Risk factors for post‐transplant lymphoproliferative disorder after Thymoglobulin‐conditioned hematopoietic cell transplantation

Abstract

Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD)occurs frequently when rabbit antithymocyte globulin (ATG) is used in hematopoietic cell transplant (HCT) conditioning. We retrospectively studied 554 patients undergoing ATG-conditioned myeloablative HCT. Strategies used to minimize mortality due to PTLD were either therapy of biopsy-diagnosed PTLD in the absence of EBV DNAemia monitoring (n = 266) or prompt therapy of presumed PTLD (based on clinical/radiologic signs and high EBV DNAemia, in the setting of weekly EBV DNAemia monitoring) (n = 199). Both strategies resulted in similar mortality due to PTLD (0.7% vs 1% at 2 years, P = .43) and similar overall survival (63% vs 67% at 2 years, P = .23) even though there was a trend toward higher PTLD incidence with the prompt therapy.Donor positive with recipient negative EBV (D+R−) serostatus was a risk factor for developing PTLD. Older patient age, HLA-mismatched donor, and graft-versus-host disease were not associated with increased risk of PTLD. In summary, in ATGconditioned HCT, D+R− serostatus, but not older age, mismatched donor or GVHD is a risk factor for developing PTLD. EBV DNAemia monitoring may be a weak risk factor for developing/diagnosing PTLD; the monitoring coupled with prompt therapy does not improve survival. K E Y W O R D SEpstein-Barr virus, post-transplant lymphoproliferative disorder, prompt therapy, rituximab

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

“…We observed an incidence of PTLD of 8.8% which is in keeping with incidences of 8%-10% reported with ATG-based GVHD prophylaxis. 33 PTLD in the setting of allo-SCT is strongly correlated with EBV DNAemia. 34 Pre-emptive treatment strategies with rituximab have been used to improve survival in patients at high risk for developing PTLD such as those receiving ATG or alemtuzumab in the conditioning regimen.…”

Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies

“…Based on European data, the incidence of PTLD after allogeneic HSCT was 3.2%, varying from 1.2% in MUDs to 2.8% in mismatched related donors (including haploidentical and mismatched related donors). In the context of ATG-based conditioning, the incidence of PTLD has been reported to be 9.7% [31]. The risk of developing EBV-PTLD is predominantly related to the degree of T cell depletion or impairment, as EBV-infected B cells are held in check by cytotoxic T cell lymphocytes.…”

“…This may have led to a higher rate of detection of EBV reactivation. EBV seromismatch has been described as a risk factor for PTLD development, and the selection of an EBV-matched donor may affect rates of reactivation in a manner similar to CMV [31]. There are no clear guidelines for the monitoring and preemptive treatment of EBV reactivation or PTLD in haploHSCT.…”

Make Sure You Have a Safety Net: Updates in the Prevention and Management of Infectious Complications in Stem Cell Transplant Recipients

“…Risk factors for EBV-associated PTLD are primarily related to immunosuppression and T-lymphocyte dysfunction, which may include T-cell depletion of the graft [139]. Other risk factors include EBV serodiscordance; seronegative recipients who receive HSCT from seropositive donors (D+/R-) are at greatest risk of developing PTLD with an odds ratio of up to 13.6, possibly due to uncontrolled EBV-infected lymphocyte proliferation in an EBV-naïve host [139][140][141].…”

“…Suggested EBV viral load cut-offs for rituximab range from 100 to 10,000 copies/mL [140,142,145,146]. In a retrospective study of 554 patients who underwent anti-thymocyte globulin-conditioned myeloablative HSCT, there was no difference in mortality between patients who received pre-emptive therapy based on EBV surveillance and those who were treated for biopsy-proven PTLD without EBV viral load monitoring; however, the viral load threshold for the pre-emptive group was relatively high at >40,000 DNA copies/mL [141]. In another retrospective study of 332 HCT recipients, a survival benefit was found for patients with EBV viral load ≥50,000 copies/mL who received rituximab [147].…”