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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.

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 lymphoblastic 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 chromosomes 5/7 aberrations (P=0.02). Although therapy-related acute lymphoblastic 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 survival 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 hematopoietic cell transplantation. In conclusion, therapy-related acute lymphoblastic 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 neoplasms. 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.

SUBMITTER: Aldoss I

PROVIDER: S-EPMC6165794 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to <i>de novo</i> acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients.

Aldoss Ibrahim I Stiller Tracey T Tsai Ni-Chun NC Song Joo Y JY Cao Thai T Bandara N Achini NA Salhotra Amandeep A Khaled Samer S Aribi Ahmed A Al Malki Monzr M MM Mei Matthew M Ali Haris H Spielberger Ricardo R O'Donnell Margaret M Snyder David D Slavin Thomas T Nakamura Ryotaro R Stein Anthony S AS Forman Stephen J SJ Marcucci Guido G Pullarkat Vinod V

Haematologica 20180614 10

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 lymphoblastic leukemia, 93 (9.1%) were clas ...[more]

PMID: 29903756

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Project description:Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers.There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results.Patients-We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis-Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations-Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835) using polymerase chain reaction methods.Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22), t(12;21), and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7%) and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22), MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group (P = .031).The event-free survival was also found to be worse (P = .040).Our data are in accordance with those published previously, confirming the overall frequency of cytogenetic abnormalities and their prognostic relevance.

Dataset Information

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.

Publications

Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to <i>de novo</i> acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients.

Similar Datasets

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