Acquired bone marrow aplasia

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Dr. Lucrecia Yáñez San Segundo. Hematology Service, Hospital Universitario Marqués de Valdecilla. Associate professor, Dpt. Medicine and Psychiatry, University of Cantabria

What is acquired bone marrow aplasia and why does it occur?

Bone marrow aplasia is a disease in which the red bone marrow disappears and consequently ceases to produce red blood cells, white blood cells and platelets.

Bone marrow aplasias can be distinguished between congenital, the most frequent, and acquired aplasias. Bone marrow aplasia caused by a congenital alteration (Fanconi anemia, dyskeratosis congenita) is less frequent than acquired bone marrow aplasia and is caused by a genetic change that can affect other organs. Patients therefore frequently present other alterations which may be visible from birth.

Acquired bone marrow aplasia is caused by the disappearance of the hematopoietic stem cells, either secondary to direct damage produced by a toxin, or through an immunological mechanism whereby the patient's lymphocytes themselves recognise the stem cells as foreign, and destroy them. Although it is sometimes possible to relate acquired bone marrow aplasia with a causative factor such as the ingestion of a drug, contact with chemical agents, pesticides, benzine, paints and ionising radiation, or having suffered from certain viral infections (hepatitis being the most frequent), in most cases (80%) it is not possible to identify the cause.

Who is affected by acquired bone marrow aplasia?

Bone marrow aplasia is considered to be a rare or infrequent disease, that is to say, the percentage of the population diagnosed and suffering from it is very low (< 0.05%). In Europe and north America the estimated incidence is between 1.5 and 2 new cases per million, per year. However this incidence may be up to three times greater in certain geographical areas such as the Far East, southwest Asia (Japan and China) and Mexico.

Acquired bone marrow aplasia generally affects teenagers and young adults (15-25 years of age) and people over the age of 60. It affects both sexes equally.

What are the symptoms for bone marrow aplasia?

The bone marrow works like a factory. It produces red blood corpuscles (or red blood cells, responsible for transporting oxygen to the tissues), leucocytes (or white blood cells, responsible for defending the body against infection), and platelets (responsible for avoiding hemorrhages).

With bone marrow aplasia, as a consequence of the failure to produce these elements of the blood, patients may present various symptoms, and to different degrees, depending on the deficit. A deficit of red blood cells (anemia) can manifest itself as tiredness, weakness, paleness, dizziness, palpitations and headache, although, in general, the anemia is usually well tolerated because it establishes itself slowly and progressively. A deficit of white blood cells (leukopenia and neutropenia) can lead to mouth ulcers and continuous infections. A deficit of platelets (thrombopenia) can lead to bruising after the slightest knock, bleeding of the gums, nose or conjunctiva, as well as more serious bleeding from any other parts of the body.

How is a patient with bone marrow aplasia diagnosed?

A blood test (hemogram) to study some of the symptoms mentioned previously, can lead to a suspicion of bone marrow aplasia. Usually the blood count shows low numbers of red blood cells, white blood cells and platelets (pancytopenia), however, diagnosis can not be confirmed until there has been a study of the bone marrow architecture by means of a biopsy. A bone marrow biopsy is a straight forward procedure in which, by means of puncturing the hip, a small cylinder of bone is obtained. At the same time the biopsy is performed a blood sample is also taken from within the bone marrow (aspiration) and this is used to complement the biopsy studies in order to differentiate between acquired bone marrow aplasia and other causes of pancytopenia.

It is possible to talk about less severe, severe and very severe bone marrow aplasia, depending on how intensely the bone marrow is affected.

What is the treatment for acquired bone marrow aplasia?

As with other hematological diseases treatment for acquired bone marrow aplasia combines directed treatment and support treatment.

Support treatment: The aim of support treatment is to alleviate the patient's symptoms. In order to improve the manifestations deriving from the anemia, patients are administered a red blood cell transfusion. If there is secondary bleeding due to the lack of platelets, a platelet transfusion is administered. In cases where there is fever, a course of antibiotics is administered and, given that such patients have low defences, the necessary levels of hygiene must be observed to avoid further infections.

Patients with less severe aplasia may almost be asymptomatic and not require such support treatment.

Directed treatment: In cases where the cause of the bone marrow aplasia has been established, the main treatment is to suppress the causal agent. Sometimes androgens (male hormones) are used to correct the aplasia, however, it must be borne in mind that these drugs might have significant side effects and are more effective in those aplasias associated with protein defects that keep the size of the chromosomes stable (telomerase). 

As mentioned at the beginning, acquired bone marrow aplasia presents secondary to an autoimmune mechanism and patients are treated with immunosuppressive drugs in association, on occasion, with a stem cell transplant.

Patients with less severe aplasia must be treated with an immunosuppressive agent called cyclosporin A in association, sometimes, with anti-thymocyte globulin (better known as ATG) and factors to stimulate hematopoiesis (such as G-CSF). Symptoms are resolved with this treatment for 50-60% of patients although, in a third of cases the aplasia may reappear after time, it being necessary to repeat the treatment.

The treatment of choice, for severe and very severe bone marrow aplasias for patients under the age of 40, is a bone marrow transplant from a sibling or histocompatible (HLA identical) non-related donor. With this procedure up to 90% of patients find a cure.

For older patients, or those who do not have an HLA compatible donor, treatment is based on the administration of anti-thymocyte globulin (ATG) in association with a cyclosporin A. These drugs resolve the aplasia in 50-70% of cases, although a third of patients will suffer a relapse some time afterwards and the responses achieved are mostly partial (the blood count does not return to normal). Although it is still pending authorisation by some health authorities, a recent study has observed that the addition of a drug to stimulate hematopoiesis (eltrombopag) at the beginning of treatment with ATG and cyclosporin A increases the number of global and complete responses. The worst responses are those of patients over 40 years of age with very severe aplasia. 

In cases of relapse, or if the patient does not respond to initial treatment, a second course of immunosuppressive treatment (30% response) should be considered, as should the administration of eltrombopag (45-50% response), or a bone marrow transplant if there is a haploidentical or compatible donor (related or non-related).

What is the prognosis for acquired bone marrow aplasia?

The long-term prognosis depends on the severity of the aplasia, the patient's age, earliness in starting the immunosuppressive treatment and the availability, or otherwise, of a compatible (related or non-related) donor. Two thirds of patients who receive immunosuppressive treatment are cured after one or two courses. With a bone marrow transplant the probability of a cure varies between 70-95% for transplants from compatible siblings, and 70-85% for transplants from non-related donors.

Links of interest concerning medical issues relating to bone marrow aplasia

For more quality information about bone marrow aplasia you can consult the following websites:

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Webpage updated 01/09/2023 13:02:29