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Ferrata Storti Foundation
Acute Lymphoblastic Leukemia
Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable
in transplanted patients
Haematologica 2018 Volume 103(10):1662-1668
Ibrahim Aldoss,1 Tracey Stiller,2 Ni-Chun Tsai,2 Joo Y. Song,3 Thai Cao,1,4 N. Achini Bandara,1 Amandeep Salhotra,1 Samer Khaled,1 Ahmed Aribi,1 Monzr M. Al Malki,1 Matthew Mei,1 Haris Ali,1 Ricardo Spielberger,1,4
1151 Margaret O’Donnell, David Snyder, Thomas Slavin, Ryotaro Nakamura,
Anthony S. Stein,1 Stephen J. Forman,1 Guido Marcucci1 and Vinod Pullarkat1
1Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte; 2Department of Information Sciences, Division of Biostatistics, City of Hope, Duarte; 3Department of Pathology, City of Hope, Duarte; 4Kaiser Permanente, Department of BMT, Southern California Medical Group, Los Angeles and 5Department of Medical Oncology, Division of Clinical Genetics, City of Hope, Duarte, CA, USA
ABSTRACT
Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lym- phoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the MLL gene rearrangement compared to those with other cytogenetics. When compared to de novo acute lymphoblastic leukemia, therapy-related patients were older (P<0.01), more often female (P<0.01), and had more MLL gene rearrangement (P<0.0001) and chro- mosomes 5/7 aberrations (P=0.02). Although therapy-related acute lym- phoblastic leukemia was associated with inferior 2-year overall survival compared to de novo cases (46.0% vs. 68.1%, P=0.001), prior exposure to cytotoxic therapy (therapy-related) did not independently impact sur- vival in multivariate analysis (HR=1.32; 95% CI: 0.97-1.80, P=0.08). There was no survival difference (2-year = 53.4% vs. 58.9%, P=0.68) between the two groups in patients who received allogenic hematopoi- etic cell transplantation. In conclusion, therapy-related acute lym- phoblastic leukemia represents a significant proportion of adult acute lymphoblastic leukemia diagnoses, and a subset of cases carry clinical and cytogenetic abnormalities similar to therapy-related myeloid neo- plasms. Although survival of therapy-related acute lymphoblastic leukemia was inferior to de novo cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities.
Introduction
Therapy-related leukemia has increasingly emerged as a long-term complication of cytotoxic therapy (i.e., chemotherapy and radiation) for patients who have undergone treatment for preceding malignancies.1 Therapy-related myeloid neo- plasms (t-MNs) are widely recognized and comprise an established category in the WHO classification of MNs, which include therapy-related acute myeloid
Correspondence:
ialdoss@coh.org
Received: March 19, 2018. Accepted: June 8, 2018. Pre-published: June 14, 2018.
doi:10.3324/haematol.2018.193599
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/10/1662
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