The Clinical Course of Head and Neck Cancer in Patients with Chronic Lymphocytic Leukemia
Authors: Maybury Aaron D , Hochberg Ephraim P. , Wirth Lori J , Abramson Jeremy S. , Emerick Kevin S , Michaelson James S. , Toomey Christiana E. , Cibor Kristina , Diephuis Brad , Bush Devon 
Published: October 2019

Abstract
Abstract 4741

BACKGROUND.
Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary malignancies, including squamous cell cancers (SCC) of the Head and Neck (HNC). While cutaneous SCC have been shown to behave more aggressively in the setting of CLL, little information exists on the clinical course and outcome of SCC of the oral cavity and pharynx.

METHODS.
The Massachusetts General Hospital Tumor Registry was queried for all patients with ICD-O-3 codes corresponding to both CLL/SLL and HNC from January 1989 to July 2010, returning seventeen patients. The data collected included patient demographics, blood work and cytogenetics (when available) at the time of CLL diagnosis, primary HNC tumor histology and stage, and all pertinent treatment data, including types of treatment and clinical response. Survival was calculated using the Kaplan-Meier method.

RESULTS.
Seventeen patients had a diagnosis of both CLL and HNC. Of those, three were excluded from the study as treatment data was unavailable. The fourteen remaining included 12 males and 2 females. Eight patients had their CLL diagnosed first, and had a median interval to HNC diagnosis of 80 months (2-210 months; mean 89 months), four had their HNC diagnosed first and had a median interval to CLL of 1 month (1-100 months; mean 26 months), and two patients had concurrent diagnoses. The median age at diagnosis was 58.5 years (CLL) and 64 years (HNC). Nine patients (64%) were former or current smokers, all with at least a 20 pack year smoking history. Seven patients presented with Rai stage 0 CLL, three patients with Rai stage 1, one patient each with Rai stage 2 and 3, and two with unknown presentations. HNC tumor presentations included 3 T1 tumors, 3 T2 tumors, 3 T3 tumors, 2 T4 tumors, and 3 TX tumors. Three patients had HPV assessed in their tumor and all were positive.
Out of the fourteen patients, nine (64%) received first-line chemotherapy for their CLL: 4 with chlorambucil, 1 with fludarabine/rituximab (FR), 1 with FR/lenalidomide, 1 with rituximab, and 1 each with cytoxan/vincristine and steroid monotherapy. Eight patients received second line therapy, three received third line therapy and one received 7 lines of therapy. Six patients (43%) received chemotherapy and radiation as their primary treatment for their Head and Neck tumor, three (21%) received surgery and radiation, three (21%) received only radiation, one received surgery, and one received radiation, chemotherapy, and surgery. One patient required hospitalization due to neutropenic fever during their radiation treatment, and one patient had a week of chemotherapy withheld due to leukopenia, but both were able to complete their full course of therapy. Three patients (21%) received chemotherapy for their CLL before any HNC treatment. These three patients were able to tolerate full HNC therapy without infectious complications or unanticipated cytopenias.
First-line therapy for HNC had a median progression-free survival of 26.9 months (range 10.7 – 145.2 months; 95% CI, 12 to 42 months) and a median overall survival of 45.1 months (range 1 to 256.1 months; 95% CI, 9 to 81 months). The median overall survival from HNC for treated CLL patients was 22.6 months and for untreated 59.2 months (p= 0.596). Five patients died from their HNC (36%), two patients died from their CLL (14%), two patients died from unrelated causes, and five patients remain in remission. There were no significant differences in HNC presentation or survival between treated and untreated CLL.

CONCLUSIONS.
Prior or concurrent CLL therapy did not affect HNC treatment or induce any unexpected toxicities. Interestingly, seven out of fourteen patients (including 2 out of 3 HPV positive) were diagnosed with HNC within 6 months of CLL diagnosis, suggesting that the risk of secondary malignancies may be independent of the degree of immunosuppression attributable to progressive CLL or its therapy. This hypothesis should be explored in a larger population.

Disclosures:
No relevant conflicts of interest to declare.