Association of MRD Status With Survival Outcomes and Cytokine Release Syndrome in Outpatient Transplantation After Reduced-Intensity Conditioning for Acute Lymphoblastic Leukemia: Experience From a Low- and Middle-Income Country Reference Center.

OBJECTIVE

To establish the relationship of minimal residual disease (MRD) status with survival outcomes after outpatient hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) in patients with acute lymphoblastic leukemia (ALL).

MATERIAL AND

METHODS

A single-center retrospective study including 145 ALL patients who received peripheral blood (PB) RIC HSCT was carried out. MRD was measured by multiparametric flow cytometry (MFC) before and within 100 days after HLA-identical or haploidentical transplantation, with >0.01% leukemic cells considered a positive MRD result. Overall survival (OS) and relapse-free survival (RFS) were estimated by the Kaplan-Meier method, associations with clinical variables were calculated by Cox regression analysis, and competing risks were determined with Fine-Gray models.

RESULTS

Before transplantation, 32 (22.06%) patients were MRD positive, 16 (50%) relapsed, and 16 (50%) died, whereas 24 (16.1%) were MRD positive after HSCT, 17 (70.8%) relapsed, and 15 died (62.5%). Eleven patients were MRD positive before and after HSCT; 7 (63.6%) relapsed, and 8 (72%) died. In multivariate analysis, a higher risk for lower OS was found in patients who relapsed (hazard ratio [HR] = 5.04, P = .001) and a higher risk was found for lower RFS in those with post-HSCT MRD positive (HR = 2.11, P = .034). No differences according to acute graft-versus-host disease (GVHD) were identified, whereas chronic GVHD led to higher RFS. In univariate analysis, pre-HSCT MRD positive was associated with lower RFS. A positive MRD status after HSCT was associated with cytokine release syndrome (CRS) (HR = 4.25, P = .019), clinical stage (HR = 0.16, P = .044), and mucositis (HR = 4.45 P = .040).

CONCLUSION

An MRD-positive status after hematopoietic stem cell transplantation was associated with lower survival outcomes and with CRS development.