Minimal residual disease level determined by flow cytometry provides reliable risk stratification in adults with T‐cell acute lymphoblastic leukaemia

Abstract

Summary Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B‐cell ALL, reports of adult T‐cell ALL (T‐ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)‐based MRD at the end of induction (EOI‐MRD). The present retrospective study included 94 adult patients with T‐ALL. MRD was detected by six‐ to eight‐colour FCM. Patients who were EOI‐MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse‐free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI‐MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo‐HSCT) at their first remission, EOI‐MRD positivity was predictive of post‐transplant relapse (2‐year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI‐MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI‐MRD based on FCM was an independent prognostic factor for relapse and survival in adult T‐ALL. For patients who underwent HSCT, EOI‐MRD could be used to identify patients with a high risk of relapse after allo‐HSCT.

Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

“…In detail, T-ALL backbone panels are set up to evaluate both the asynchronous expression of classic T-cell maturation markers (namely, membrane/cytoplasmic CD3, CD5, CD7, CD2, CD4, CD8, CD34, CD45) and the ectopic expression of thymic antigens (such as CD99 and CD1a), as well as TdT, CD10, CD38 and CD56 [ 50 , 62 , 63 ]. Recently, several works have consistently confirmed that MFC-MRD assay (performed early after induction therapy, by using 6–8 color panels with a threshold of 0.01%) well represents a consistent prognostic factor, both in adults and in children with T-ALL [ 64 , 65 , 66 ]. Further studies are needed to elucidate whether patients with early undetectable MFC-MRD can be eligible for reduced intensity therapy [ 67 ], and whether novel NGF approaches can actually improve MRD detection and clinical management in T-ALL patients [ 68 ].…”

Immunophenotypic measurable residual disease monitoring in adult acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation

“…Concerning T-ALL, a multicenter study regarding 274 pediatric and adult patients showed that a negative MFC MRD assessment (6 color panel, sensitivity 6 x 10 -5 ), on day 15 might be useful for an early and accurate identification of patients with a very low risk of relapse (32). Similarly, a retrospective study on 94 adult patients affected by T-ALL showed that MFC MRD (6-8 color, sensitivity 10 -4 ) positivity at the end of induction was an independent prognostic factor for cumulative incidence risk, relapse-free survival, and OS (33).…”

“…In keeping with these premises, in young adult and adult patients allo-HSCT is currently part of postconsolidative therapy in case of high-risk features such as Phpositivity, Ph-like disease, and persistent MRD as assessed by either MFC or RQ-PCR (11,12). In MRD regard, prospective and retrospective multicenter studies have demonstrated that allo-HSCT improves the outcome of adult ALL patients who are MRD positive after induction (33,40) or consolidation therapy (41,42).…”

“…A few studies have specifically analyzed the role of MFC MRD monitoring in ALL prior to and following allo-HSCT. As shown in Table 1 (33,(47)(48)(49)(50)(51)(52)(53)(54)(55), data related to adult patients mostly derive from retrospective and heterogeneous series, sometimes including children, and using different sensitivity levels [10 -3 to 10 -5 ].…”

The Role of Proteasome Inhibitors in Treating Acute Lymphoblastic Leukaemia

“…However, more studies are needed to evaluate this strategy in treating relapse/refractory disease in adult. The findings of high MRD negativity rate when combining proteasome inhibitors with chemotherapy in treating newly diagnosed ALL in adult is a promising finding, since MRD is crucial determinant of prognosis in adult ALL ( 74 – 76 ). This therapeutic strategy for newly diagnosed ALL can potentially improve outcome of ALL, particularly in adult patients.…”