Article

Spontaneous autologous graft-versus-host disease in plasma cell myeloma autograft recipients: flow cytometric analysis of hematopoietic progenitor cell grafts.

Department of Medicine, Division of Hematology/Oncology, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.15). 03/2011; 17(7):970-8. DOI: 10.1016/j.bbmt.2011.03.005
Source: PubMed

ABSTRACT Nine plasma cell myeloma patients spontaneously developed histologically proven autologous graft-versus-host disease (GVHD) limited predominantly to the gastrointestinal tract within 1 month of initial autologous hematopoietic cell transplantation (AHCT) using high-dose melphalan conditioning. All recipients responded promptly to systemic and nonabsorbable oral corticosteroid therapy. All patients previously received systemic therapy with thalidomide, lenalidomide, or bortezomib before AHCT. Using enzymatic amplification staining-enhanced flow cytometry, we evaluated expression of selected transcription regulators, pathway molecules, and surface receptors on samples of the infused hematopoietic cell grafts. We demonstrated significantly enhanced expression of GATA-2, CD130, and CXCR4 on CD34(+) hematopoietic progenitor cells of affected patients compared with 42 unaffected AHCT controls. These 3 overexpressed markers have not been previously implicated in autologous GVHD. Although we did not specifically evaluate T cells, we postulate that exposure over time to the various immunomodulating therapies used for induction treatment affected not only the CD34(+) cells but also T cells or relevant T cell subpopulations capable of mediating GVHD. After infusion, the affected hematopoietic progenitor cells then encounter a host that has been further altered by the high-dose melphalan preparative regimen; such a situation leads to the syndrome. These surface markers could be used to develop a model to predict development of this syndrome. Autologous GVHD potentially is a serious complication of AHCT and should be considered in plasma cell myeloma patients with otherwise unexplained gastrointestinal symptoms in the immediate post-AHCT period. Prompt recognition of this condition and protracted treatment with nonabsorbable or systemic corticosteroids or the combination may lead to resolution.

0 Bookmarks
 · 
109 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Engraftment syndrome (ES) is an increasingly observed, and occasionally fatal, complication after autologous peripheral blood stem cell transplantation (PBSCT). In this study, we demonstrate that the incidence of ES is significantly increased in patients undergoing autologous PBSCT for multiple myeloma in comparison to non-Hodgkin's lymphoma or Hodgkin's lymphoma. Multivariate analysis revealed that age >60 (hazard ratio [HR], 1.71 [95% confidence interval [CI], 1.12-2.62; p=0.013) and transplantation for multiple myeloma (HR, 2.80 [95% CI, 1.60-4.90]; p=0.0003) were associated with an increased risk of this complication. When stratified for myeloma patients only, age > 60 (HR, 1.80 [95% CI, 1.13-2.87]; p=0.013) and prior treatment with both lenalidomide and bortezomib (HR 1.83 [95% CI, 1.11-3.04]; p=0.0001) were associated with an increased incidence of ES. Conversely, lack of exposure to cyclophosphamide from either chemomobilization or as a component of the pretransplantation therapeutic regimen increased the risk of this complication (HR 3.05 [95% CI 1.91-4.87]; p<0.0001). These studies demonstrate that the pre-transplantation exposure of multiple myeloma patients to novel immunomodulatory agents and cyclophosphamide significantly affects the subsequent risk of developing ES.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2013; · 3.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The E2997 Phase III trial included preservation of valuable chronic lymphocytic leukemia (CLL) patient specimens and relevant clinical outcome data. Using a novel high-resolution technology on a flow cytometry platform, we assessed 79 E2997 samples for the expression of 27 analytes that reflected the activity of signaling pathways and apoptosis. We found that the expression levels of ZAP70 segregated the samples into two subpopulations with the distribution showing a peak-trough-peak configuration. Although prior assessment of ZAP70 by standard procedures did not reveal any prognostic information, we found by using the trough in the distribution as a cutpoint that ZAP70 expression levels were significantly correlated with both progression-free survival and overall survival. Additionally, the cells expressing high versus low levels of ZAP70 demonstrated distinct molecular organization as indicated by the other analytes assessed. Our analysis demonstrates the value of ZAP70 expression as a prognostic indicator and suggests that the different clinical results may be due to the distinct molecular biology of the ZAP70-low versus the ZAP70-high CLL samples. © 2014 International Society for Advancement of Cytometry
    Cytometry Part A 05/2014; · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autologous graft versus host disease (autoGVHD) is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs) used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC) products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B) were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3(+) cell number was significantly lower in autoGVHD patients compared to unaffected controls (P = 0.047). On subset analysis of CD3(+) cells, CD8(+) cells (but not CD4(+) cells) were found to be significantly lower in patients with autoGVHD (P = 0.038). HLA-B55 expression was significantly associated with development of autoGVHD (P = 0.032). Lower percentages of CD3(+) and CD8(+) T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.
    Bone marrow research. 01/2014; 2014:891427.

Full-text

View
1 Download
Available from
May 28, 2014