title: Spontaneous autologous graft-versus-host disease in plasma cell myeloma autograft recipients: flow cytometric analysis of hematopoietic progenitor cell grafts.
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.
authors: Department of Medicine, Division of Hematology/Oncology, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA. hillard.lazarus@case.edu
authors: Hillard M
authors: HM
authors: Lazarus
authors: Scott R
authors: SR
authors: Sommers
authors: Lisa M
authors: LM
authors: Arfons
authors: Pingfu
authors: P
authors: Fu
authors: S A
authors: SA
authors: Ataergin
authors: N M
authors: NM
authors: Kaye
authors: F
authors: F
authors: Liu
authors: Tamila L
authors: TL
authors: Kindwall-Keller
authors: Brenda W
authors: BW
authors: Cooper
authors: Mary J
authors: MJ
authors: Laughlin
authors: Richard J
authors: RJ
authors: Creger
authors: Paul M
authors: PM
authors: Barr
authors: Stanton L
authors: SL
authors: Gerson
authors: David
authors: D
authors: Kaplan
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D016022:Case-Control Studies; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis; D005260:Female; D050989:GATA2 Transcription Factor / Q000096:biosynthesis; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000601:surgery*; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011719:Pyrazines / Q000627:therapeutic use; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D014182:Transplantation, Autologous / Q000009:adverse effects*
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D001897:Boronic Acids; C527276:CXCR4 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; C494199:IL6ST protein, human; D011719:Pyrazines; D019718:Receptors, CXCR4; D050822:Cytokine Receptor gp130; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide; D008558:Melphalan