Adult Recipients of Matched Related Donor Blood Cell Transplants Given Myeloablative Regimens Including Pretransplant Antithymocyte Globulin Have Lower Mortality Related to Graft-versus-Host Disease: A Matched Pair Analysis

Russell, James A.; Turner, A. Robert; Larratt, Loree; Chaudhry, Ahsan; Morris, Donald G.; Brown, Christopher B.; Quinlan, Dan; Stewart, Douglas A.

doi:10.1016/j.bbmt.2006.10.017

Cited by 71 publications

(72 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[29][30][31][32] Administration of rabbit-anti-human T lymphocyte antibodies has been increasingly used by transplant programs because the antibodies can partially prevent aGVHD and cGVHD without impacting rates of relapse and non-EBV infections (except when used at a high dose, for example, 48 mg/kg thymoglobulin). 9,20,[33][34][35][36][37][38][39][40][41] Thus, our findings that in patients conditioned with rabbit-ATG, the PTLD occurrence is relatively high (8.1%) and that the vast majority of PTLD's occurring before day 100 are important. This suggests that monitoring EBV DNAemia in the first 100 days is warranted, together with preemptive (at the time of high/rising EBV DNAemia) or prompt (early in the course of PTLD) administration of rituximab- [42][43][44] or EBV-specific T lymphocytes.…”

Section: Discussionmentioning

confidence: 69%

“…21 All patients received rabbit-ATG (thymoglobulin, Genzyme, Mississauga, Ontario, Canada) 0.5 mg/kg on day À2, 2.0 mg/kg on day À1 and 2.0 mg/kg on day 0 (total, 4.5 mg/kg). 20 Table 1 displays patient and donor characteristics. Supportive care was similar for all patients.…”

Section: Methodsmentioning

confidence: 99%

“…20 Conditioning of some patients included TBI (4 Gy). 21 All patients received rabbit-ATG (thymoglobulin, Genzyme, Mississauga, Ontario, Canada) 0.5 mg/kg on day À2, 2.0 mg/kg on day À1 and 2.0 mg/kg on day 0 (total, 4.5 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28-770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…Dose-finding studies for ATG have been performed in the HLAidentical sibling donor (ISD) setting [11][12][13] and unrelated donor (URD) setting. 2,4,[14][15][16] A total dose of 4.5-5 mg/kg and 7.5 mg/kg ATG has been recommended in the ISD and the URD settings, respectively.…”

Section: Discussionmentioning

confidence: 99%

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Wang

et al. 2013

Bone Marrow Transplant

104

131

View full text Add to dashboard Cite

To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P ¼ 0.005, 95% CI for the difference, À 19.4% to À 3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P ¼ 0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P ¼ 0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD. INTRODUCTIONAntithymocyte globulin (ATG) has been used in the conditioning regimen to prevent severe GVHD in haploidentical hematopoietic SCT (HSCT), and our previous study presented encouraging results. 1 However, the limitations associated with the use of ATG as a regimen for in vivo T-cell depletion (TCD) include the occurrence of delayed immune reconstitution and an increased risk of severe infections, depending on the dose of ATG administered. 2 Several previous studies have suggested suitable doses of ATG in matched unrelated transplantations. 3,4 However, to date, the optimal dose of ATG with respect to the prevention of severe GVHD following the haploidentical transplantation is unknown.In our recently reported retrospective study, we reduced the total dose of ATG from the traditional 10 mg/kg in our classic regimen to 6 mg/kg for refractory/relapsed patients undergoing haploidentical HSCT. We observed that the reduction of the total dose of ATG to 6 mg/kg produced similar rates of engraftment, GVHD and survival compared with the 10 mg/kg dose of ATG. 5 Based on these findings, we set out to extend the use of 6 mg/kg ATG to standard-risk patients. Therefore, we initiated the current prospective randomized study to evaluate the effect of the two different doses of ATG in conditioning regimens on graft failure, GVHD, relapse and survival among standard-risk patients receiving haploidentical HSCT. We postulated that the use of 6 mg/kg ATG might reduce adverse events without increasing the risk of GVHD.

show abstract

“…1 However, a study conducted at the City of Hope Cancer Center using CSA and MMF in patients who had undergone reduced-intensity URD hematopoietic cell transplantation showed high rates of both acute and chronic GVHD. 2 In an attempt to improve on our earlier experience, and based on emerging data using thymoglobulin, 3,4 we conducted a prospective clinical trial using thymoglobulin added to CSA/MMF as GVHD prophylaxis.…”

mentioning

confidence: 99%

Thymoglobulin, CYA and mycophenolate mofetil as GVHD prophylaxis for reduced-intensity unrelated donor hematopoietic cell transplantation: beneficial effect seen on chronic GVHD

Rodríguez

Nademanee

Palmer

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

Adult Recipients of Matched Related Donor Blood Cell Transplants Given Myeloablative Regimens Including Pretransplant Antithymocyte Globulin Have Lower Mortality Related to Graft-versus-Host Disease: A Matched Pair Analysis

Cited by 71 publications

References 27 publications

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial

Thymoglobulin, CYA and mycophenolate mofetil as GVHD prophylaxis for reduced-intensity unrelated donor hematopoietic cell transplantation: beneficial effect seen on chronic GVHD

Contact Info

Product

Resources

About