The influence of infection early after allogeneic stem cell transplantation on the risk of leukemic relapse and graft‐versus‐host disease

Abstract

An infection after allogeneic stem cell transplantation (SCT) can affect the activity of immune cells and increase the level of proinflammatory cytokines. Further, a post-SCT infection may influence the milieu of the graft-versus-leukemia (GVL) effect and graft-versus-host disease (GVHD). We performed a retrospective study of patients with acute leukemia who had undergone allogeneic SCT using the same preparative regimens and bone marrow as the stem cell source to determine if early post-transplant infection was associated with the risk of leukemic relapse and GVHD. The analysis revealed that patients who had a febrile infection (FI) before post-transplant day 21 (FI group) had a lower actuarial probability of leukemic relapse (P < 0.001) and a higher relapse-free survival rate (P 5 0.012) than those patients who did not have a FI before post-transplant day 21 (non-FI group). The experience of early post-transplant FI (HR 5 0.316; 95% CI 5 0.174-0.575; P < 0.001), together with the presence of chronic GVHD and high risk cytogenetics, were independent predictive factors for post-transplant leukemic relapse. The FI group had a trend towards a higher lymphocyte count on post-transplant day 21 than the non-FI group (P 5 0.063), despite the delayed recovery of the platelet count and a trend towards delayed recovery of the neutrophil count. These findings suggest that a change in the immunologic network by infectious diseases in the early post-transplant period favors the milieu of the GVL effect. The specific immunologic change during FI, which can potentiate the GVL effect, remains to be determined. Am. J. Hematol. 83:784-788, 2008. V V C 2008 Wiley-Liss, Inc. IntroductionThe graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) is an important means by which residual hematologic malignant cells surviving pretransplant chemoradiation are eradicated. The GVL effect is mediated by a complex network of immune cells and cytokines [1][2][3]. As inflammatory events following allogeneic SCT can change the activity of the host and donor graft immune cells that release various inflammatory cytokines [4][5][6], post-transplant infection may influence the milieu of the GVL effect and, accordingly, the risk of posttransplant leukemic relapse.Post-transplant infections usually occur early after transplantation and the activation of host antigen-presenting cells and donor NK cells has been shown to occur quite early in both experimental and human allogeneic SCT [7,8]. We investigated whether a febrile infection (FI) before posttransplant day 21 was associated with a risk of leukemic relapse and graft-versus-host disease (GVHD) in patients with acute leukemia. To avoid confounding factors potentially affecting immune reconstitution after allogeneic SCT and evaluate the association between the GVL effect and the variables evaluated, we restricted the study population to 215 consecutive patients with acute leukemia who had undergone allogeneic SCT using the same preparative regimens and bone marrow as the ...

Early Lymphocyte Recovery and Outcomes after Umbilical Cord Blood Transplantation (UCBT) for Hematologic Malignancies

“…The early increases in T cells after transplant are thought to be mainly due to homeostatic T cell proliferation, where a limited repertoire of T cells emerge in response to alloantigen stimulation and high serum cytokine concentrations. Whether these T cells are protective against relapse or infectious organisms remains an open question in humans, but both have been hypothesized (32–33). Perhaps in support of this, Hamza et al showed that patients with rapid lymphoid recovery after UCBT and MUD BMT had a lower risk of infections (12).…”

Intestinal Damage Determines the Inflammatory Response and Early Complications in Patients Receiving Conditioning for a Stem Cell Transplantation

“…Other studies have shown that infections may contribute to non-infectious complications including acute GvHD [10], [11]. However, few if any of these studies addressed the role of MBI per se as an isolated cause of inflammation and risk factor for infections, nor its role in the pathogenesis of inflammatory complications.…”

The Impact of Early Viral Infections and Graft‐Versus‐Host Disease on Immune Reconstitution Following Paediatric Stem Cell Transplantation

“…The prevalence of post-transplant infections appears linked to the intensity of immunosuppression and the drugs employed [18] putatively through their impact on T cell number and function. Early viral infections may also have a direct effect on immune recovery after HSCT [19]. Furthermore, their incidence and treatment appear linked to the degree of immunosuppression and the pace of immune reconstitution following transplant.…”