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. 2016 Feb;22(2):359-370.
doi: 10.1016/j.bbmt.2015.09.013. Epub 2015 Sep 25.

Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors

Jo-Anne H Young  1 , Brent R Logan  2 , Juan Wu  3 , John R Wingard  4 , Daniel J Weisdorf  5 , Cathryn Mudrick  3 , Kristin Knust  3 , Mary M Horowitz  2 , Dennis L Confer  6 , Erik R Dubberke  7 , Steven A Pergam  8 , Francisco M Marty  9 , Lynne M Strasfeld  10 , Janice Wes M Brown  11 , Amelia A Langston  12 , Mindy G Schuster  13 , Daniel R Kaul  14 , Stanley I Martin  15 , Claudio Anasetti  16 ; Blood and Marrow Transplant Clinical Trials Network Trial 0201
Affiliations

Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors

Jo-Anne H Young et al. Biol Blood Marrow Transplant. 2016 Feb.

Abstract

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.

Keywords: Aspergillosis; Bacteremia; Cytomegalovirus; Infection; Pre-engraftment; Unrelated donor transplantation.

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Conflict of interest statement

Disclosure of potential conflicts of interest

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Descriptive Analysis of Infection Severity
Infection Severity by Treatment Arm. (A) All infection events. (B) Maximum severity of infections (p = 0.6).
Figure 2
Figure 2
Cumulative Incidence of All Infections
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 3
Figure 3
Cumulative Incidence of Specific Infections. (A) Bacteria from all sites. (B) Bloodstream bacteria. (C) All viruses. (D) Cytomegalovirus. (E) All Fungal/Parasitic Infections. (F) Aspergillus infections.
Figure 4
Figure 4
Infection Density for each time period. (A) Total infection density. (B) Bacterial infection. (C) Viral infection. (D) Fungal infection. (E) Bloodstream bacterial infection. (F) Non-bloodstream bacterial infection. (G) Moderate infection. (H) Severe infection. (I) Life-threatening infection.
Figure 5
Figure 5
Relationship of Infection to Engraftment. (A) Cumulative incidence of infections that occurred among engrafted patients. (B) Cumulative incidence of pre-engraftment infections.
Figure 5
Figure 5
Relationship of Infection to Engraftment. (A) Cumulative incidence of infections that occurred among engrafted patients. (B) Cumulative incidence of pre-engraftment infections.
See this image and copyright information in PMC

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