Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients

Summary:Transplant-related mortality (TRM) following allogeneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin Ͻ0.9 and/or BUN Ͻ21) and 93 patients with score 2 (high risk) (bilirubin у0.9 and BUN у21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs 44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs 35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P Ͻ 0.01), after adjustment for year of transplant (P Ͻ 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be Allogeneic bone marrow transplantation (BMT) is associated with considerable morbidity and mortality, and several studies have addressed the issue of risk factors for major single complications such as interstitial pneumonitis, 1 acute GVHD 2,3 and graft rejection: 4 patient variables (older age), donor variables (older age, parous female donors for male recipients, degree of HLA matching) and transplant variables (longer interval from diagnosis to transplant, intensive regimens), are among these. A study from the Seattle group has looked at risk factors for veno-occlusive disease of the liver, another important complication of allogeneic BMT 5 and found that early increments in serum bilirubin level and body weight were highly predictive. Other studies have also addressed the impact of risk factors on post-BMT complications. [6][7][8][9][10] During the past decades we have improved our ability to prevent and/or treat such complications, and transplantrelated mortality (TRM) has been considerably reduced 11 and delayed: in our HLA-identical sibling program TRM was 39% before 1990 (385 patients) and occurred at a...

Section: Discussionmentioning

confidence: 99%

Section: Data Collectionmentioning

confidence: 99%

Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin

Bacigalupo

Oneto

Bruno

et al. 1999

“…[1][2][3] The introduction of reduced intensity conditioning regimens, peripheral blood stem cells and newer antifungal agents have not appeared to decrease the risk of late IA. [4][5][6] Current antifungal prophylactic strategies have had little effect on the incidence of IA 7,8 and once the diagnosis is made, survival is universally poor.…”

mentioning

confidence: 99%

Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation

Thursky

Byrnes

Grigg

et al. 2004

Summary:The majority of invasive aspergillosis (IA) in allogeneic stem cell transplantation (SCT) occurs during the postengraftment period. We used Cox proportional hazards regression to evaluate post-engraftment IA risk in a cohort of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the effects of dose-intensity and duration of corticosteroids and other risk factors. Median duration of follow-up was 330 days. There were 19 cases of IA (overall 8.8%) with 14 post-engraftment infections. In the final model, the risk of IA was greatest within 2 weeks of high-dose corticosteroids (HR 8.5, P ¼ 0.003), with risk extending to 4 weeks with doses of 0.25-1 mg/kg/day (HR 3.1, P ¼ 0.08). Ganciclovir was associated with greatest risk (HR 13.6). Grade 3 or 4 acute GVHD (HR 5.7) and secondary neutropenia (HR ¼ 1.3) were also additive risks. In the univariate analysis, corticosteroid doses of 0.25-1.0 mg/kg/day for any duration between 2 and 10 weeks demonstrated prolonged risk for IA. Moderate doses of corticosteroids can confer an increased risk for IA for extended periods which is almost as marked as that conferred by higher doses. Knowledge of these risks may facilitate the development of targeted surveillance and prophylaxis strategies for prevention of IA.

“…20 The contribution of neutropenia to invasive fungal infections is an approximately 15% incidence after therapy of acute leukaemia or marrow transplantation. 21,22 Most aspergillus infections in allo-SCT recipients occur late after transplantation and are associated with acute or chronic GVHD and its treatment with immunosuppressives. 7,22 In our study MU/MM allo-SCT recipients received more, but not significantly so, empirical intravenous amphotericin B than did patients who had undergone MR allo-SCT.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

“…21,22 Most aspergillus infections in allo-SCT recipients occur late after transplantation and are associated with acute or chronic GVHD and its treatment with immunosuppressives. 7,22 In our study MU/MM allo-SCT recipients received more, but not significantly so, empirical intravenous amphotericin B than did patients who had undergone MR allo-SCT. Also, early aspergillus infections were not associated with transplant type.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

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

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.