There has been a dramatic improvement in the last 50 years among child acute lymphoblastic leukemia (ALL) in young leukemia patients. In the past all of them died within a short period of time. Now more than 70% will still be alive after 5 years and many of them will experience a normal life expectancy.
As mentioned above, this type of leukemia accounts for the majority of childhood leukemias.
The symptoms can all be explained on the basis of how much the bone marrow has been infiltrated with an abnormal white blood cell (lymphoblast). The more these abnormal white blood cells take over in the bone marrow the more this causes a low red blood cell count and a low platelet count. That’s the reason why there is pale skin color (anemia), weakness, lassitude, poor appetite and weight loss (due to cachexia).
There can be bleeding from minor bruises, petechiae (pin size blood spots from low platelet count) and purpura (an accumulation of blood blisters often on the lower legs). There are more frequent infections due to a weakened immune system with lowered immune cells (lymphopenia) due to the invasion of the bone marrow, which prevents the immune cells from maturing and multiplying normally. Finally, as the lymphoblasts invade other soft tissue organs throughout the body, there will be signs of liver enlargement and spleen enlargement. When there is infiltration of the periosteum (the skin surrounding the bones), symptoms of bone pain occur with a limp or walking problem.
A child with acute lymphoblastic leukemia needs to see the doctor right away as the disease could very quickly take a turn for the worse.
Leukemia blood tests need to be done and the best is to admit the child to a special ward at the hospital where there is reverse isolation, meaning that the child is being protected from hospital bacteria until the function of the immune system is stabilized.
A pediatrician should be involved in the care and if available, a pediatric hematologist should also be consulted. The tests that will be ordered first are a battery of blood tests. These show a high white blood cell count, a low hemoglobin and low platelet count. The blood smear shows 85% or more lymphoblasts. The next test will be a bone marrow aspirate and if this is inconclusive (as it occasionally may be) a bone marrow biopsy may be necessary.
In preparation for chemotherapy, which destroys a large number of the cancerous lymphoblasts, the function of liver and kidney will also have to be assessed with special blood tests. The destruction of the cancer cells leads to high uric acid and this needs to be metabolized and excreted through the kidneys without causing kidney damage or getting kidney stones. Lung x rays and a CT or MRI brain scan often are also done to rule out involvement of the lungs and brain. In the 1950’s and 1960’s it became apparent that recurrences often came from the central nervous system, where the cytotoxic drugs did not go because of the “blood-brain-barrier”.
Treatment of ALL has become so sophisticated that it would be best to be treated in one of the big Cancer Clinics or in a Children’s Hospital with a hematologist who has an interest in leukemia. In order to assess the risk further laboratory methods are used by the specialist. You will hear terms such as “immunotyping”, “cytogenic analysis” and “genotyping” to name but a few. This way one can classify ALL into high risk or low risk for recurrence based on prior studies.
The therapy is divided into the following categories (click on + to open sections).
Remission inductionThe concern here is to stop the ALL from multiplying and quickly bring the uncontrolled ALL under control. Prednisone and vincristine are the traditional drugs used at this stage. However, it has been shown that this combination only would lead to 80% to 90% remission and this would not be acceptable any more in view of the fact that by addition of L-asparaginase or daunorubicin the remission rate can be increased to 90% to 100%. Sometimes a fourth induction agent, anthracycline daunorubicin, is added, which improves remission rates even in light of very poor situations. Using chemotherapy like this, a remission usually lasts for 4 weeks.
Central nervous system prophylaxisInitially radiotherapy was used to the brain in an attempt to prevent that microscopic leukemia in the brain would spread to the rest of the body again when chemotherapy was finished. However, long-term studies revealed significant central nervous system damage as a result of scarring of the brain tissue from the radiation. Since then chemotherapy combination with triple chemotherapy using hydrocortisone, cytarabine and methotrexate, partially intravenously and partially intrathecally (via a needle into the cerebrospinal fluid), has given as good or better results than the original brain irradiation method.
Consolidation and maintenance therapyWithout further therapy most patients would relapse within 1 or 2 months. It is because of this that a consolidation therapy was introduced. Methotrexate and 6-mercaptopurine are the two chemotherapeutic agents used for this. 6-mercaptopurine is given daily and methotrexate is given once or twice weekly. Sometimes other chemotherapeutic substances are added when some of the cell markers or genetic tests show that the leukemia is particularly aggressive. Nowadays in a case like this the specialists often decide to do again a "reinduction" and "reconsolidation" therapy and possibly do several cycles of this until the leukemia stays in remission. After 2.5 to 3 years of the consolidation therapy the treatment regimen is complete. When patients have completed this full course, the prognosis for these patients is good with about 80% of them staying disease free. After 4 years of no relapse and "off" treatment, there is now almost no danger of a relapse.
RelapseWhen leukemia comes back despite initial chemotherapy after a certain interval, this is called a "relapse". "Remission" is the state when the leukemia is under control. So, when a relapse is evident all the symptoms that were there initially are starting all over again. Blood tests have to be done again. The specialist must be notified right away that there is a relapse. At this stage a quadruple chemotherapeutic drug regimen is usually given such as vincristine, prednisone, L-asparaginase and daunorubicin. This usually produces remission rates in 90% of patients. The patient has to be examined and tested very carefully to see whether or not there is involvement of the central nervous system or involvement of the testicles with the leukemia, two areas that are often affected beside the bone marrow. Should there be involvement of these organs special treatment for the central nervous system has to be given again as mentioned above. For testicular involvement bilateral radiation of the testicles has to be done. Unfortunately this will lead to sterility, but can save the life of the boy or young man.
The role of bone marrow transplantA bone marrow transplant has been employed in the treatment of difficult ALL's since the early 1980's. A bone marrow transplant can be obtained from about 1/3 of siblings whose bone marrow cells are compatible, which means that in these cases this treatment can be undertaken. As with each relapse of ALL the long-term survival goes down by about 20%, the recommendation of authorities in the field is to use a bone marrow transplant during the second remission. The Seattle bone marrow transplant group has reported a 40% or more long-term disease free survival when the transplant was done after the second remission with ALL. Although this may not sound very encouraging, in the past all of these patients died, so that these figures do show progress.