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NPM-ALK quantification by RQ-PCR and dPCR in ALCL
Discussion
In our previous study, quantitative measurement of NPM-ALK fusion gene transcripts in blood or BM using a cut-off of 10 NCN in the RQ-PCR analysis allowed us to identify the group of patients with the highest risk of relapse. We were able to confirm these results in the vali- dation cohort of uniformly treated NPM-ALK-positive ALCL patients. As in our previous analysis, only 20% of patients had more than 10 NCN NPM-ALK detectable in BM. Two-thirds of those patients relapsed in both series of altogether 175 ALCL patients.
When comparing the event-free survival of the very high-risk group determined by quantification of MDD in blood between the two cohorts, the EFS of high-risk patients was somewhat higher in the validation cohort than in the earlier cohort. This difference might be attrib- utable to a selection bias with a higher event-free survival in the current cohort analyzed in blood compared to the previously reported cohort (previous cohort 61±6%, cur- rent cohort 74±5%). In the current validation cohort,
A
MDD results measured in blood and BM of the same patients were comparable and had the same prognostic impact. For future studies, investigation of peripheral blood could therefore be sufficient for quantitative MDD evaluation. This is especially helpful bearing in mind the application of MRD to follow the course of disease in very high-risk patients or after relapse.
Compared to the earlier cohort including patients diag- nosed until 2005, the survival of the very high-risk patients, as defined by more than 10 NCN in BM, improved in the validation cohort (83% compared to 46%). New therapeutic options became available for patients with relapsed ALCL, ranging from vinblastine monotherapy, brentuximab vedotin, ALK kinase inhibitors to PD-L1 checkpoint inhibitors.15,17,22-28 In addi- tion, allogeneic blood stem cell transplantation was increasingly used for consolidation in relapse.29-32
Our results show that separation of patients with a high risk of relapse can be achieved by quantification of MDD in patients with ALCL with the prerequisites that quanti- tative PCR evaluation is performed in the same laboratory
B
Figure 2. Outcome according to NPM- ALK copy numbers measured by quanti- tative real-time polymerase chain reac- tion in blood and bone marrow. Cumulative incidence of relapse (according to a cut-off of 10 normalized copy numbers of NPM/ALK/104 copy numbers of ABL1) measured in initial (A) blood and (B) bone marrow samples in 70 patients. PB: blood; BM: bone mar- row; NCN: normalized copy number.
haematologica | 2020; 105(8)
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