Early Infection in Bone Marrow Transplantation: Quantitative Study of Clinical Factors That Affect Risk

Summary:We compared the incidence of early infectious complications between matched related (MR) and matched unrelated/mismatched (MU/MM) allogeneic stem cell transplant (allo-SCT) recipients in a single centre over a 6-year period in 214 consecutive adult patients. Early infections were defined as occurring from hospital admission for SCT until discharge. One hundred and fifty-nine patients received an allograft from MR donors and 55 patients received MU/MM allo-SCT. One hundred and eight of 214 patients had 147 episodes of fever. Ninety-three episodes (63%) were due to clinically or microbiologically documented infections and 54 episodes (37%) to fever not related to infection. Patients undergoing MU/MM transplantation tended to have more documented infections compared to recipients of MR allo-SCT (P = 0.06). Significantly more MU/MM transplant recipients had breakthrough infections with Herpes simplex virus type 1 (HSV-1, P = 0.003), and more CMV reactivation (P = 0.015). The mortality rate in all patients during hospitalisation post-SCT was 6.3% in MR and 18.2% in MU/MM allo-SCT recipients (P = 0.009). Early mortality was associated with infection in 70% of the patients, with a similar distribution between MR and MU/MM transplant recipients. However, MU/MM transplant recipients had significantly more early deaths due to toxic causes (P Ͻ 0.001). We conclude that early post-transplant MU/MM transplant recipients tend to have more documented infections, and have significantly more breakthrough infections with HSV-1 and more CMV reactivation. MU/MM transplant recipients are at higher risk of early mortality, especially due to toxic causes.

Section: Bone Marrow Transplantationsupporting

confidence: 47%

Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence

Kraaij

Verdonck

Rozenberg-Arska

et al. 2002

“…We and others have shown that antimicrobial prophylaxis is associated with reduced mortality after HSCT. 3 However, other strategies of preventing BSI after HSCT, such as reducing BSI from gut-derived pathogens like GNR or vancomycin-resistant Enterococcus, deserves further study.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 It has been observed to occur in 13-60% of HSCT recipients. 1,[3][4][5][6][7][8][9][10] The differences in findings of these studies is likely due to factors such as different study designs, study populations, conditioning regimens and prophylactic antibiotic protocols. However, essentially all of the studies cited demonstrated that Gram-positive organisms, particularly coagulase-negative staphylococci and viridans group streptococci, were responsible for most BSI after HSCT.…”

Section: Introductionmentioning

confidence: 99%

Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality

Poutsiaka

Price

Ucuzian

et al. 2007

181

149

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P ¼ 0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P ¼ 0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P ¼ 0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death p3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.

“…[1][2][3][4][5][6][7] This reduced extrahematologic toxicity may lead to a reduction in infectious complications post transplant, since disruption of the gastrointestinal mucosa and/or damage to other key organs is a significant triggering mechanism of many of the infections that occur post transplant. 8,9 On the other hand, graft-versus-host disease (GVHD) and its treatment has a profound negative impact on immune reconstitution following HSCT, 10 and the impact of RIC regimens on the risk of acute and chronic GVHD is currently uncertain. The potential benefit on the risk of early infections derived from reduction of the intensity of the conditioning regimen may be negated by the immunodeficiency resulting from GVHD and its therapies.…”

Section: Discussionmentioning

confidence: 99%

Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation

Martino

Caballero

Canals

et al. 2001

Summary:We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P Ͻ 0.001) and a dose of CD34 + cells infused below 6 × 10 6 /kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an Following conventional allogeneic hematopoietic stem cell transplantation (HSCT) all patients experience a period of profound neutropenia and immunodeficiency that are significantly responsible for the serious infectious complications that ensue post transplant. Standard conditioning regimens for HSCT involve high-dose chemoradiotherapy given in doses that are myeloablative or at least severely myelotoxic. However, over the past years several groups of investigators have developed reduced-intensity conditioning (RIC) or non-myeloablative regimens, which lead to engraftment of donor lymphoid and hematopoietic stem cells without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6][7] This reduced extrahematologic toxicity may lead to a reduction in infectious complications post transplant, since disruption of the gastrointestinal mucosa and/or damage to other key organs is a significant triggering mechanism of many of the infections that occur post transplant. 8,9 On the other hand, graft-versus-host disease (GVHD) and its treatment has a profound negative impact on immune reconstitution following HSCT, 10 and the impact of RIC regimens on the risk of acute and chronic GVHD is currently uncertain. The potential benefit on the ri...