title: Posttransplantation lymphoproliferative disorders in bone marrow transplant recipients are aggressive diseases with a high incidence of adverse histologic and immunobiologic features.
abstract: Posttransplantation lymphoproliferative disorders (PT-LPDs) occurring in T-cell depleted (TCD) allogeneic bone marrow transplant recipients seem to be different from those that arise in solid organ recipients in their early development, the high incidence of extensive dissemination at presentation, and their aggressive course and high fatality rate. We report a series of 10 patients with PT-LPDs after TCD allogeneic bone marrow transplant. We studied the correlation between the morphology of the lesions; their clonality based on immunoglobulin (Ig) heavy chain gene rearrangement analysis and immunohistochemistry; their proliferative activity as measured by immunoperoxidase staining for the proliferating cell nuclear antigen (PCNA) and the presence of p53 gene product overexpression. Histologically, our cases corresponded to the two morphologic categories of polymorphic B-cell lymphoma (PBCL, seven cases) and malignant lymphoma immunoblastic (ML-IB, three cases). Ig light-chain staining showed monoclonality in a minority of the cases, whereas Ig gene rearrangement analysis by polymerase chain reaction revealed B-cell clonality in three of seven cases of PBCL and in all three cases of ML-IB. The Epstein-Barr virus (EBV) genome, the expression of EBV latent membrane protein or both were found in all 10 specimens. High proliferative activity (PCNA > or = 66%) was found in all cases, with a mean PCNA value of 56% in PBCL and 84% in ML-IB. Five specimens were p53+ (two of seven PBCL and three of three ML-IB). Two of four PBCL cases resolved with the administration of donor leukocytes. All of the remaining patients died of the PT-LPD within a short time from admission. Our results show that the PT-LPDs after TCD bone marrow transplantation are characterized by a high frequency of high-grade histologic subtypes, frequent monoclonality, high proliferative activity, frequent overexpression of p53 gene product, and poor prognosis. These characteristics observed in only a minority of cases of PT-LPDs occurring after solid organ transplantation may account for the less aggressive clinical behavior observed in those diseases.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
authors.forename: A
authors.initials: A
authors.lastname: Orazi
authors.forename: R A
authors.initials: RA
authors.lastname: Hromas
authors.forename: R S
authors.initials: RS
authors.lastname: Neiman
authors.forename: T C
authors.initials: TC
authors.lastname: Greiner
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Rubin
authors.forename: S
authors.initials: S
authors.lastname: Haskins
authors.forename: N A
authors.initials: NA
authors.lastname: Heerema
authors.forename: V
authors.initials: V
authors.lastname: Gharpure
authors.forename: R
authors.initials: R
authors.lastname: Abonour
authors.forename: E F
authors.initials: EF
authors.lastname: Srour
authors.forename: K
authors.initials: K
authors.lastname: Cornetta
mesh_terms: D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D017931:DNA Primers / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D015994:Incidence; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D004279:DNA, Viral; D007143:Immunoglobulin Heavy Chains; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53