Favourable effect of the combination of acute and chronic graft‐versus‐host disease on the outcome of allogeneic peripheral blood stem cell transplantation for advanced haematological malignancies

Abstract

Summary. To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n 70) or lymphoproliferative disorders (n 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1±61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26± 42%), 41% (95% CI, 33±49) for patients without GVHD and 14% (95% CI, 3±25) (P 0´001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2±49), 60 (44%) patients remained alive with an actuarial probability of overall survival and diseasefree survival (DFS) at 30 months of 31% (95% CI, 21±41%) and 28% (95% CI, 17±39%) respectively. In patients surviving . 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38±76%) compared with a DFS of 34% (95% CI, 17±51%) in the remaining patients (P 0´03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS.

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

“…Zaucha et al 13 observed that higher doses of CD34+ cells (48.0 Â 10 6 /kg) were associated with a significantly increased risk of extensive cGVHD (HR ¼ 2.3%, 95% confidence interval 1.4-3.7, P ¼ 0.001), rather than a demonstrable impact on survival and relapse. Yet, their results differ from previously published studies 10,20 that report on an inverse association between cGVHD and the risk of relapse, suggesting that the GVL effect carried by allogeneic PBSC grafts is not further improved when clinical symptoms of extensive cGVHD develop. A study 21 conducted by the International Bone Marrow Transplant Registry also inferred that the increased severity of chronic GVHD was not linked to a reduced risk of relapse among HLA-identical siblings receiving conventional stem cell transplantations.…”

“…In a previous study, 10 cGVHD was associated with a decreased risk of relapse and no significant increase in deaths in complete remission, thereby leading to an increased duration of both disease-free survival and overall survival through the induction of a strong GVL effect in patients with advanced leukemia. Intentional cGVHD or a GVL effect is needed in specific clinical situations where standard allogeneic transplantation by itself does not lead to good survival, such as high-risk ALL (pre-B ALL or Philadelphia chromosome positive ALL), primary refractory leukemia, or CML in blastic crisis.…”

“…This lower relapse rate could be explained by the so-called 'stem cell competition effect', where, after transplantation, residual clonogenic tumor cells are displaced by rapidly expanding normal stem cells, thereby representing another possible graft-vs-leukemia (GVL) effect as distinct from GVHD. 10 However, the long-term negative effects of high numbers of CD34+ cells in an allogeneic SCT setting have recently been questioned. Urbano-Ispizua et al 7 suggested that higher CD34+ cell doses (43 Â 10 6 /kg) may be associated with a higher transplant-related mortality (TRM) than a lower dose (1-3 Â 10 6 /kg) in allogeneic CD34+ cell-selected PBSCT from HLA-identical sibling donors.…”

“…Several groups [10][11][12] advocate that the relapse rate is lower in recipients who receive a higher stem cell dose or PBSC than in patients who receive a lower stem cell dose or bone marrow cells for allogeneic SCT. This lower relapse rate could be explained by the so-called 'stem cell competition effect', where, after transplantation, residual clonogenic tumor cells are displaced by rapidly expanding normal stem cells, thereby representing another possible graft-vs-leukemia (GVL) effect as distinct from GVHD.…”

“…Intentional cGVHD or a GVL effect is needed in specific clinical situations where standard allogeneic transplantation by itself does not lead to good survival, such as high-risk ALL (pre-B ALL or Philadelphia chromosome positive ALL), primary refractory leukemia, or CML in blastic crisis. 23 Brunet et al 10 suggested that the use of allogeneic PBSC, which contains 2-4 times more CD34+ cells than bone marrow, may be preferable in advanced hematological malignancies as the source of stem cells. Based on the current study, for patients with a high risk of relapse, transplantation with a CD34+ cell dose of 410.5 Â 10 6 /kg would appear to be acceptable to minimize the relapse risk by inducing a potent graft-versus-disease effect.…”