Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation

Abstract

Introduction:The objective of this study was to investigate the clinical significance of minimal residual disease (MRD) monitoring through Wilms tumor 1 (WT1) gene expression and multicolor flow cytometry (FCM) in patients with chronic myelomonocytic leukemia (CMML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods: For this purpose, WT1 gene expression and the CMML-related abnormal immunophenotype were examined using real-time quantitative polymerase chain reaction and FCM, respectively. Results:In total, 59 patients with CMML who underwent allo-HSCT were enrolled in this study. Thirteen cases (22.0%) developed hematological relapse, and 15 patients (25.4%) expired during the follow-up period. Thirty-four patients (37.6%) were positive for WT1 (WT1+), and 44 patients (74.6%) were positive for FCM prior to allo-HSCT. After allo-HSCT, there were 21 WT1+ patients (35.6%) and 10 patients (16.9%) who were positive in FCM (FCM+). Post-transplant WT1+ (post-WT1 0.6+; 50.7% vs. 7.6%, p < .001) and post-transplant FCM+ (post-FCM+; 90.0% vs. 8.8%, p < .001) indicated a higher 3-year cumulative incidence of relapse (CIR) compared with the WT1− or FCM−patients. Multivariate analysis of event-free survival (EFS), overall survival (OS), and CIR showed that the FCM status after transplantation was an independent prognostic factor for relapse (p < .05). Conclusion:Both FCM and WT1 after HSCT were identified as important predictors of recurrence of CMML following transplantation and may be useful in guiding interventions against disease relapse.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

“…According to CMML epidemiological statistics, almost 90% of cases occur in patients older than 60 years 4,35,50 . We reviewed the literatures on the age of CMML patients in Western (Germany, 29,30,51 France, 13,19,52 America, 8,11,12,15,17,20,25,26,28,40,53,54 Italy, 39,55 Greece, 14 and Denmark, 24 ) and Eastern countries (Japan 16,22,27 and China, 6,43,49,56–63 ), and the results showed that the median age of CMML patients in Eastern countries was younger (38–70 years vs. 44–73 years), and the median age of CMML patients undergoing allo‐HSCT was similar in Eastern and Western countries (38–63 years vs. 44–64 years). However, the age of CMML patients undergoing allo‐HSCT was lower in both Eastern and Western countries.…”

Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders

“…Some authors found it to be predictable, whereas other did not (23,24,35,47). However, newer prognostic tools have been proposed, such as the CPSS-mol, the CPSS-P, and the CPSS transplantspecific, which have incorporated the prognostic importance of mutations that can predict outcome in transplanted patients, as this has been shown in several retrospective studies (23,50,74,91,93). Using these tools might help to better distinguish the transplantation risk group.…”

“…Both techniques demonstrated a high level of prognostic value and could predict posttransplant relapse. The significance of the presence of WT1 mutations was not investigated (91).…”

Definitions, Biology, and Current Therapeutic Landscape of Myelodysplastic/Myeloproliferative Neoplasms

“…Patients with a detectable mutation pre-and post-transplant had a higher incidence of relapse (50%) than those in which the mutation was only detected before the transplant but not after (15%) [153]. These molecular markers, the CSF3R T618I mutation, and the detection of MRD with PCR for WT1 or flow cytometry can be used as predictors of relapse post-transplant [154,155].…”