T cell depletion and no post transplant immune suppression allow separation of graft versus leukemia from graft versus host disease

2019 ◽  
Vol 54 (S2) ◽  
pp. 775-779 ◽  
Author(s):  
Antonio Pierini ◽  
Loredana Ruggeri ◽  
Antonella Mancusi ◽  
Alessandra Carotti ◽  
Franca Falzetti ◽  
...  
2001 ◽  
Vol 19 (4) ◽  
pp. 1152-1159 ◽  
Author(s):  
Robert J. Soiffer ◽  
Edie Weller ◽  
Edwin P. Alyea ◽  
Peter Mauch ◽  
Iain L. Webb ◽  
...  

PURPOSE: The role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis. PATIENTS AND METHODS: Median age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 points) or 4.5 Gy (26 points) of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment. RESULTS: All 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 × 106/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P = .002), cytomegalovirus seronegative status (P = .04), and early disease status at bone marrow transplant (P = .05) were associated with superior survival. CONCLUSION: CD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.


2020 ◽  
Vol 140 (7) ◽  
pp. 1455-1459.e6
Author(s):  
Lukas Freund ◽  
Stephanie Oehrl ◽  
Galina Gräbe ◽  
Patrick Gholam ◽  
Thomas Plum ◽  
...  

Biomedicines ◽  
2017 ◽  
Vol 5 (4) ◽  
pp. 35 ◽  
Author(s):  
Haitham Abdelhakim ◽  
Hisham Abdel-Azim ◽  
Ayman Saad

Blood ◽  
2005 ◽  
Vol 106 (9) ◽  
pp. 3308-3313 ◽  
Author(s):  
Steven Z. Pavletic ◽  
Shelly L. Carter ◽  
Nancy A. Kernan ◽  
Jean Henslee-Downey ◽  
Adam M. Mendizabal ◽  
...  

AbstractDonor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P = .27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P = .29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P = .27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD.


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