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The Growth of Pediatric Oncology and Optimal Care for Pediatric Acute Lymphoblastic Leukemia

August 07, 2019

BleyerJournal of Clinical Pathways spoke with Archie Bleyer, MD, former chair of the Childrens Cancer Group and one of the founding fathers of pediatric oncology, to explain the current state of pediatric oncology within the context of the historical timeline of guideline development in this population. Dr Bleyer also explains the dilemma of treating adolescent and young adult patients with ALL in concordance with the recent NCCN guideline update for this disease.

In your opinion, how far have clinical guidelines come for pediatric and young adult oncology patients in the past 30 years?

Dr Bleyer: In general, the impact of the recent National Comprehensive Cancer Network (NCCN) ALL guidelines at the pediatric cancer centers across the country will be minimal. The reason for that is they have already been working together for almost 60 years prior to the guidelines having been established by the NCCN.

The Childrens Cancer Group—which is a group that I was most involved with—started in the early 1950s. It has been approximately 65 years that we have been working together to understand as a community of pediatric cancer specialists how to treat, diagnose, manage, and follow children with cancer.

When the NCCN guidelines came along three or four decades later, we had already made so much progress in this area that the NCCN guidelines for us were largely unnecessary. When the Pediatric Oncology Group was founded and added to the Children's Cancer Group, we collectively covered just about every pediatric cancer center and even smaller centers that treated pediatric cancer in the US.

We were already working together. We had national meetings of the cooperative groups two to three times a year and multiple regional meetings. The guidelines thus have had only a minimal impact on pediatric oncologist.

The reason we worried about the NCCN guidelines for pediatric cancer was the overlap between the adolescents and young adults being treated by medical oncologists at adult treatment centers. Medical oncologists needed the NCCN pediatric guidelines because they were not accustomed to treating the young adults with pediatric types of cancer. The guidelines really mattered because now, they could look at the guidelines and treat their patients based on how pediatric oncologists had been treating these patients for many years.

The NCCN guidelines are exceedingly important in the adult private practice environment, where more than 80% of adult patients with cancer are treated and approximately 90% of young adults with cancer are treated. The guidelines are absolutely critical; they are presented weekly at tumor boards in communities and private practice environments, usually at the hospital that is supporting cancer therapy and therefore has a tumor board that can meet and review the guidelines. Most often, the guidelines are portrayed on a screen when medical oncologists, surgical oncologists, the radiation oncologists assemble so they can see what is going to be recommended before they even begin discussing a patient.

I cannot imagine how the US would take care of those young adults with pediatric types of cancer without those guidelines. It is striking how little those guidelines mean to pediatric oncologists yet how much they mean to the adult‑treating oncologist, especially those treating young adults.

In recent years, there has been a wave of pediatric oncology guidelines from multiple organizations, including one from NCCN on pediatric acute lymphoblastic leukemia (ALL). Are these guidelines relatively in concordance with one another, or is there disagreement about optimal pediatric patient care?

Dr Bleyer: Let us focus on the pediatric ALL guidelines that were released recently. I have been involved with treating children with ALL as well as young, middle‑aged, and older adults with ALL since 1969. The original therapies that began to cure children with ALL came about in the early 1970s.

The Childrens Cancer Group already had multiple decades of experience at this time; the group had been conducting clinical trials in ALL as early as the 1950s and thus had a head start with understanding how to treat the most common pediatric cancer.

In the six decades to follow, there have been more than one hundred clinical trials for children and adolescents with ALL, not for just those newly diagnosed, but also relapsed patients, multiply relapsed patients, and those treated with phase I protocols. For newly-diagnosed ALL, the Childrens Cancer Group itself tested 134 regimens in 52 prospective randomized controlled trials in 20,235 children and adolescents. When you compare that number with the much smaller number of clinical trials that have been done in adult patients with ALL, the difference is staggering. Thus, you can imagine how much more was learned about children with ALL than adults with ALL.

Several decades ago, the idea of using applying what was learned in children with ALL for young adults with ALL was an obvious need. In the 1970s, 1980s, and especially in the 1990s, the Childrens Cancer Group and the Pediatric Oncology Group promoted what they had learned to be used in young adults. When we tried to apply the pediatric regimen to adult patients, there was pushback because the pediatric oncologist had to assume a central role in helping the adult oncologist, the latter of whom had to agree that his/her patient could benefit from a different treatment than had been administered.

The adult treatment regimen that had been primarily used was much simpler. How could the adult-treating oncologist take the time and effort to learn a more complex regimen? The proportion of their patients who had ALL was much smaller than it was for pediatric oncologists for whom ALL was the most common disease they treated.

Some of the adult oncologists wanted to transfer their young adult patients to the pediatric cancer center. However, this was not an easy to do because most pediatric centers did not accept patients over the age of 18 years.

Then, there was the coordination challenge between pediatric and adult-treating oncologists. That took considerably extra effort and was often an issue because the practices were often not geographically close to each other.

Furthermore, there was some concern—though this turned out to be erroneous—that a pediatric oncologist was not licensed to take care of a young adult, and vice versa.

Do these issues occur in other countries, or are they exclusive to the US?

Dr Bleyer: In ALL, it was clear that for young adults, the adult regimen is not as effective as the young adult pediatric regimen. This challenge has been addressed more adequately outside the US and has been especially effectively in Europe.

How can other countries in the world accomplish something and the US cannot? What it comes down to is collaboration, cooperation, communication, and documentation. These are more problematic in the US than elsewhere, at least as currently evidenced for adolescents and young adults with ALL.

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