The Hematologist

July-August 2017, Volume 14, Issue 4

Disparities of Adolescent and Young Adult Patients in the Treatment of Malignant Hematologic Diseases

Leidy Isenalumhe, MD, MS Clinical Hematology/Oncology Fellow
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Published on: July 01, 2017

The Adolescent and Young Adult (AYA) Progress Review Group (PRG) defines the AYA cancer population as patients ranging from 15 to 39 years of age. An estimated 69,000 AYA individuals are diagnosed with cancer each year — six times more than children younger than 14 years.1 The AYA age demarcation was established as a high-risk population after data from the Surveillance, Epidemiology, and End Results (SEER) study showed a lack in improvement in survival for patients with many forms of cancer.2,3 The most common malignancies are leukemia, lymphoma, germ cell tumors, and central nervous system tumors among 15 to 24 year olds, with the incidence of breast cancer, colorectal cancer, and melanoma increasing among older AYA patients1 (Figure).

In 2007, the AYA PRG released a comprehensive guide explaining the disparities experienced by AYA cancer patients that have led to their poor outcomes and lack of progress throughout the years.2 These disparities include lack of health insurance, differences in disease biology, delay of diagnosis and treatment, increased toxicities, lower socioeconomic status,4 and overall lack of awareness in the medical field as to the special needs of this population (Table 1).

Table 1. List of the Disparities Experienced by AYA Hematology-oncology Patients
Access to health care
Psychosocial stressors
Delay in diagnosis
Delay in treatment
Treatment site
Reduced rates of clinical trial enrollment and treatment standardization
Increased toxicity

The goal of the AYA PRG was not only to introduce and educate the medical field about this high-risk population, but also to start a systematic mitigation of the disparities. Since the release of the PRG guide, progress has been made, including an increase in AYA-specific scientific peer review publications, formation of AYA oncology programs, development of AYA-specific national workshops and committees, development of clinical trials targeting AYAs, and expansion of inclusion criteria to include AYAs.4,5 Additionally, the European Cancer Registry (EUROCARE) and NCI SEER data have reported improvement in survival rates for the AYA population.5,6 Despite some improvement in survival, AYAs still have lower five-year relative survival rates for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, Ewing sarcoma, and breast cancer compared with children and older adults.6 Notably, the incidence of all invasive cancers continues to increase in AYAs compared with any other age group.7

Although many common malignancies overlap in younger and older patients, research advances in ALL, breast cancer, colorectal cancer, sarcoma, and melanoma have identified age-dependent differences in disease biology within the same malignancy.8,9 ALL is the most common malignancy in AYAs with a continued increase in incidence in the past 10 years, and still remains the leading cause of AYA cancer deaths.7-10 The overall survival (OS) for AYAs with ALL is 52 percent, compared with 90 percent in children.6 Age-related genetic and biological variation in ALL are well established and likely contribute to the continued poor OS. AYA patients diagnosed with ALL have a higher frequency of genetic alterations that are associated with poor prognosis, such as Ph+ ALL, Ph-like ALL, hypodiploidy, and iAMP21 (Table 2).7-9,11,12 Recent epidemiological data have indicated that AML patients between the ages of 15 and 39 years had a much lower five-year OS compared with younger patients (50% and 66%, respectively), and age is an established poor prognostic factor in adults with AML.6,7,13 The presence of specific genetic abnormalities also seems to differ between pediatric and AYA AML, but data are limited due to low number of AYAs treated on AML clinical trials.13 Compared to children younger than 16 years, AYAs age 16 to 21 years were more likely to have normal cytogenetics, favorable prognostic markers such as NPM1 and CEBPA, and a higher incidence of acute promyelocytic leukemia, but they were also more likely to carry unfavorable markers such as FLT3-ITD (Table 2).13

Table 2. Differences in Disease Biology of Hematologic Neoplasms in AYAs
 Positive prognostic factorsNegative prognostic factors
  • Higher incidence in younger patients
  • Higher incidence in younger patients
Ph-like ALL
  • Age 1-9 years: 10%
  • Age 16-20 years: 21%
  • Age 21-39 years: 27%
KMT2A rearrangements
RAS mutations
  • Germline variants are associated with predisposition to AYA ALL
Early T-Cell Precursor ALL HOX+
  • Higher incidence in AYA
Acute Myeloid Leukemianormal cytogenetics, NPM1 and CEBPA
  • Higher incidence in AYAs
  • Incidence increases with age

Abbreviations: ALL, acute lymphoblastic leukemia; AYA, adolescent and young adult.

