Importance of measurable residual disease in the outcome of adults with acute lymphoblastic leukemia after allogeneic stem cell transplantation: Long follow-up analysis from a single transplant center

Abstract

Introduction: In this retrospective study, with prolonged follow-up, we analyze the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult acute lymphoblastic leukemia (ALL) and the impact of pre-transplantation measurable residual disease (pre-HSCT MRD).

Methods: Detection of MRD was performed by multiparametric flow cytometry (MFC) for Philadelphia chromosome-negative ALL (Ph-neg ALL) and by classic genetic tests for Ph-pos ALL.

Results: Among 46 patients in first complete remission (CR1) who had available MRD data, 1- and 3-year cumulative incidences of relapse (CIR) for patients with positive and negative MRD were 47.1% and 52.9% vs. 3.4% and 6.9%, respectively (p<0.001). Disease free survival (DFS) at 1 and 3 years was 82.8% (95% CI 70.1-97.7) and 79.3% (95% CI 65.9-95.5) in the negative MRD group and 35.3% (95% CI 18.5-67.2) and 29.4% (95% CI 14.1-61.4) in the positive MRD group (p<0.001). With a median follow up of 29 months in the entire cohort and 177.6 months (14.8 years) in survivors, 1- and 3-year overall survival (OS) for the pre-HSCT negative MRD group was 82.8% (95% CI 70.1-97.7) and 79.2% (95% CI 65.6-95.5), respectively, compared to 64.7% (95% CI 45.5-91.9) and 41.2% (95% CI 23.3-72.7) in the positive MRD group (p=0.001). In a multivariate model, positive pre-HSCT MRD is associated with increased CIR and poorer DFS and OS.

Conclusion: These results support that pre-HSCT MRD should be eradicated to improve survival of adult ALL patients who undergo allo-HSCT.

Keywords: Acute lymphoblastic leukemia; Allogeneic hematopoietic stem cell transplantation; Citometría de flujo multiparamétrica; Enfermedad injerto contra huésped; Enfermedad medible residual; Graft versus host disease; Leucemia aguda linfoblástica; Measurable residual disease; Multiparametric flow cytometry; Quantitative polymerase chain reaction; Reacción en cadena de la polimerasa cuantitativa; Trasplante alogénico de células progenitoras hematopoyéticas.