Myelodysplastic Syndromes in Adolescent Young Adults (AYA)
Authors: Grabska Joanna (Asia) , Shah Bijal D. , Al Ali Najla H. , Padron Eric , Ramadan Hanadi , Lancet Jeffrey E , List Alan F. , Komrokji Rami S. 
Published: October 2019

Abstract
Introduction:
There has been little improvement in cancer survival of adolescent and young adult (AYA) patients, ages 18-39, possibly reflecting different disease biology in this subgroup. Myelodysplastic syndrome (MDS) is mainly a disease of the elderly. The characteristics, outcomes and response to treatment are not well described among AYA population.
Patients and Methods:
Retrospective review of patients from the Moffitt Cancer Center MDS database. We compared baseline characteristics and outcomes of AYA population to older patients. Descriptive statistics were used for baseline characteristics. Chi-square test was used for categorical variables, and t-test for continuous variables comparison. Kaplan-Meier estimates were used for overall survival (OS), and cox regression method for multivariable analysis.
Results:
We identified 51 AYA and 1,897 older MDS patients. Table-1 summarizes baseline characteristics. More females and Hispanics were noted in AYA group. The AYA patients had higher risk disease, more circulating myeloblasts and more hypoplastic MDS. Autoimmune disorders were more prevalent in older patients.
The median OS was 47 months (mo) in the AYA group versus 40 mo in the older group (p 0.26). The median OS was 47 mo versus 56 months in lower risk (low and intermediate-1(int-1)) IPSS MDS AYA group and older group respectively (p 0.46). In the higher risk IPSS group (int-2 and high), median OS was 82 mo in AYA group compared to 17 mo in older group (p 0.001). Thirty individuals were transplanted in the AYA versus 241 in the older group. The median OS for transplanted patients was 55 mo in the AYA group and 46 mo in the older (p 0.4). Whereas, in the non-transplanted patients median survival was 31 months for AYA and 39 months for the older group (p 0.9). The rate of AML transformation was 37% versus 28% in AYA and older group respectively (p 0.17). No difference in use or response to hypomethylating agents was observed. Lenalidomide therapy was seldom used in younger patients.
In AYAs, poor karyotype was the only variable strongly associated with worse outcome. Fifteen patients had poor risk karyotype. The median OS was 47 months, not reached and 29 months among patients with good, intermediate and poor risk cytogenetics, respectively (p 0.035)
Conclusion:
MDS is rare and tends to be more aggressive in the AYA population. The karyotype was the most important prognostic factor. The differences in underlying disease biology should be further explored. Allogeneic stem cell transplant offered younger patients best outcomes.
Table 1. Baseline characteristics of AYA and Older Patient Characteristic AYA (18-39) (N= 51) Older Patients (> 39 years old) (N=1,897) P value Gender Female 25 (49%) 655 (34.5%) 0.025 Race White Black Hispanic Other 34 (66.7%) 2 (3.9%) 13 (25.5%) 2 (3.9%) 1,736 (91.5%) 47 (2.5%) 57 (3%) 41 (2.2%) 0.000 t-MDS Yes 10 (19.6%) 359 (18.9%) 0.902 WHO Subtype RA RARS RCMD Deletion 5q RAEB-1 RAEB-2 AML CML MDS-U MDS/MPN 3 (5.9%) 1 (2%) 22 (43.1%) 0 (0%) 11 (21.6%) 10 (19.6%) 0 (0%) 0 (0%) 1 (2%) 2 (3.9%) 196 (10.4%) 151 (8%) 583 (30.8%) 51 (2.7%) 372 (19.7%) 336 (17.7%) 1 (0.1%) 60 (3.2%) 44 (2.3%) 94 (5%) 0.188 IPSS Lower risk Higher risk 28 (59.6%) 19 (40.4%) 1,264 (68.2%) 590 (31.8%) IPSS-R Very low/low Intermediate High/very high 13 (30.1%) 14 (32.6%) 16 (37.3%) 826 (45.3%) 394 (21.6%) 602 (33%) Hypoplastic BM Yes 11 (23.4%) 178 (9.8%) 0.009 LGL clone Yes 0 (0%) 159 (8.4%) 0.033 Autoimmune disease Yes 8 (15.7%) 500 (26.4%) 0.055 Karyotype Good Intermediate Poor 24 (50%) 9 (18.8%) 15 (31.3%) 1120 (60.4%) 300 (16.2%) 434 (23.4%) 0.324 Peripheral Blasts Yes 14 (29.8%) 246 (13.2%) 0.003 RBC Transfusion Dependent 36 (70.6%) 1274 (67.3%) 0.372

Disclosures
Shah: Seattle Genetics: Research Funding; Rosetta Genomics: Other: Grant support; Acetylon: Other: Advisory board; Plexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Other: Advisory board, Speakers Bureau; Bayer: Honoraria; Celgene: Other: Advisory board, Speakers Bureau; DeBartolo Institute for personalized medicine: Other: Grant support. Lancet:Pfizer: Consultancy; Kalo-Bios: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding. List:Celgene Corporation: Honoraria, Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding.