Pediatric Leukemia: The Latest Updates and What PCPs Can Do To Help

Leukemia is the most common form of pediatric cancer affecting about 3,800 children each year. In honor of Childhood Cancer Awareness month, we talked with Dr. Andrew Place, a pediatric hematologist and oncologist with the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, to hear about the latest advancements on treating this disease and what PCPs can do to support their patients and their families through this difficult process.

Dr. Place is the Co-Director of the Hematologic Malignancies Center and a Senior Physician at the Dana-Farber Cancer Institute. In addition, he is the Chief Medical Officer of the Institutional Centers for Clinical and Translational Research (ICCTR) at Boston Children's Hospital and an Assistant Professor of Pediatrics at Harvard Medical School.

What are some of the red flags PCPs should look out for to signal their patient may have leukemia?

The symptoms and signs of acute leukemia can be subtle and can be similar to other common non-malignant childhood conditions, such as common viral illnesses. Leukemias are cancers of the blood cells and these malignancies most commonly develop in the bone marrow. As the leukemia expands, the bone marrow is no longer able to make the normal cells of the blood – red cells, white cells and platelets. Abnormal numbers of these blood components result in some of the classic symptoms of leukemia: fatigue and pallor from decreased red cells, fevers and infections from decrease while blood cells and abnormal bleeding, rash or easy bruising from decreased platelets. Children with leukemia can also develop bone pain and a limp as a result of the expansion of the leukemia in the bone marrow space. Additionally, some children will also present with swollen lymph nodes.

The most common type of leukemia in children, Acute Lymphoblastic Leukemia (ALL), has its peak incidence between age 2 and 4 years. All pediatricians should think about this diagnosis in the setting of a previously healthy child who presents with the aforementioned symptoms. That said, most children who go to their pediatrician with some of these symptoms are unlikely to present with cancer – for example, a child with pallor, fever and rash is much more likely to have a viral infection than leukemia. That said, because acute leukemia can progress rapidly, pediatricians should be familiar with the common presenting symptoms of this common childhood malignancy.

An important point to note is that children with leukemia can function almost normally until the blood abnormalities become quite severe. They are able to compensate quite well because of the overall health of their organs – heart, lungs, kidneys, for example.

What should a PCP do if they see these symptoms?

The most important first step for a pediatrician who has a concern for a new leukemia is to get a Complete Blood Count (CBC) with a differential.. Most pediatricians are very capable of interpreting a CBC and identifying decreased numbers of platelets, white cells and red cells. Additionally, this test can identify leukemia cells that have spilled into the blood from the bone marrow. Significant decreases in two or more blood cell types, or the presence of malignant leukemia “blasts” warrant immediate referral to a pediatric emergency room.

It is important that the ED to which the patient is referred has pediatric expertise. Pediatric-trained ED doctors are familiar with the symptoms and initial management of a patient suspected to have leukemia. Pediatricians should also familiarize themselves with a pediatric cancer center to which they can refer patients. A simple phone call can provide assistance to the pediatrician caring for a patient that may have leukemia. Nearly all pediatric cancer centers have pediatric oncologists on call to assist with proper management of a child suspected to have leukemia.

What are the latest trends in pediatric leukemia? Have there been any significant advancements recently?

In pediatrics, the two main types of leukemia are Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML). These are different biological diseases and also have different treatment regimens and outcomes. ALL is the most common type of leukemia and overall outcomes are quite good as a result of decades of clinical trials. Nearly 90% of children diagnosed with ALL today are expected to be cured. In AML, outcomes are somewhat less favorable, and research continues to identify new strategies and drugs to improve survival rates.

In the last several years, there have been several very exciting new immunotherapies that were first studied in patients whose leukemia had relapsed and increasingly, these exciting agents are now being incorporated into the treatment of newly diagnosed patients. The new agent that has been discussed widely in the popular press, is a drug called Kymriah that has been approved by the FDA for the treatment of relapsed B-cell ALL. Kymriah is a therapeutic made from a patient’s own T-cells that are genetically engineered to seek out and destroy leukemia cells. This type of therapy is known as CART-T cell therapy. Kymriah is particularly exciting because it worked very well in patients that had no other treatment options. Therefore offering a chance of cure for patients who were previously incurable.

