B-Lymphoblastic Leukemia/Lymphoma Occurring in Patients with a History of Malignancy: Is It Therapy-Related?
Guilin Tang, Zhuang Zuo, Yin Hu, Pei Lin, Jeffrey L Medeiros, Sa A Wang. UT MD Anderson Cancer Center, Houston, TX
Background: B-lymphoblastic leukemia/lymphoma (B-LBL) occurring in patients with a history of other malignancy is rare; it remains unclear if B-LBL arising in this clinical context is the result of prior cytotoxic therapy; and how these neoplasms differ from the de novo counterpart.
Design: We retrospectively reviewed 457 adult patients with B-LBL treated at our hospital in the past 6-7 years and identified 44 (9.1%) patients with various prior malignancies. We focused this study on clinical and genetic characteristics of B-LBL in relation to prior cytotoxic therapies.
Results: Thirty (6.2%) of these 44 patients received cytotoxic therapies, whereas 14 patients did not. The former group showed a significant shorter interval from prior malignancy to onset of B-LBL [36 (6-216) versus 144 (7-420) months; p=0.002]. Compared to 413 patients without prior malignancies: the frequencies of t(4;11)(q21;q23), hypodiploidy and loss of 5, 5q, 7, 7q and 17 were significantly higher, and related to prior therapy with toposomerase II inhibitor and/or alkylating agents; whereas the Philadelphia chromosome and a normal karyotype showed a frequency similar to their de novo counterpart and occurred in patients either received none or less leukemogenic agents. Patients with B-LBL following other malignancies were older, less often qualified for stem cell transplant, and showed an inferior overall survival in univariate, but not multivariate analysis.
Conclusions: In patients with a history of other malignancies, B-LBL with t(4;11)(q21;q23), hypodiploidy and particularly with loss of chromosomes 5, 7, or 17 are likely linked to prior cytotoxic therapy. Other B-LBL cases in this clinical context might be coincidental or reflect individual genetic susceptibility to cancer. The inferior outcome we observed may be attributable to older age and/or high-risk cytogenetics as a result of prior cytotoxic therapy.
|De novo (n=413)||History of prior malignancies||p|
|No prior cytotoxic therapy (n=14)||With prior cytotoxic therapy (n=30)|
|Age (years)||40 (18-83)||68 (39-86)||64 (30-86)||P<0.001|
|Normal karyotype||93 (22.5%)||2 (14%)||7 (23%)||0.483|
|t(4;11)(q21;q23)||18 (4.3%)||1 (7%)||7 (23%)||<0.001|
|t(9;22)(q34;q11.2)||128 (31%)||9 (64%)||7 (23%)||0.102|
|Hyerpdiploidy||22 (5.3%)||0||1 (3.3%)||0.125|
|Hypodiploidy||19 (4.6%)||1 (7%)||6 (20%)||0.009|
|-5, -7, -5q, -7q, -17||32 (7.7%)||1 (7%)||7 (23%)||0.009|