Precursor B-acute lymphoblastic leukemia occurring in patients with a history of prior malignancies: is it therapy-related?
BACKGROUND
Precursor B-acute lymphoblastic leukemia occurring in patients with a history of malignancies is uncommon, and this condition is not well understood.


METHODS
A retrospective review of 457 adults with precursor B-acute lymphoblastic leukemia treated at our hospital identified 44 (9.6%) patients with prior malignancies. The clinical and genetic characteristics of this group of patients was compared with those of their counterparts with de novo disease and the relationship with prior chemoradiation therapy was assessed.


RESULTS
Thirty of 44(6.2%) patients received cytotoxic therapies, whereas 14 patients did not. The former group showed a significantly shorter interval from prior malignancy to onset of precursor B-acute lymphoblastic leukemia (36 versus 144 months; P = 0.002). Compared with 413 de novo cases, the frequencies of t(4;11)(q21;q23) (P<0.001) and hypodiploidy (P = 0.009) with loss of chromosome 5, 7 or 17 were significantly higher in patients who received topoisomerase II inhibitor and/or alkylating agents. By contrast, Philadelphia-positive and normal karyotype were more frequent in patients who either did not receive chemotherapy or received only local radiation or nucleoside analogs. Patients with precursor B-acute lymphoblastic leukemia following prior malignancies and chemoradiation were older, had a lower complete remission rate and showed an inferior survival in univariate, but not multivariate analysis.


CONCLUSIONS
The data support the interpretation that therapy-related precursor B-acute lymphoblastic leukemia does occur. In particular, cases associated with t(4;11)(q21;q23) or hypodiploidy with -5, -7, -17 are likely to be therapy-related and have a poor prognosis. The inferior outcome of these patients may be attributable to the high-risk cytogenetic abnormalities that are found in this group of patients.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guilin
G
Tang
Zhuang
Z
Zuo
Deborah A
DA
Thomas
Pei
P
Lin
Dingsheng
D
Liu
Ying
Y
Hu
Hagop M
HM
Kantarjian
Carlos
C
Bueso-Ramos
L Jeffrey
LJ
Medeiros
Sa A
SA
Wang
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D002869:Chromosome Aberrations / Q000187:drug effects*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000532:radiotherapy; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D059005:Topoisomerase II Inhibitors