Work

The Prognostic Role of Pretransplant Serum Lactate Dehydrogenase Levels in Acute Myeloid Leukemia and Lymphoma Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation

Year: 2020

Type: article

Abstract: Background Risk stratification is a critical step when considering allogeneic hematopoietic stem cell transplantation (HSCT). While Lactate dehydrogenase (LDH) is a readily available biomarker with a prognostic role in the front-line therapy setting of hematological malignancies, its' role in the pretransplantation setting is undefined. Methods This was a retrospective study on a cohort of patients who underwent allogeneic-HSCT at a single center between 2000 and 2016. Pre transplant LDH levels and other clinical features were extracted from medical record. The primary outcome was overall survival (OS), and secondary outcomes included non-relapse mortality (NRM) and relapse (considered as competing events). The median follow-up time was 59 months (IOR 27 - 112). We analyzed the association between median LDH levels, per disease category. Associations meeting a p-value below 0.05 for the primary outcome were further explored in a multivariable Cox regression (cause-specific Cox for competing events). The model was adjusted for age, disease risk index (DRI), year of HSCT, donor type, and conditioning regimens. Results A total of 1,250 adult (median age 52.8 years) patients with the following disease were included; Acute myeloid leukemia (AML, n=594; 48%), non-Hodgkin lymphoma (NHL, 211, 16.9%), acute lymphoblastic leukemia (ALL, n=175, 14%), myelodysplastic syndrome (n=165, 13%), and plasma cell dyscrasia (PCD, n=105, 8%). In the univariate analysis, AML patients with higher than median LDH levels (>193 IU/L) had lower 3-year OS (51.9% vs. 39.2%, p<0.001) (Fig.1A), and higher cumulative incidence of NRM (15.7% vs. 19.6%, p<0.04), and relapse incidence (RI) (26.7% vs. 40.7%, p<.0001). In a cubic spline (Fig.1B), we showed that the relationship between increasing LDH and reduced OS was linear (p<0.001). Higher LDH maintained its prognostic capacity in the multivariable Cox model (OS: hazard ratio [HR] 1.34 95% CI [1.06-1.7], NRM: [HR] 1.31 95% CI [0.87-1.98], RI: [HR] 1.42 95% CI [1.07-1.89]). In a univariate analysis of NHL patients, LDH levels above median value (>228 IU/L) was associated decreased OS (51.9% vs. 39.2%, p<.0001) (Fig.1C), and increased RI (17.1% vs. 29.2%., p=0.02), but not NRM. Using a cubic spline (Fig.1D), the association between LDH and mortality was also linear (p=0.007). Other malignancies did not reach statistical significance. Conclusion Using a systematic approach, we showed that pre-transplantation LDH is a potent biomarker that could be used for risk stratification for AML and NHL patients who are candidates for allogeneic-HSCT. While further validation is warranted it may be rewarding to incorporate LDH in future prognostic models assessing the risk of transplantation.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2019.12.620