Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

Bone Marrow Transplant. 2013 May;48(5):708-14. doi: 10.1038/bmt.2012.211. Epub 2012 Oct 29.

Abstract

We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days +15, +30, +60 and +100 with the outcomes. Multivariate analysis revealed that day +100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P=0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P=0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, P<0.001). No patient in cluster C had a day +100 AMC >300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day +100 post fludarabine/melphalan-conditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Hematologic Neoplasms / blood*
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Lymphocytes / immunology*
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Monocytes / immunology*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Young Adult

Substances

  • Antineoplastic Agents, Alkylating
  • Vidarabine
  • fludarabine
  • Melphalan