Clinical Implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32) and -17p13 (p53) Deletions in Myeloma Patients Treated with High Dose Therapy.
Authors: Gertz Morie Abraham , Lacy Martha Q. , Dispenzieri Angela , Greipp Philip R. , Litzow Mark R. , Henderson Kim J. , Van Wier Scott A. , Ahmann Gregory J. , Fonseca Rafael 
Published: October 2019

Introduction: FISH is able to recognize chromosomal deletions and translocations with a greater sensitivity than conventional cytogenetics. Specific abnormalities have been associated with prognosis. Initial observations suggest a poor outcome for patients with -17p13.1, chromosome 13 abnormalities (Δ13) and t(4;14)(p16.3;q32). In contrast a good outcome has been shown in some series for patients with t(11;14)(q13;q32). We analyzed the value of FISH in patients receiving high dose therapy .

Patients and Methods: We studied by cIg-FISH 226 patients undergoing high dose therapy at Mayo Clinic between 1/1990 and 9/2001. All patients had a pretransplant cIg-FISH done on cytospin slides from marrow aspirates for t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13.1(p53). Information was available regarding Δ13 for all patients (+ in 52%).

Results:

The prevalence of the abnormalities were: t(11;14)(q13;q32) 17% (n=197), t(4;14)(p16.3;q32) 13% (n=153), and -17p13.1 11% (n=168). The overall survival (OS)was significantly shortened in patients with t(4;14)(p16.3;q32) (18.2 vs. 43.3 mo, p=0.001) (figure) and patients with -17p13.1 (14.7 vs. 38.6 mo, p=.01). OS was not different for patients with the t(11;14)(q13;q32) (36.2 vs. 34.8 mo, p=ns). Likewise time to progression (TTP) was shortened in patients with t(4;14)(p16.3;q32) (8.5 vs 17.7 mo, p=.001) and -17p13.1 (8.3 vs. 16.2 mo, p=0.005). TTP was also not affected significantly by the t(11;14)(q13;q32) (20.7 vs. 14.9 mo, p=NS). To dissect the specific contribution of t(4;14)(p16.3;q32) we did a subset analysis of patients who also had Δ13, since 85% of patients with t(4;14)(p16.3;q32) are expected to have Δ13. Of 84 studied for both abnormalities 22 had both Δ13 and t(4;14)(p16.3;q32). The OS was significantly shorter in patients with both abnormalities versus those with Δ13 alone (26.6 vs. 18.2 months, p=0.001). When a multivariable analysis of the impact of Δ13 and t(4;14)(p16.3;q32) were placed into a Cox model the hazard function for t(4;14)(p16.3;q32) was greater than Δ13 (2.6 versus 1.6). Δ13 had only borderline significance in this model (p=0.06).

Conclusion: We have been unable to corroborate the improved outcome after transplant for patients with t(11;14)(q13;q32). As has been reported in patients with conventional and high dose therapy -17p13(p53) and t(4;14)(p16.3;q32) have clinical importance for estimation of OS and TTP. In this patient group the t(4;14)(p16.3;q32) carried a greater adverse impact than did Δ13, and identifies a subset of patients whose time to progression is 8.5 months. These patients likely do not benefit from autologous transplant and are candidates for novel therapeutic approaches.

Outcome

Successful determination Patients with translocation or deletion Survival (months) with/without abnormality Time to Progression (months) with/without abnormality * p<0.01;**p<0.001 t(11;14)(q13;q32) 197 34(17%) 36.2/34.8 20.7/14.9 p53 168 18(11%) 14.7/38.6 * 8.3/16.2 * t(4;14)(p16.3;q32) 153 26(17%) 18.2/43.3 **figure 8.5/17.7 ** t(4;14)(p16.3;q32)/Δ13+ patients 84 22(26%) 18.2/26.6 8.2/12.8 *

Figure Figure