Therapy-Related Myeloid Neoplasms (t-MN) in 71 Patients Following Radiation Therapy (RT) Only,

Abstract 3522 Exposure to ionizing radiation has long been associated with the development of secondary malignant neoplasms including therapy-related myeloid neoplasms (t-MNs). We examined the clinical, epidemiologic, and cytogenetic characteristics of 71 consecutive cases of t-MN presenting to the University of Chicago between 1972–2011 in patients (pts) who received radiation therapy (RT) alone for a malignant or non-malignant disease; one-third had been treated for their primary disease at our institution. No subsequent chemotherapy had been given for the primary disease. 64 (90%) pts had had a primary solid tumor, 5 had had a primary hematologic malignancy (4 Hodgkin lymphoma), and 2 had received RT for non-malignant disorders (acne; hydatiform mole). Prostate and testicular cancers were the predominant primary tumors (n=27; 38%). Breast (n=15; 21%) and gynecological cancers (n=13; 18%, including ovarian, cervical, endometrial, and vaginal cancers) were also common. There were 36 women and 35 men; 50 white (70%), 10 African American (14%), 1 Asian American (1%), and 10 with unrecorded race/ethnicity. The median age at primary diagnosis was 64 years (range, 0–83 yrs). Pts with solid tumors were older at primary diagnosis (median, 66 yrs; range, 0–83) compared to pts with primary hematologic malignancies (median, 48 yrs; range, 32–67) or no malignancy (median, 22 yrs) (p= 0.01). Median latency from RT to the first confirmed diagnosis of t-MN overall was 67 months (interquartile range (IQR), 27–120 mos). Patients with a hematologic malignancy had shorter latency intervals (median, 25 mos; IQR, 18–50) compared to pts with solid tumors (median, 68 mos; IQR, 31–117) (p=0.017, Kruskal-Wallis test). Younger age at primary diagnosis correlated with longer latency intervals (p=0.0013, Spearman9s rank correlation test). However, this apparent association may be attributed in part to competing risk factors such as medical comorbidities and death in older pts prior to the development of t-MN. Gender was not associated with latency intervals. 59 pts had one or more clonal cytogenetic abnormality (83%) at diagnosis of t-MN; 12 (17%) had no detectable abnormality. Most common (38 pts, 54%) were translocation, loss, or deletion of chromosome 5 (n=19), 7 (n=8), or both (n=11). Ten patients (14%) had recurring balanced translocations previously reported in t-MN; 4 with inv(16) or t(16;16), 4 with t(15;17), and 2 with t(21q22). Eleven pts (15%) had other clonal abnormalities. No significant correlations were found between cytogenetics and age or type of primary diagnosis. Only 6 pts currently remain alive: 2 with inv(16), 1 with t(16;16), 1 with t(15;17), 1 with independent -7 and del(11q) clones, and 1 with a normal karyotype. The median time from diagnosis of t-MN to death was 10 months (95% confidence interval (CI), 7–14 mos). Pts with normal cytogenetics or recurring balanced translocations survived longer (log rank, p=0.0009). t-MN with clonal abnormalities of chromosome 5, 7, or both had a poor median survival of 7 mos (95% CI, 3–12 mos) compared to other cytogenetic groups. There was no association between age at diagnosis of t-MN and overall survival. Treatments given after the development of t-MN were individualized and variable, ranging from supportive care only to intensive chemotherapy and subsequent hematopoietic cell transplantation. We reviewed treatment records for 38 pts: 18 received low intensity treatment with best supportive care or participated in a phase I clinical trial; 20 underwent high intensity induction chemotherapy with or without hematopoietic cell transplantation. Pts in the low intensity treatment group had a median survival of 8 mos (95% CI, 3–11 mos) compared to pts in the high intensity treatment group who had a median survival of 14 mos (95% CI, 5–30 mos) (log rank, p=0.12). We conclude that t-MN following RT alone bears striking clinical and cytogenetic similarities to alkylator-associated t-MN with frequent clonal abnormalities of chromosomes 5 and 7, relatively long latency, and poor outcomes even with intensive therapy. However, some pts who develop t-MN after RT alone have recurring, balanced chromosomal translocations or normal karyotypes, and they have a better response to anti-leukemia treatment and longer survival. Disclosures: No relevant conflicts of interest to declare.