Improvement in rejection, engraftment rate and survival without increase in graft‐versus‐host disease by high marrow cell dose in patients transplanted for aplastic anaemia

Abstract

Two hundred and fifty-two consecutive patients with severe aplastic anaemia were conditioned by cyclophosphamide and given marrow transplants from HLA-identical siblings or parents. The results were analysed to examine the influence of marrow cell dose on graft rejection, speed of engraftment, survival and acute and chronic graft-versus-host disease (GVHD). Sixty patients received a corrected marrow cell dose below 2.2 x 10(8) nucleated cells per kg body weight, 73 patients between 2.2 and 3.2 x 10(8) cells/kg, 60 patients between 3.3 and 4.2 x 10(8) cells/kg, and 59 patients more than 4.2 x 10(8) cells/kg. The significant association between high marrow cell dose and low risk of graft rejection previously reported was confirmed. In addition, high marrow cell dose resulted in small but statistically significant reductions in time to granulocyte and platelet recoveries in patients with sustained engraftment. High marrow cell dose was also associated with a significant improvement in patient survival, a result solely due to the reduction in the incidence of graft rejection. Neither acute nor chronic GVHD were influenced by marrow cell dose. We conclude that the maximum marrow cell dose should be transplanted in patients with severe aplastic anaemia. Maximum marrow cell doses are likely to decrease the incidence of graft rejection, shorten the time to engraftment thereby decreasing the need for blood products and antibiotic support, and improve overall patient survival.

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

“…15,16 Some researchers have considered the total mononuclear cell count as a variable with potential influence on graft failure and OS. 5,6,[17][18][19] Other published studies to date have not included CD34 þ cell dose in their analysis. [20][21][22][23][24] We used the median CD34 þ count to define the cutoff to ensure an even distribution of patients in the low-and high-dose arms.…”

“…5,6 The importance of infusing at least 3 Â 10 8 /kg of total nucleated cells has been well recognized. A significant increase in the incidence of graft failure and a reduction in OS have been shown at doses below this threshold.…”

“…A significant increase in the incidence of graft failure and a reduction in OS have been shown at doses below this threshold. [5][6][7] We evaluated the influence of CD34 þ cell dose on the outcome of transplantation in 46 patients with acquired AA. The effects on haematological engraftment, graft failure, chimerism, transfusion dependency, GVHD and OS were compared by classifying patients into those who received a high cell dose and those who received a low cell dose.…”

Transplantation of Allogeneic Peripheral Blood Stem Cells Mobilized by Recombinant Human Granulocyte Colony Stimulating Factor

“…Experimental animal data have indicated that increasing the number of donor hematopoietic progenitor cells in the graft improves the probability of engraftment across an allogeneic mismatched barrier [81]. There are also data from patients with aplastic anemia receiving HLAidentical transplants demonstrating a decrease in rejection and an improved survival with the infusion of high marrow cell doses [82]. The number of donor hematopoietic cells available from marrow harvesting is limited and often suboptimal.…”

Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts

“…The 52 patients in the death infused into the patient essentially unmanipulated except as category also included a number of patients who received required for donor-recipient ABO blood group incompatisecond marrow infusions, whereas the 47 additional bility. 21 The murine anti-CD52 monoclonal antibodies patients who received top-up marrow represent those who Campath-1G or Campath-1M (kindly provided by Drs G either survived the first 3 months or, if they died within 3 Hale and H Waldmann, Cambridge, UK), were used to months, did not do so primarily because of infection, deplete the donor marrow of T cells in most cases, 22 while hemorrhage or graft failure.…”