In this lecture, we will review leukemia in children. So leukemia is the malignant transformation and proliferation of hematopoietic cells. So we have acute leukemia which is a clonal expansion of immature precursors and we have chronic leukemia which is mature bone marrow components that are then becoming clonal. So, So symptoms can occur from a lack of normal bone marrow cell production or from accumulation of malignant cells in tissues that otherwise shouldn't have them.
So let's go through the epidemiology of leukemia in children. It is the most common pediatric malignancy. 30% of all newly diagnosed children with cancer have leukemia. boys typically get it a little bit more than girls. So we break down leukemia typically in kids into four major types.
By far and away the most common types are the first two. Let's go through these. First we have acute lymphoblastic leukemia.
Acute lymphoblastic leukemia or ALL is very common in kids. It's a proliferation of B and T cell lymphocyte precursors. like you can see here. It typically happens in children between the age of two and five, and again, boys a little more commonly than girls. Caucasians are at greatest risk for ALL.
Comparing that to AML, which is acute myelogenous leukemia. AML is a clonal proliferation of myeloid precursors. So there are many subtypes of of AML based on the morphology of the cells that are growing and the cytogenic translocations that have occurred which cause these cells to become clonal in nature.
There's a generally bimodal incidence in terms of when children get this disease. There's one peak in little tiny kids under two years of age and then again in adolescence. This for AML unlike ALL, the rate in boys and girls is about the same. And this is associated with some toxic exposures, also some genetic predispositions. For example, children with Down syndrome have a 50-fold increase in their risk for AML.
Remember that, Down syndrome and AML, strong association. Now we would switch gears to chronic disease and this is chronic myelogenous leukemia, which is less common in kids. This is an uncontrolled growth of myeloid cells and the incidence increases through childhood and adolescence.
Often these patients have a fusion protein, the BCR-ABL gene. This constitutively activates tyrosine kinase. The mutation in this translocation between chromosome 9 and chromosome 22 causes a continuously on activation of tyrosine kinase.
And lastly, we'll talk very briefly about the very mild form of leukemia, which is juvenile myelomonocytic leukemia or JMML. JMML is very rare. It's usually diagnosed before the age of three and the etiology is basically unknown.
It is associated however with a few genetic conditions like Down syndrome, neurofibromatosis, Lee-Fraumeni syndrome, and Fanconi anemia. So let's back off now and talk about what are the general symptoms of leukemia. If a child has leukemia, what do they look like?
Well, first of all, they're often lethargic. They have less energy to get through their day. Sometimes they have respiratory distress if there's a mediastinal mass that might be pressing on the trachea or something, but usually it's a nonspecific find of lethargy, some fatigue.
They may have increased bleeding if they're platelet counts are down and they may have increased rates of infections. Children may present with bone pain as their chief complaint when they have leukemia. Also, you may find on exam that they have fever, pallor from an anemia, tachycardia from an anemia, and bruising and petechiae from low platelet counts.
They may have lymphadenopathy, hepatosplenomegaly, or in boys, testicular enlargement. from some tissues growing with cancer cells in them, specifically the lymph and the splenic system. They may have facial swelling and wheezing and tachypnea if they happen to have a mediastinal mass. And they may have CNS involvement, which actually is not uncommon in ALL.
So how do we diagnose this problem? Well, the first mainstay of picking up anemia is the CBC. And frequently we will find signs on the CBC that something isn't right.
We usually will see what we say is two cell lines down. Sometimes one cell line down, but often that could be something else. For example, if a patient has thrombocytopenia only, this could be immune thrombocytopenic purpura, not cancer.
We would treat that very differently. But typically, they'll have more than one cell line down, which means they may have some anemia, some thrombocytopenia, some leukopenia, some leukocytosis at times with a very high white count, or neutropenia. You also may see a particular...
a particular type of cell called a blast. When you see a blast on a CBC differential, you should be highly concerned that that patient might have cancer and you should probably refer that patient to a hematology oncologist. In CML, we sometimes see very marked hyperleukocytosis with white counts in the 50 to 100 range and we often see normal myeloid precursors on those CBCs. Also in patients where we suspect they might have leukemia, we often will check a chemistry panel to look for signs of tumor lysis syndrome such as a high potassium or high phosphate. So we will check that, but that's not a great diagnosis mechanism, though rarely you may see it.
Also, we could do, if the patient specifically had CML, we could look for the BCR-able gene. That's usually a little bit later on. What radiology do we get? We usually get a chest x-ray.
And a chest x-ray can often show a large mediastinal mass like you can see in this patient with a widened mediastinum. To confirm the diagnosis, we will do a bone marrow aspiration and a biopsy to try and get some of that bone marrow tissue. That is then sent for cytology and you can actually identify the type of cancer off of cytology.
Additionally, we will often do a lumbar puncture to inspect for CNS involvement, especially in ALL. So, who is at highest risk when they have leukemia? Who are the high-risk patients? Well, children more than 10 years and less than 1 year are at higher risk. The children between 1 and 10 are at lower risk.
If their white count is very, very high, they're at higher risk. If they have a T-cell phenotype, they're at higher risk. And if they have cytogenic changes in their leukemia cells, they're at higher risk. And lastly, it makes sense if they're not responding well to therapy, they're at higher risk. So what is the therapy we're giving?
Well, it depends on the type of cancer obviously. In fact, there are complicated pathways and roadmaps that are established by multicenter groups that are how we treat these children in a very standardized way. So what you'll see is, And if you're taking care of one of these patients, they'll have a roadmap that'll say things like, for example, on day seven, they have to get intrathecal methotrexate. On day 14, they'll get something else.
It's a very prescribed pathway. We try very hard to follow the roadmap because it's been shown to have improved outcomes. So what is that roadmap involved? Well, in ALL, this is going to be a multi-agent chemotherapy with multiple agents, generally for two to three and a half years.
And also, they will get some pre-treatment. prophylactic intrathecal chemotherapy and or radiation to sanctuary sites. For AML, we will do multi-agent intensive chemotherapy for six to nine months, but some of these patients will warrant getting a hematopoietic stem cell transplant.
For CML, we're going to give single-agent therapy with tyrosine kinase inhibitors for the BCR-ABL gene and A hematopoietic stem cell transplant for a poor response, and for JMML, these patients oftenly require a bone marrow transplant. So what's the prognosis for these patients? Surprisingly good for ALL. More than 80% and even as high as 95% of patients in low-risk groups are going to survive their ALL.
This is a great accomplishment we have in pediatrics. For AML, it really depends on the subtype of AML, but it's probably around 50% survival rate. For CML, this is a lifelong disorder with tyrosine kinase inhibitor therapy. And for JMML, about survival of about 40% unfortunate with a bone marrow transplant which requires all the complications of bone marrow transplants.
But in general, most children have ALL and most children have a pretty good prognosis, it being cancer. So that's my review of leukemia in children. Thanks for your time.