Cancer Treatment

Autoimmune hemolytic anemia basics

Lay Summary: I discuss some very basic facts about AIHA.

Autoimmune hemolytic anemia (AIHA) due to the presence of warm agglutinins is almost always due to IgG antibodies that react with protein antigens on the red blood cell (RBC) surface at body temperature. For this reason, they are called "warm agglutinins" even though they seldom directly agglutinate the RBCs. IV Gammaglobulin blocks this process.

I some cases, AIHA can be characterised by a chronic course and an unsatisfactory control of haemolysis, thus requiring prolonged immunosuppressive therapy. Sometimes when medical measures fail, it may be necessary to surgically remove the spleen (splenectomy). The clinical course of the disease may show either resistance to steroids or dependence on high-dose steroids with subsequent development of severe side effects on growth, bone mineralisation, and the endocrine system. Splenectomy is effective in about 50 to 60 percent of the time in IgG antibody diseases but is not usually effective in IgM antibody haemolysis. Splenectomy is of benefit in these people because the spleen behaves like a sieve and if it is removed, even though the RBCs are coated by antibodies, they are no longer caught and destroyed in the spleen.

IVIG is an accepted treatment for autoimmune hemolytic anemia. Unlike steroids, it does not induce remissions but is a temporizing measure until a definitve treatment can be planned and delivered.  IVIG is not as effective in AIHA as it is in ITP. Other treatments can sometimes be used.

Ucar K. Clinical presentation and management of hemolytic anemias. Oncology [Huntingt] 2002;16(9 suppl 10):163-70.

Schwartz RS, Berkman EM, Silberstein LE. Autoimmune hemolytic anemias. In: Hoffman R, Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, et al., eds. Hematology: basic principles and practice. 3d ed. Philadelphia: Churchill Livingstone, 2000:624.

Diagnosis

Diagnosis.

Diagnosis is when things get serious.

One can avoid engaging with the illness only up until the point of diagnosis. Few people forget the moment in which they learn of having a cancer diagnosis. No matter how serious and disabling the symptoms, they can be denied or rationalized away – not so the diagnosis of cancer. Denial after this point is not uncommon but it is clearly recognized for what it is – a maladoptive response to intolerable stress.

These three words overturned my life – Soraya.

However, diagnosis is a beginning. It can be a beginning of a struggle for life, of meeting challenges with courage and determination, or it can begin a process of retreat before the harsh reality of a serious illness.

Diagnosis is inextricably related to prognosis and the prognosis is what will determine the plan of treatment.  For your doctor a diagnosis of cancer launches a process of staging, and treatment planning. For the patient, it begins the process of  taking  responsibility of working with or along your health care provider.

The first question that the diagnosis often provokes is, “Doctor, are you sure?”. A better question to ask is: “How certain is the diagnosis”. As we will soon see, only a pathologic diagnosis deserves respect.

How is the pathologic diagnosis made?

One of the first things that I learned in my medical training was that there is no diagnosis of cancer without pathology. In fact, when a physician wish to ascertain that a final (rather then a clinical or preliminary) diagnosis has been obtained, he or she would ask: “Is there a pathologic diagnosis?” Without a pathologic diagnosis, not only is there no seciue diagnosis, there also cannot be treatment plan (we will discuss the rare exceptions to this principle later). Let us explain what is a pathologic diagnosis.

No meat, no treat – Medical “pearl”.

First, understand the concept of “differential diagnosis”. The term “differential diagnosis” refers to the many possible diagnoses that can cause a specific symptom (what the patient feels) or sign (what the doctor finds on a physical exam). Thus, for example, a headache can be caused  by literally dozens of potential diagnosis (see Table 14). Medical students are taught to construct lists of “differentials” for every symptom and sign and that compare these lists to one another (experienced physicians, like all experts often skip these steps and directly zero on the most likely diagnoses)`. Thus, for example, a patient who has a headache, stiff neck, nausea and vomiting will have lists of possible diagnoses for each of these symptoms; however, meningitis will be present on all of these lists. It will, therefore, become the leading potential diagnosis. However, until, a lumbar puncture provides patologic ( or microbiologic) evidence of meningitis, it will remain a potential but unproven diagnosis. It might be, that the spinal tap will surprise the physician with a heretofore not considered diagnosis.

The same is true of cancer diagnosis. Until a breast mass is biopsied it is only potentially a breast cancer. It may turn out to be an abcess, a lymphoma or a benign tumor located in the breast. Only after the pathology had been obtained, would the differential list translate into the final diagnosis.

If you hear hoofs behind you assume it is a horse; don’t assume it’s a zebra – Osler, explaining why the more common conditions would top the lists of differentials)

History of stem cell and bone marrow transplantation in cancer and leukemia

The history of stem cell research includes work with both animal and human stem cells. Stem cells can be classified into three broad categories, based on their ability to differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (e.g., identical twins). Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst and can form any of the over 200 different cell types found in the body. Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem cells.

A prominent application of stem cell research has been bone marrow transplants using adult stem cells. Among early attempts to do this were several transplants carried out in France following a radiation accident in the late 1950's. Since physicans could not isolate stem cells at that time, they transfused bone amrrow with stem cells in it. Autologous marrow means from the same individual while allogeneic marrow is provided by another individual. A bone marrow transplant between identical twins guarantees complete HLA compatibility between donor and recipient. These were the first kinds of transplants in humans, followed by autologous transplants. It was not until the 1960's that physicians knew enough about HLA compatibility to perform transplants between siblings who were not identical twins. In 1973 a team of physicians performed the first unrelated bone marrow transplant. In 1984 Congress passed the National Organ Transplant Act, which among other things, included language to evaluate unrelated marrow transplantation and the feasibility of establishing a national donor registry. This led ultimately to National Marrow Donor Program (NDWP) a separate non-profit organization that took over the administration of the database needed for donors in 1990. The 1990's saw rapid expansion and success of the bone marrow program with more than 16,000 transplants to date for the treatment of immunodeficiencies and leukemia.

Now that stem cells can be harvested from the blood, stem cell transpalntation has largely replaced bone marrow transplantation, although recent trials have revived an interest in bone marrow trnasplantation and its possible advantages over stem cell transplants. Adult stem cells also have shown great promise in other areas. Stem cell transplant for acute myelogenous leukemia. Philadelphia (PA): Intracorp; 2005. Various p. [50 references]

http://www.emedicine.com/med/topic3497.htm

Buckner CD: Autologous bone marrow transplants to hematopoietic stem cell support with peripheral blood stem cells: a historical perspective. J Hematother 1999 Jun; 8(3): 233-6