciejewski and Antonio M. Risitano
Hematology 2005 (1): 110

Data on Erythropoietin (EPO) plus G-CSF

Since a multilineage response in patients treated with G-CSF or EPO alone is uncommon, several investigators have combined EPO and G-CSF. In most of the patients, responses were restricted to neutrophils and erythrocytes with trilineage responses occurring in a minority of patients. One of these studies compared different doses of EPO [0, 200, 400U/kg three times a week (t.i.w.), and reported that the highest erythroid response rate (37%) was in the group of patients who received 400 U/kg t.i.w.

Combinations of G-CSF and EPO with immunosuppression produced encouraging results. However, since all these trials were performed without a control group it is not possible to estimate the importance of the various components of the multimodal treatment.

The spreadsheet below contains data on published reports of patients with aplastic anemia with erythropoietin and G-CSF.

What is a "Control Group"?

When studying the medical literature on any disease, we will often find that the authors will state whether a "Control Group" was used in their study/clinical trial.

A clinical control group is a group of individuals, involved in a medical experiment, who do not receive the treatment, in order to determine the effectiveness of the drug, supplement or treatment being tested.

Comparing the results of a group receiving treatment with the clinical control group is essential to help rule out imagined or random effects of the treatment. In the United States, the Food and Drug Administration (FDA) provides some guidelines about how the groups should be selected; in general the control group and the group receiving the treatment should be as identical as possible.

If a drug is being tested, the control group will frequently be given a placebo. This is done as a double blind test, as neither the doctor nor the patient know if they are receiving the drug under test or a placebo, and don't find out which substance was administered until after the experiment is concluded.

What about using Procrit / Epogen?

Procrit or Epogen are brand names for epoetin alfa (ih-POH-ee-tin), a man-made version of human erythropoietin (EPO).

Epogen or Procrit promotes red blood cell production in the bone marrow and is known as a growth factor. Growth factors are normal chemicals in the body that encourage the bone marrow to make blood cells. Growth factors have been manufactured as drugs to stimulate the bone marrow to produce more blood cells.

EPO is produced naturally in the body, mostly by the kidneys. It is approved by the U.S. Food and Drug Administration (FDA) for use in patients with kidney disease. EPO has been helpful for treating anemia in some patient with MDS, although there is still a need to define more exactly which subset of patients are most likely to benefit. EPO may be helpful, but much more rarely also in patients with aplastic anemia or PNH.

Click on the image below to see some published data on the outcome of using EPO on patients with AA.

Mia Hamm signs deal with umbilical cord blood bank

Former soccer star Mia Hamm announced a partnership with Cambridge-based umbilical cord blood bank ViaCord yesterday.

Umbilical cord blood is a source of stem cells, which can be frozen and stored to treat diseases later in life.

Hamm’s brother, Garrett, died of aplastic anemia, which could have been treated had cord blood been available. After researching the procedure, Hamm and husband Nomar Garciaparra chose last year to save the cord blood of their twin girls, Ava and Grace, with ViaCord.

“Obviously it was a very personal decision,” says Dan Levy, Hamm’s agent. “Not that everyone has to do it, but she felt the need to educate people that the option is out there.”

According to Viacord’s Web site, the company charges $1,920 for the initial collection and processing of the cord blood, plus $150 for transporting the blood by courier, plus a yearly storage fee of $125, a total of $2,195 for opening an account. They also offer 6-, 12- and 60-month payment plans.

Currently, the company is advertising $100 off that price and will donate $25 to the Mia Hamm Foundation.

Source: "The Boston Herald"

Blood Cell Production

Blood is a “circulating tissue” of the body. It is composed of many specialized cells suspended in plasma. Two of its main functions are to transport oxygen and nutritive materials (food) to the tissues of the body and to transfer waste products to disposal sites. Blood also transports the body’s defense cells to areas damaged through injury or infection.
There are three major types of blood cells: Red Blood Cells (RBCs) or erythrocytes; White Blood Cells (WBCs) or leukocytes; and Platelets.

Production

All blood cells arise from a common origin in the bone marrow, the hematopoietic stem cells (HSCs). These stem cells can differentiate into one of three major cell lines: the leukocytes, the platelets, and the erythrocytes. The exact details of how the numbers of circulating cells of each type are regulated remain somewhat obscure, though the broad outlines are clear.

The rate of blood cell production is controlled by the body’s needs. Normal blood cells last for a limited time (ranging from a few hours to a few days for white blood cells, to about 10 days for platelets, to about 120 days for red blood cells) and must be replaced constantly. Certain conditions may trigger additional production of blood cells. When the oxygen content of body tissues is low or the number of red blood cells decreases, the kidneys produce and release erythropoietin (Some Trade Names EPOGEN PROCRIT), a hormone that stimulates the bone marrow to produce more red blood cells. The bone marrow produces and releases more white blood cells in response to infections. It produces and releases more platelets in response to bleeding.

The bone marrow in a healthy adult produces about 2.5 billion red blood cells (RBCs), 1 billion white blood cells (WBCs), and 2 billion platelets for every kilogram (2.2 lbs) of body weight every day.


References:
The Merck Manual

A Mathematical Model of Hematopoiesis – I. Periodic chronic myelogenous leukemia
Journal of Theoretical Biology 237 (2005); 117–132

Incidence of Aplastic Anemia

Aplastic Anemia can strike anyone of any age, race, or gender. The incidence of AA shows geographical variability. In Europe and the U.S. the rate is about 2 cases per million people per year (approximately 500 total cases in the U.S. every year). However, the studies carried out in Asia show a 2-to 3-fold higher rate.

Nobody really knows why these differences exist. Much of the literature cite the possible differences in exposure to environmental factors including viruses or drugs and chemicals. Other possibilities could be genetic background, diagnostic criteria, or study designs.

References:
Epidemiology of aplastic anemia: a prospective multicenter study
Haematologica (2008); 93(4):518-523

Regional Patterns in the Incidence of Aplastic Anemia in Thailand
American Journal of Hematology (1999); 61:164-168