Minimal residual disease monitoring and preemptive immunotherapy in myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation

Ann Hematol. 2016 Aug;95(8):1233-40. doi: 10.1007/s00277-016-2706-y. Epub 2016 Jun 14.

Abstract

This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs. 6.1 %, P = 0.040) or FCM (62.5 vs. 3.6 %, P < 0.001) indicated a higher 2-year relapse rate. Twenty-one patients met our combined criteria for MRD, and the presence of MRD was associated with a higher 2-year relapse rate (27.3 vs. 4.5 %, P = 0.003). Preferentially expressed antigen of melanoma (PRAME) expression alone was not an appropriate MRD marker; however, it suggested that the MRD-positive patients may fail to respond to preemptive immunotherapy. In patients positive for both PRAME and MRD, the relapse rate was 60 % despite preemptive immunotherapy. Multivariate analysis confirmed the association between the increased relapse rate and positivity for both PRAME and MRD (hazard ratio = 42.8, P = 0.001). MRD monitoring predicted relapse in high-risk MDS post-HSCT patients, and PRAME- and MRD-positive patients did not benefit from preemptive immunotherapy.

Keywords: Allogeneic hematopoietic stem cell transplantation; Minimal residual disease; Myelodysplastic syndromes; Preferentially expressed antigen of melanoma; Wilms’ tumor gene 1.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Neoplasm / genetics
  • Child
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunophenotyping
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / therapy*
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / metabolism
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transplantation, Homologous
  • WT1 Proteins / genetics

Substances

  • Antigens, Neoplasm
  • PRAME protein, human
  • WT1 Proteins
  • WT1 protein, human