De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience

Abstract

To determine the clinical fate of patients with de novo deletion 17p13.1 (17p-) chronic lymphocytic leukemia (CLL), we retrospectively studied the outcome of 99 treatment-naive 17p- CLL patients from the M. D. Anderson Cancer Center (n = 64) and the Mayo Clinic (n = 35). Among 67 asymptomatic patients followed for progression, 53% developed CLL requiring treatment over 3 years. Patients who had not progressed by 18 months subsequently had stable disease, with 3 of 19 patients progressing after follow-up of up to 70 months. Risk factors for progressive disease were Rai stage of 1 or higher and unmutated immunoglobulin variable region heavy chain (IgVH). The overall survival rate was 65% at 3 years. Rai stage 1 or higher, unmutated IgVH, and 17p- in 25% or more of nuclei were adverse factors for survival. The 3-year survival rates of patients with 1 or fewer, 2, and 3 of these factors were 95%, 74%, and 22%, respectively (P < .001). Response rates to therapy with rituximab (n = 6); purine analogues and rituximab (n = 25); and purine analogues, rituximab, and alemtuzumab (n = 16) combinations were 50%, 72%, and 81%, respectively. Patients with 17p- CLL exhibit clinical heterogeneity, with some patients experiencing an indolent course. Survival can be predicted using clinical and biologic characteristics.

Figure 1

Progression to therapy requirement for asymptomatic patients after diagnosis of 17p− CLL. (A) The 3 year progression rate to therapy requirement was 53% for the study cohort. (B) Progression to therapy requirement by institution. The 3-year progression rate to therapy requirement was 56% for patients from MDACC and 47% for patients from the Mayo Clinic (P = .17). (C) Progression to therapy requirement, effect of clone size. Patients with 75% or more nuclei with 17p− were at increased risk of progression (79% at 3 years vs 40% for the remaining patients, P = .001). (D) Model for progression to first therapy. Risk factors were Rai stage 1 or higher, and unmutated IgV_H gene. Patients with 0, 1, and 2 risk factors had 3-year progression rates of 0%, 54%, and 100%, respectively (P < .001). Thirteen patients were not assessable due to missing data on IgV_H status.

Figure 2

Survival after 17p− CLL diagnosis. (A) The rate of survival 3 years from the date of FISH diagnosis was 65%. (B) Survival after 17p− CLL diagnosis by institution. The rate of survival 3 years from the date of FISH diagnosis was 71% for patients from MDACC and 56% for patients from the Mayo Clinic (P = .43). (C) Survival after 17p− CLL diagnosis, effect of clone size. Survival was most favorable in patients with less than 25% deleted nuclei (3-year survival rate, 92%), intermediate in patients with 25% to 74% deleted nuclei (3-year survival rate, 67%), and least favorable in patients with 75% or more deleted nuclei (3-year survival rate, 40%; P = .001). (D) Model for survival after 17p− CLL diagnosis. Risk factors were Rai stage 1 or higher, unmutated IgV_H gene, and 17p loss in ≥ 25% of nuclei. Patients with 1 or fewer, 2, and 3 risk factors had 3-year survival rates of 95%, 74%, and 22%, respectively (P < .001). Sixteen patients were not assessable due to missing data on IgVH status.

Figure 3

Time to progression (TTP) after first therapy. (A) Patients with a complete response (CR), unconfirmed CR, or nodular partial response (Nod PR) experienced a significantly better TTP (51% at 3 years) than patients with a partial response (median TTP 14 months, P = .001 vs CR/Nod PR). Three patients with a partial response were not assessable due to inadequate follow-up of disease status. (B) Survival after first therapy. Patients with a complete response (CR), unconfirmed CR, or nodular partial response (Nod PR) experienced significantly better survival (86% at 3 years) than patients with a partial response (median survival 28 months, P = .05 vs CR/Nod PR) or patients with no response to treatment (median survival 20 months; P = .001 vs CR/Nod PR; P = .13 vs partial response).