In addition to biological differences in disease, socioeconomic factors such as lack of health insurance are associated with advanced stage at presentation, delay in diagnosis and definitive treatment, and increased mortality.14-16 Persons between the ages of 18 and 34 years are more likely to be uninsured compared to other age groups.16 In AYA patients with Hodgkin lymphoma, having public health insurance was associated with an increased risk of advanced disease at time of diagnosis.17 Having no insurance or public health insurance, as well as low socioeconomic status, act as barriers to treatment at National Cancer Institute (NCI) –designated comprehensive cancer centers (CCCs), where the outcomes are superior to those of other institutions.18,19 Dr. Julie A. Wolfson and colleagues reported on the inferior outcomes of AYA patients with ALL and AML who were treated at non–NCI-designated CCCs or Children’s Oncology Group (COG) centers. Age, lack of private health insurance, and nonwhite race/ethnicity were additional barriers to treatment at CCC/COG centers. AYAs treated at CCC/COG centers had similar outcomes compared with children treated at CCC/COG sites, suggesting that treatment at such centers may have attenuated the poor outcomes reported in AYAs with ALL (<30 years of age) and AML (<22 years of age).20 There are many more factors that contribute to the lag in progress of AYAs that are beyond the scope of this article.

The following quote from English philosopher John Locke summarizes what we have learned thus far and what we need to do to move forward: “The improvement of understanding is for two ends: first, our own increase of knowledge; secondly, to enable us to deliver that knowledge to others.”

Recently the NCI National Clinical Trials Network (NCTN) underwent major restructuring, with the nine adult cooperative groups merging into four (Alliance Oncology, Eastern Cooperative Oncology Group/American College of Radiology Imaging Network [ECOG-ACRIN], NRG Oncology, and Southwest Oncology Group [SWOG]). Such changes benefit the AYA oncology community by expanding access to clinical trials for this group, and broadening the potential to form intergroup trials with the expertise of both pediatric and adult hematologist/oncologists. In November 2013, the COG AYA committee and the SWOG AYA committee formed the NCTN AYA Working Group with the primary objectives of increasing enrollment of AYA patients onto NCTN trials and developing AYA-focused clinical trials.21 To further spread the knowledge we have obtained in the past 10 years, hematology/oncology professionals must also structure targeted educational opportunities for physicians.

Greater than 25 percent of AYA patients are treated at community centers.22 The NCI community oncology research program (NCORP) was established to expand access of NCTN trials to patients treated in the community and patients afflicted by health disparities.21 Additionally, as the increase in AYA oncology programs continues,5 we must also lead the charge for recruiting and retaining AYA-focused hematology/oncology professionals. This can be in accomplished in various ways, such as dual training in internal medicine or pediatrics followed by a combined pediatrics and adult hematology/oncology fellowship, or additional AYA-focused fellowship training after initial certification in adult or pediatric hematology/oncology.

The AYA population is a unique, high-risk group of patients facing malignant diseases at an age where they are transitioning to independence. It is a time where they can emotionally comprehend the burden of their disease, yet may not be as established socially, financially, and emotionally as their adult counterparts, and may not have the comparable support structure as younger patients. Although we should be proud of the progress that has taken place in the past decade, we cannot lose momentum — we need to build the strong and sustainable foundation that our AYA patients deserve.


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Conflict of Interests

Dr. Isenalumhe indicated no relevant conflicts of interest. back to top