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, Spearman's 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.