The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia

Abstract

Summary:Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre-and post-transplant serotherapy with Campath 1G (days ؊5 to ؉5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days ؊5 to ؊1 inclusive, with highdose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing Ͼgrade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 ؋ 10 8 /kg) were the most important factors predicting engraftment (P ‫؍‬ 0.03 and P ‫؍‬ 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P ‫؍‬ 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P ‫؍‬ 0.02) and disease status at transplantation (P ‫؍‬ 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P ‫؍‬ 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P ‫؍‬ 0.002). We conclude that pretransplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant-

Disease stage stratified effects of cell dose in unrelated BMT for hematological malignancies: a report from Japan marrow donor program

“…Although many studies reported that higher cell dose improved OS rates, 8,11,12,18,19 effects of cell dose on relapse and NRM rates were not consistent among studies probably because of the differences in diseases, stages and transplant procedures. Furthermore, it is not practical to analyze child and adult patients together because biology of disease, treatment protocols and harvested total nucleated cells per body wt are likely to differ between them.…”

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis

“…However, recent data from single institutions have shown outcomes after UD BMT approaching those achieved from MRD transplants. 1,8,11 These improved results appear to be at least partly due to improved matching techniques. For example, both acute GVHD and TRM are significantly less after transplants from UD matched by molecular methods for class II antigens.…”

“…6 In recent years, a number of European centers have reported relatively low rates of acute GVHD and early TRM using a variety of ATG products and schedules of administration. [7][8][9][10][11][12][13][14][15] Total doses of pretransplant thymoglobulin have ranged between 8 and 20 mg/kg. 8,9,12,13 An IBMTR analysis of alternative donor transplants between 1987 and 1993 indicated that the influence of donors on outcome was not apparent in high risk patients but quite significant with low and intermediate risk disease.…”

“…[1][2][3][4][5][6] In addition, some uncontrolled studies have indicated that pretransplant serotherapy with antithymocyte globulin (ATG) or other antibodies appears to reduce acute GVHD and early mortality of closely matched UD BMT to levels comparable to matched related donor (MRD) BMT. [7][8][9][10][11][12][13][14][15] Since 1995 we have used a relatively low dose of rabbit ATG in the pretransplant conditioning protocol for all UD transplants. Outcomes of 57 of these patients are compared with those of 57 MRD BMT recipients matched for important prognostic factors.…”

Reduced-intensity conditioned allogeneic haematopoietic stem cell transplantation results in durable disease-free and overall survival in patients with poor prognosis myeloid and lymphoid malignancies: eighty-month follow-up

“…In unrelated donor transplants, the use of ATG for in vivo T-cell depletion was found to be useful by some but not by others 25,26 Bacigalupo et al 27 reported a randomized prospective study of the use of ATG in unrelated donor marrow transplantation and found that though the risk of grade III-IV acute GVHD is markedly reduced in the ATG cohort, this does not result in the reduction of treatment-related mortality because of an increased risk of infections. They also noted that though the survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.…”