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An important feature of studies and treatment paradigms for B‑cell ALL is the impact of MRD. MRD is the low level presence of lymphoblasts following initial therapy that are not detected using traditional methods such as microscopy. MRD can be detected by a variety of sensitive methods, including flow cytometry for leukemia‑associated immunophenotypes, as well as by FISH or PCR testing for leukemia‑specific fusion transcripts or gene rearrangements.
Low‑level molecular disease in patients with ALL can be detected following induction or consolidation before transplant, and has been associated with worse survival and poor prognosis, compared with those without evidence of MRD.
Patients with newly diagnosed B‑cell ALL receive intensive treatments with the aim of suppressing their lymphoid blast population to a certain level. If that level is below molecular detection, as measured by sensitive MRD techniques, then the likelihood that their disease will reemerge in the future is significantly lower. If the suppression of lymphoid blasts is not sufficient and lymphoid blasts are still detected by MRD testing, then their disease is more likely to relapse subsequently.
A variety of methods for MRD quantification are available, including flow cytometry, PCR testing, and next-generation sequencing that can increase the sensitivity offered in certain settings. Regardless of which method is used, MRD status is increasingly important to establish risk of relapse in patients receiving standard therapies for B‑cell ALL.
A common approach to the treatment of B‑cell ALL, particularly for those with high-risk disease, is to suppress the lymphoid blast population, achieve a state of deep molecular remission with induction and/or consolidation therapy, and thereafter, increase the chance of cure with a consolidative SCT. A study in which 43 patients with high-risk ALL who received SCT found that individuals with evidence of MRD had worse survival outcomes vs those with no evidence of MRD.