Children, Adolescents, and Young Adults With Leukemia: The Empty Half of the Glass Is Growing

Abstract

On the basis of survival trends in the acute lymphoblastic leukemia (ALL) trials conducted by the Children's Oncology Group (COG) between 1990 and 2005, Hunger et al 1 predict the 10-year survival of children with ALL entered onto COG trials between 2006 and 2010 will approach or exceed 90%. They also "believe that it is extremelyunlikelythattherewillbeasignificantincreaseindeathsbeyond 5 years for patients diagnosed in 2000-2005." 1(p1668) They chose to compare their results with data from the original nine geographical regions of SEER (SEER9), a 9.5% sample of the United States, in concluding that the 5-year COG survival rate was 3.9% higher than the national average for patients younger than age 15 years and 13.4% higher for 15-to 19-yearolds. The focus of their discussion was on how to help "US children, adolescents, and young adults with ALL who are treated on COG clinical trials" 1(p1668) and not expected to survive. 1 What about patients not treated on COG protocols? Figure 1 compares the death rate after diagnosis of ALL between 2000 and 2005 for COG enrollees age 0 to 21 years derived from Figure 1 of the report by Hunger et al 1 (solid gold line) with the data from 18 geographical regions (SEER18) 2 released on April 15, 2012 for 28.7% of the US population for patients age 0 to 19 years (shaded gray line). The dotted blue line represents an extrapolated cohort of US patients younger than age 20 years who,deducingfromtheCOGandSEER18curves,werenotenrolledonto COG studies. Not only has the death rate among those not enrolled been more than twice that of COG enrollees, exceeding 25% by 8 years, but the rate of increase after 5 years from diagnosis in the non-COG cohort appears to be accelerating instead of slowing. Moreover, at least 9,000 American patients younger than age 20 years, representing approximately 60% of all persons diagnosed with ALL in the age group, were not enrolled ontoCOGtrialsbetween2000and2005.Thisnumberincludesthosewho were enrolled onto clinical trials elsewhere, such as the St. Jude Children's Research Hospital and the Dana-Farber Cancer Institute Consortium, andwho,ifremoved,wouldrendertheresultsfortherestofthenon-COG patients in our country even worse. Also ominous is the trend in the proportion of patients with ALL not treated on active COG protocols. From the data in the report by Hunger et al, 1 the average annual accrual to COG ALL studies of patients younger than age 21 years decreased from 1

Racial disparities in the survival of American children, adolescents, and young adults with acute lymphoblastic leukemia, acute myelogenous leukemia, and Hodgkin lymphoma

“…The BCR‐ABL genotype occurs in <3% of children and in up to 26% of AYAs with ALL . Nearly 50% of children with ALL have favorable genotypes such as a TEL‐AML translocation, whereas approximately 10% of AYAs do . In patients with AML, FLT3‐ITD mutations increase in frequency with age and are associated with a poorer prognosis in all age groups .…”

Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma

“…In addition, they have generated more than 50 new human‐murine xenograft and primagraft models of ALL to further dissect the biologic and functional consequences of novel mutations being discovered in this disease and to serve as preclinical animal models to test potential therapeutic interventions. By using gene expression profiling (GEP) and other genomic methods, this group first discovered pediatric ALL patients who had a “ BCR ‐ ABL1 –like” or “Ph‐like” gene expression signature that was described simultaneously by a group from the Netherlands and is associated with a significantly increased risk of treatment failure and death. Each of these different names for the same phenotype or GEP reflects the similarity of this novel GEP to that of ALL containing the classic Ph chromosome translocation (t[9;22] or BCR ‐ ABL1 ).…”

Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) With Acute Myeloid Leukemia (AML)

“…AYA with leukemia are a unique group of cancer patients that may exhibit distinctive patient and disease characteristics compared to other age groups and other cancer patients 8-10 . Much has been reported about the prognosis of AYA with acute lymphoblastic leukemia (ALL) 11,12 .…”