Transplant dose of CD34⁺ and CD3⁺ cells predicts outcome in patients with haematological malignancies undergoing T cell‐depleted peripheral blood stem cell transplants with delayed donor lymphocyte add‐back

Abstract

Summary. We sought to optimize and standardize stem cell and lymphocyte doses of T cell-depleted peripheral blood stem cell transplants (T-PBSCT), using delayed add-back of donor T cells (DLI) to prevent relapse and enhance donor immune recovery. Fifty-one patients with haematological malignancies received a T-PBSCT from an HLA-identical sibling, followed by DLI of 1 Â 10 7 and 5 Â 10 7 CD31 cells/kg on d 145 and 1100 respectively. Twenty-four patients were designated as standard risk and twenty-seven patients with more advanced leukaemia were designated as high risk. Median recipient age was 38 years (range 10± 56). Median (range) of CD34 1 and CD3 1 cell transplant doses were 4´6 (2´3±10´9) Â 10 6 /kg and 0´83 (0´38± 2) Â 10 5 /kg respectively. The cumulative probability of acute GVHD was 39%. No patient died from GVHD or its consequences. The probability of developing chronic GVHD was 54% (18% extensive). The probability of relapse was 12% for the standard-risk patients and 66% for high-risk patients. In multivariate analysis, the risk factors for lower disease-free survival and overall survival were high-risk disease, CD341 dose , 4´6 Â 10 6 /kg and CD3 1 dose , 0´83 Â 10 5 /kg. Predictive factors for chronic GVHD were a T-cell dose at transplant . 0´83 Â 10 5 CD3 1 cells/ kg. These results further define the impact of CD34 and CD3 cell dose on transplant outcome and show that careful dosing of stem cells and lymphocytes may permit the control and optimization of transplant outcome.

Impact of transplanted CD34+ cell dose in allogeneic unmanipulated peripheral blood stem cell transplantation

“…6,7 However, the clinical relevance of the number of CD34+ cells from bone marrow differs from that from PBSCT. Although a higher dose of CD34+ cells produces better clinical results in allogeneic BMT settings, 5,16 the same results cannot be assumed with allogeneic unmanipulated PBSCT because of the higher incidence of life-threatening extensive cGVHD.…”

“…5,6 However, a recent study 7 suggested that transplantation with a higher CD34+ cell dose was detrimental in terms of chronic GVHD (cGVHD) in allogeneic CD34+ cell-selected peripheral blood stem cell transplantation (PBSCT). Moreover, this association may also exist in the context of allogeneic unmanipulated PBSCT where a higher T-cell content or extremely high dose of CD34+ cells can be involved.…”

Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia

“…on May 10, 2018. by guest www.bloodjournal.org From here. [39][40][41] Higher CD34 doses are generally associated with reduced TRM and relapse rates and superior survival and LFS rates. [42][43][44][45][46][47] However, the infusion of high doses of CD34 cell has also been associated with an increased rate of acute and or chronic GVHD.…”

Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8+CD3+ count reconstitution is associated with survival

“…Among the factors known to influence immune reconstitution are the stem cell source, the amount of CD34 þ cells and the content of CD3 þ cells in the graft, 3,5,6,[18][19][20][21] the cytomegalovirus status before and after SCT, 6,8,22 the additional application of donor lymphocyte infusion, 9,23,24 the relationship and disparity between donor and recipient, 23,25,26 the age of the patients, 9,21,22 and the development of GvHD. 18,22,27 The influence of the stem cell source on the speed of immunological recovery has been controversial.…”