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E.D. McPhail et al.
Of note, progression or relapse occurred almost exclu- sively within 12 months of diagnosis, suggesting that EFS12 is worth further evaluation as an endpoint for stud- ies of DH/THL.39
Treatment with R-CODOX-M/IVAC may result in superior outcomes for patients younger than 60 years, despite the preponderance of aggressive (high-grade) his- tological findings within this group. However, selection bias may also have an important role in the superior out- comes for this cohort. A multicenter retrospective analy- sis evaluated effect of induction regimen and stem cell transplantation on outcomes in DHL, showing that inten- sive induction therapy was not associated with improved OS.13 In a meta-analysis of 11 studies and 394 patients, OS was not different across the treatment approaches used in our series.40 Sun et al. reported a 2-year progres-
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sion-free survival rate of 60% and a 2-year OS rate of 82% for 16 patients treated with R-CODOX-M/IVAC followed by hematopoietic stem cell transplantation.30 No randomized clinical trial for this histological subset is cur- rently available.
Second, DH/THL patients with high-grade histological characteristics showed a tendency, although not statisti- cally significant, toward a more aggressive clinical course. Published literature has provided mixed results on this issue. Johnson et al., in their retrospective study of BCLU and DLBCL with concurrent MYC and BCL2 rearrange- ments identified through karyotypic analysis, showed that BCLU morphological appearance was associated with poorer outcome (P<0.001).6 Other investigators have obtained similar results.40-42 Blastoid morphological char- acteristics have also been associated with adverse clinical
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Figure 3. Event-free survival and overall survival of patients receiv- ing anthracycline-based therapy. (A) Event-free survival of the 70 patients receiving anthracycline- based therapy at the time of diag- nosis of double-hit/triple-hit lym- phoma. (B) Overall survival of the 70 patients.
Figure 4. Overall survival according to transformation of previously diagnosed low-grade lymphoma, morphological characteristics, BCL2 rearrangement status, and MYC partner (IG gene versus non-IG gene). (A) Patients with double- hit/triple-hit lymphoma (DH/THL) at transformation of previously diag- nosed low-grade lymphoma had inferior overall survival (OS) com- pared with patients who had de novo DH/THL [hazard ratio (HR) 2.99, P=0.007)]. (B) DH/THL patients with high-grade morpholog- ical characteristics showed a ten- dency toward inferior OS compared with patients with large-cell mor- phological characteristics, but it was not statistically significant (HR 2.32, P=0.09). (C) DH/THL patients with BCL2 rearrangements [MYC/BCL2, MYC/BCL2/BCL6, and MYC/BCL2 (BCL6 unknown)], so- called DH-BCL2/TH, showed a non- significant tendency toward inferior OS compared with those who did not have BCL2 rearrangements (MYC/BCL6) (HR 2.44, P=0.16). (D) No association was observed between MYC partner (IG versus non-IG) and OS (P=0.99).
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haematologica | 2018; 103(11)