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I. Aldoss et al.
diagnosed over a 15 years period which introduces bias both with regard to changing treatments for the primary malignancies as well as ALL therapy. Examples include decreasing use of anthracyclines for breast cancer therapy as well as improved outcome of HCT over the time period of the study. It is also possible that some cases of t-ALL may be a coincidental occurrence of ALL after the patient has had a previous malignancy particularly in cases with long latency and lacking MLL rearrangement or mono- somy karyotype. Moreover, the referral bias to our center may have introduced overestimation of t-ALL frequency. This is likely because t-ALL cases may have been per- ceived as being high risk, leading to earlier referral as well as earlier application of more intense therapy including allogeneic HCT. Our data suggest a good outcome for t-ALL when allogeneic HCT is used in CR1 and these patients should be considered candidates for HCT if they are in sustained remission from their primary malignancy. What remains unclear is the outcome of these cases, par- ticularly ones treated with an intensive pediatric type ALL regimen in younger patients. The use of such regimens could be problematic in some of these patients due to
cumulative toxicity from treatment of their previous malignancy. This high rate of allogeneic HCT use for both de novo and t-ALL in our cohort may have minimized the survival difference between the two groups and underes- timate the poor prognosis of t-ALL.
In conclusion, we have attempted to define t-ALL more narrowly using stricter criteria than those used by previous reports and show that these cases have cytoge- netic abnormalities that confirm a causative role for their prior cytotoxic therapy in many cases. Large molecular studies using next generation sequencing methodology and accurate correlation with clinical data regarding prior cytotoxic therapy will be required to further characterize this entity.
Funding
Research reported in this publication included work performed in the Biostatistics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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