Association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer

Abstract

Background: Severe treatment-related lymphopenia occurs commonly in many cancers and is associated with early tumor progression. Data are lacking as to whether this occurs in squamous cell head and neck cancer.

Methods: Serial total lymphocyte counts were retrospectively reviewed in patients with newly diagnosed squamous head and neck cancer undergoing chemoradiation and associated with treatment outcomes.

Results: The median baseline total lymphocyte count in 56 patients was 1660 cells/mm(3) , which fell by 73% to 445 cells/mm(3) 2 months after initiating chemoradiation (p < .0001). Human papillomavirus negative (HPV-) patients with a total lymphocyte count <500 cells/mm(3) at 2 months had significantly earlier disease progression than those with higher total lymphocyte counts (hazard ratio [HR], 5.75; p = .045).

Conclusion: Baseline total lymphocyte counts were normal, but at 2 months approximately 60% of patients had severe treatment-related lymphopenia regardless of HPV status. Severe treatment-related lymphopenia in HPV- patients is independently associated with earlier disease progression. Prospective studies are needed to confirm these findings, which suggest that immune preservation is important in this cancer.

Keywords: chemotherapy; head and neck squamous cell carcinoma; lymphopenia; radiation; treatment-related toxicities.

Figure 1

Treatment-related lymphopenia is common and severe in newly diagnosed HNSCC. Median total lymphocyte counts (TLCs) over 12-month period after initiation of chemo/RT were analyzed (n=56). TLCs were normal prior to chemo/RT. However, 2 months after initiation of concurrent chemo/RT, TLCs fell rapidly by 73% with 61% patients having TLC <500 cells/mm3. TLCs remained below 1000 cells/mm3 throughout the observation period. Gray arrow depicts the start of radiation exposure and chemotherapy. Abbreviations: TLC, total lymphocyte count; RT, radiation.

Figure 2

Treatment-related lymphopenia is seen in both HPV+ and HPV− patients. Median total lymphocyte counts dropped significantly with the chemo/RT in both HPV+ and HPV− patients. (A) HPV+ patients (n=34) had baseline median TLC of 1610 cells/mm3 which fell to 320 cells/mm3 2 months after beginning chemo/RT. A total of 26 patients (76%) had TLC <500 cells/mm3 at 2 months. (B) HPV− (n=22) patients started with a median TLC at 1770 cells/mm3 which fell to 550 cells/mm3 with 8 patients (36%) having TLC <500 cells/mm3 2 months after beginning chemo/RT. Abbreviations: TLC, total lymphocyte count; RT, radiation; HPV, Human papillomavirus.

Figure 3

Severe treatment-related lymphopenia in HPV− patients is associated with early tumor recurrence. (A) Kaplan-Meier survival curves for patients with HPV positive patients (above red line) and HPV negative patients (below green line). The median overall survival in HPV+ patients is significantly longer compared to HPV− patients (p=0.006). (B) The progression-free survival in HPV+ patients is also significantly longer compared to HPV− patients (p=0.01). (C) HPV− patients who developed severe treatment-related lymphopenia (TLC<500 cells/mm3) 2 months after beginning chemo/RT had a strikingly higher hazard rate for disease progression than those whose TLC remained higher (multivariate analysis HR 5.75, 95%CI: 1–32; p=0.045). Abbreviations: TLC, total lymphocyte count; RT, radiation; HPV, Human papillomavirus.