Clinical significance of newly emerged isolated del(20q) in patients following cytotoxic therapies

Abstract

Deletion 20q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(20q) in patients following cytotoxic therapies raises concerns for an emerging therapy-related myeloid neoplasm. In this study, we identified 92 patients who acquired isolated del(20q) in their bone marrow following cytotoxic therapies for malignant neoplasms. Seventy-six patients showed interstitial and sixteen patients showed terminal 20q deletion. The median interval from prior cytotoxic therapies to detection of del(20q) was 58 months (range, 5-213 months). With a median follow-up of 23 months (range, 1-183 months), 21 (23%) patients developed therapy-related myeloid neoplasm and 71 (77%) patients did not. In patients who developed therapy-related myeloid neoplasm, del(20q) presented in a higher percentage of metaphases (60 vs 25%, Po 0.0001); persisted for a longer period of time (24 vs 10 months, P = 0.0487); and was more often a terminal deletion (33 vs 13%, P = 0.0006) compared with patients who did not develop therapy-related myeloid neoplasm. Clonal evolution was only detected in patients with therapy-related myeloid neoplasm (4 patients, 19%). We conclude that del(20q) emerging after cytotoxic therapy represents an innocuous finding in more than two-thirds of patients. In patients who develop a therapy-related myeloid neoplasm, del(20q) often involves a higher percentage of metaphases, persists longer and more frequently is a terminal rather than an interstitial deletion.

Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of BIRC3 gene: a case report

“…This includes a case of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia [15] and two cases of marginal zone lymphoma [12, 16]. Another study of 64 patients with chronic lymphocytic leukemia (CLL) revealed that del(20q) appears to be a therapy-related abnormality in CLL involving both myeloid and lymphoid cells and may represent disease progression [17, 18]. Given that del(20q12) in this patient was identified in the lymph node and not skin lesion and that the patient has not received any prior chemotherapy at that time, this abnormality is likely related to transformation of MZL to DLBCL and implicates a loss of important gene(s) likely with tumor suppressor function.…”

How I investigate Clonal cytogenetic abnormalities of undetermined significance

“…In contrast, 11 of 12 patients with transient del(7q) did not show BM disease during the follow‐up interval, and the exception was a patient in whom del(7q) was no longer detectable, but who subsequently acquired an unrelated CCA and was diagnosed with t‐MDS . In the study of del(20q) as a sole abnormality following cytotoxic therapies, del(20q) was persistently or intermittently detected in 46 patients and transient in 15 patients. Of the former, 15 of 46 (33%) patients developed t‐MDS/AML; in contrast, of the 15 patients with transient del(20q), only 2 (13%) patients developed t‐MDS/AML later during the follow‐up, and both patients had newly emerged unrelated CCA.…”

“…In a study that included 92 patients who acquired del(20q) after cytotoxic therapies, 21 (23%) patients had t‐MDS/AML and 71 (77%) did not. Del(20q) was present in a significantly higher percentage of metaphases in patients with t‐MDS/AML comparing to patients without (60% vs 25%, P < .0001) . In another study of 21 patients who acquired isolated del(5q) following cytotoxic therapies, all 12 patients with a large del(5q) clone (45%‐100% metaphases) developed t‐MDS/AML vs none of 9 patients with a small del(5q) clone .…”

“…To date, most CCAUS reported have been single isolated abnormalities, including a chromosomal gain such as +8, +Y, +15; or a partial loss of a chromosome like del(20q), del(5q), del(7q), del(11q); or balanced rearrangements including t(11q23;v), t(1;16)(p37;q21), inv(5)(p15.1q11.2), t(5;19)(p15.3;q11.1), t(1;10)(q12;q26.2), and t(9;17)(q34;q21) . None of the CCAUS falls into the poor‐ or very poor‐risk IPSS groups .…”

“…Del(20q) as a sole abnormality is uncommon in t‐MDS/AML . In a study that included 92 patients who acquired del(20q) as the sole abnormality after cytotoxic therapy, only 21 (23%) patients had a diagnosis of t‐MDS/AML, 46 had no evidence of t‐MDS/AML, and 25 had an inconclusive BM diagnosis with a median follow‐up of 23 months …”