Two additional immunotherapeutics – blinatumumab and intozumab – are modified antibodies that specifically target proteins on the surface of leukemia cells. These drugs are highly effective and are also much less toxic than standard intensive chemotherapy. This type of targeted therapy has already revolutionized the treatment of relapsed ALL and these drugs are now moving into trials treating newly diagnosed children with B-ALL in hopes of improving cure rates and decreasing long term-treatment related side effects. Just five years ago, the field was excited about a drug called clofarabine - a non-specific cytotoxic agent (basically a poison) - and now we seldom consider using that drug.

For patients in more remote areas that are interested in experimental therapies, but have limited access, where can PCPs find resources on trials that may be available to their patients? 

We are fortunate in the United States that there are several cooperative groups and consortia that focus on developing experimental therapeutics in relapsed leukemia. These groups include the Children’s Oncology Group, the TACL Consortium and multi-institutional studies run through one or more of the larger pediatric cancer centers, such as the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. These groups collaborate with numerous childhood cancer centers so that the trials can be closer to the patients that need them. There is a lot of information about trials for pediatric patients with cancer at

I really encourage families to discuss the possibility of seeking a second opinion or pursuing a clinical trial option with either their PCP or oncologist. Due to the complexity of the diseases and their treatment, providing accurate and complete medical information is a critical component of any referral. This information allows us to match the best therapy to the patient’s needs. We really try not to put the burden of record collection on the family as they are already dealing with realities of caring for a child with cancer.

Can these interventions be delivered remotely or does the patient have to be on-site?

Normally, for early phase clinical trials in children, the patient will have to come onsite. Unfortunately, there are only about a dozen pediatric cancer centers with deep expertise in early phase trials, so travel may be necessary. For later phase trials, they are typically available at additional centers that may be more conveniently located.

We could have a lengthy conversation about improving access to early phase clinical trials. Not only would this allow better access to novel therapies, increasing the diversity of study subjects provides additional information about a drug’s effectiveness and tolerability in a group that is more representative of the larger population of childhood cancer patients. We recognize, for example, that access to early phase trials may be easier for wealthier families who have the means to travel extended distances. Because the results of Phase I trials are used to determine which drugs are ultimately tested in larger studies, increasing the diversity of study subjects may help us better identify drugs to be brought forward in later phase studies.

What can a PCP do to help support their patient through both the initial conversations with the family and also throughout the management of the disease?

For a pediatrician, having a child in their practice diagnosed with cancer may only happen 1 or 2 times in an entire 30-year career because of the rarity of the condition. Not only is a cancer diagnosis traumatic for families, but this can be an emotional time for their primary care providers, too. Sometimes pediatricians may wonder if they should have made the diagnosis sooner and we try and reassure them that in the case of leukemia, it is very common for the family to be seen a few times before blood work is obtained that reveals a problem. Also, because leukemia is a cancer of the blood, the malignant cells are assumed to be widely spread no matter how early in the disease process the diagnosis is made.

It is also important to stress that the pediatrician is still the medical provider for all the children in the home. Since most childhood leukemias are diagnosed in grade school, there are often other siblings in the home and the pediatrician should maintain their role in caring for siblings. Leukemia treatment can last anywhere from 6 months to 3 years. As a patient gets into the later phases of treatment (which tend to be less intensive), they can begin to re-integrate with their pediatrician for checkups and start to re-establish care. It is often helpful for the pediatrician to receive notes from the pediatric oncologist in order to stay up to date with disease response and any treatment related complications. Once the patient completes therapy, pediatricians can be helpful in monitoring for late effects of treatment. For example, children who receive radiation therapy as part of their cancer treatment are at risk of developing skin cancers and endocrine problems. The pediatrician can definitely participate in exams and evaluations to monitor these side effects. If the pediatrician needs more support or guidance, many cancer centers have survivorship programs which can assist with additional evaluations.

We understand that pediatricians want to hear about their patients’ treatment and when we call them to ask for help with a lab draw or administering a flu shot closer to home, these practices are nearly universally eager to assist.

RubiconMD is proud to partner with Boston Children’s to support clinicians and patients. For more information on pediatric leukemia, visit the Dana-Farber/Boston Children's resource page.