Posttransplant Lymphoproliferative Disorder Following Nonmyeloablative Allogeneic Stem Cell Transplantation

Abstract

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST). This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003. Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal. The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.

EBV-related disease following haematopoietic stem cell transplantation with reduced intensity conditioning

“…Of 15 patients described in the literature (see Table IV), six received no specific therapy and died [8,48,50,51]. In four further cases, rituximab therapy was initiated but was unsuccessful [8,48,50]. A patient who received DLI alone to treat EBV viraemia of 2.5610 6 copies EBV DNA/ml died, and subsequently had PTLD demonstrated at post-mortem biopsy [52].…”

“…PTLD has been diagnosed both during life (either on biopsy or with molecular evidence of EBV infection with radiological finding consistent with PTLD) and in certain cases only at post-mortem biopsy. Of 15 patients described in the literature (see Table IV), six received no specific therapy and died [8,48,50,51]. In four further cases, rituximab therapy was initiated but was unsuccessful [8,48,50].…”

“…A summary of the clinical presentation, treatment and outcome of reported cases of PTLD following RIC is shown in Table IV. PTLD has been seen as both localised and disseminated lymphomatous disease. Localised disease has included cervical lymphadenopathy [50]and abdominal disease [49,50]. PTLD has been diagnosed both during life (either on biopsy or with molecular evidence of EBV infection with radiological finding consistent with PTLD) and in certain cases only at post-mortem biopsy.…”

Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic stem cell transplant patients

“…7,11,19,29 Severe acute GVHD and the use of intensive immunosuppression, especially ATG, increased the risk of EBV viremia in the present study. The overall incidence of EBV-DNAemia was in accordance with results of previous studies.…”

Examining the Origin of Posttransplant Lymphoproliferative Disorder in a Patient After a Second Allogeneic Hematopoeitic Stem Cell Transplantation for Relapsed BCR-ABL Positive Acute Lymphoblastic Leukemia

“…In contrast to the cases described above, 5,6 the 2 PTLDs in these patients were of the expected donor origin. 8 Reddiconto et al 9 also used STR analysis for examining the origin of PTLD after cord blood transplantation and described a 31-year-old man with therapy-associated myelodysplastic syndrome with 7q deletion after chemotherapy for a nonHodgkin lymphoma. The patient received a cord blood transplantation using 2 unrelated 4/6 HLA-matched cord blood units.…”