Severe Infections after Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation in Adults: Comparison of Cord Blood Transplantation with Peripheral Blood and Bone Marrow Transplantation

Abstract

We evaluated the occurrence of severe infections in 192 consecutive adult recipients of volunteer unrelated donor allogeneic hematopoietic stem cell transplants, with a detailed analysis of severe infections after receipt of cord blood transplants (CBTs; n = 48) or bone marrow transplants (BMTs)/peripheral blood stem cell transplants (PBSCTs; n = 144). At a 3-year median follow-up, CBT recipients had a higher risk of developing any severe infection (85% versus 69% in BMT/PBSCT recipients, P < .01). CBT recipients had a higher incidence of severe bacterial infections before day +100, but at 3 years the risks of these and other infections were similar in the CBT and BMT/PBSCT groups. In addition, the 100-day and 3-year incidences of infection-related mortality (IRM) did not differ between groups (P = .2 and .5, respectively). In multivariate analysis, the most significant risk factor for IRM in all 192 patients was monocytopenia (.2 x 10(9)/L). In CBT recipients, only neutropenia (.2 x 10(9)/L) on day +30 and low nucleated cell dose infusion (< 2 x 10(7)/kg) showed a trend for increased IRM (P = .05 in both cases). Stem cell source had no effect on day +100 or 3-year nonrelapse mortality (NRM), cytomegalovirus infection, cytomegalovirus disease (7% versus 6%), or overall survival (36% versus 39%, respectively). The number of mismatches in HLA (A, B, and DRB1) had no effect on any outcome in CBT recipients. In contrast, in the BMT/PBSCT group, the presence of any mismatch by low or high-resolution HLA typing (A, B, C, and DRB1) increased NRM and decreased overall survival (P < .01). IRM was the primary or secondary cause of death in 61% and 59% of CBT and BMT/PBSCT recipients who died, respectively. Our results confirm the relevance of severe infectious complications as source of severe morbidity and NRM after volunteer unrelated donor hematopoietic stem cell transplantation in adults, but suggest that CBT recipients have a similar risk of dying from an infection if an accurate selection of a cord blood unit is done.

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

“…CBT is now routinely utilized for the treatment of both adult [2][3][4][5] and pediatric 6 patients with hematological diseases, with similar reported outcomes as compared with hematopoietic SCT (HSCT) in which either adult BM or peripheral blood was used as a source of stem cells (non-CB HSCT). [7][8][9] Many human herpesviruses (HHVs) can be reactivated following HSCT, and have been associated with adverse outcomes in this clinical setting.…”

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

“…For instance, some investigators described a similar incidence of CMV reactivation after CBT and allo-SCT transplantation using peripheral blood or BM SC. 3,6 In contrast, human herpes virus 6 (HHV6) reactivations appear to occur more frequently after CBT both in children 9 and in adults. 10,11 This report aimed to analyze the incidence, features and outcome of CMV, EBV and HHV6 infections in 55 consecutive adult patients receiving unrelated CBT or allo-HSCT from HLA-matched unrelated donors (MUD).…”

“…5 However, despite these initial encouraging results, opportunistic infections remain a matter of concern after cord blood transplantation (CBT) as a consequence of delayed hematopoietic and immune reconstitution. [1][2][3][4]6 Indeed, different studies documented a higher incidence of severe bacterial infections accountable for early mortality in adult patients receiving CBT. 3,7,8 Data related to viral infections after CBT (especially for Herpesviridae) are still relatively scarce.…”

“…[1][2][3][4]6 Indeed, different studies documented a higher incidence of severe bacterial infections accountable for early mortality in adult patients receiving CBT. 3,7,8 Data related to viral infections after CBT (especially for Herpesviridae) are still relatively scarce. For instance, some investigators described a similar incidence of CMV reactivation after CBT and allo-SCT transplantation using peripheral blood or BM SC.…”

“…Cord blood as a stem cell (SC) source is increasingly accepted as an alternative source of hematopoietic SCs for allogeneic SCT (allo-HSCT) in adult patients with hematological diseases, both in the myeloablative [1][2][3][4] and the reduced-intensity conditioning settings. 5 However, despite these initial encouraging results, opportunistic infections remain a matter of concern after cord blood transplantation (CBT) as a consequence of delayed hematopoietic and immune reconstitution.…”