scholarly journals The evolution of T-cell depletion in haploidentical stem-cell transplantation

2015 ◽  
Vol 172 (5) ◽  
pp. 667-684 ◽  
Author(s):  
Noga Or-Geva ◽  
Yair Reisner
2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS. Conclusion: Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Salem Alshemmari ◽  
Reem Ameen ◽  
Javid Gaziev

Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA-matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5418-5418
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Cecile Du Toit ◽  
Andrew McDonald

Abstract Haematopoietic stem cell transplantation may be curative therapy for selected patients with haematological malignancies. We reviewed our experience in individuals with lymphoid neoplasms (excluding multiple myeloma) who received an allogeneic stem cell transplant from HLA identical sibling donors. Myeloablative conditioning was radiation based (n= 46) or with chemotherapy (n= 12). GvHD prophylaxis was with T-cell depletion (CAMPATH-1 g or H,“ in the bag”). 17 received a BMT while 41 had PBPC (median CD34+ 2.64). Patients receiving BMT had no further immunosuppression, while 12 patients who received PBPC grafts received prednisone 30 mg and another 21 were treated with therapeutic doses of cyclosporine for 90 days. The diagnosis was indolent lymphoma in 14 (median 3 treatment modalities), aggressive variant in 18 (7 with transformed DLBC; 6 with lymphoblastic lymphoma, 2 mantle cell), 5 had chemotherapy responsive (median 4 treatments) recurrent Hodgkin’s lymphoma and 21 had lymphoblastic leukaemia (18 in CR1). Median age was younger in patients with ALL (24 years; range 15–45) than lymphoma (47 years; 29–57; p&lt; 0.001). At a median follow up of 1173 (32–5598) days, 20 have died and 67% survive disease free. Death was from disease recurrence in 15 (10 with ALL), and it was transplant related in 4 while one patient died of AIDS. Survival was significantly worse in patients with lymphoblastic leukaemia (48%; p&lt; 0.001), while 76% of those with lymphomas survive in unmaintained remission (median 1493 days; 32–5598). Survival was significantly associated with diagnosis of lymphoma (p&lt; 0.01), CD34+ cell number above median (p= 0.04) and absence of GvHD (p&lt; 0.01). We conclude that despite T-cell depletion allogeneic stem cell transplantation is very effective therapeutic strategy in patients with lymphoma, as disease recurrence was low (relapse 6/37; p= 0.03), suggesting remaining graft vs. lymphoma effect. To the contrary, this therapy remains less satisfactory for patients with ALL who have poor prognostic factors.


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