Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching

Abstract

Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced 1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade 2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.

Severe infections and infection-related mortality in a large series of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

“…In our series, the 3-year incidence of GPB and GNB infections was 51% and 46%, respectively (246 episodes), similar to the incidence reported by others which range from 35% to 62% [ 27 – 30 ], albeit somewhat different definitions were used in different studies. The rates of GPB infections were similar in the pre-engraftment and late post-engraftment period, while GNB infections were more common in the late post-engraftment period (> day +100).…”

Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching

“…Regarding viral infections, their incidence was high in early post-engraftment phase and more frequent in haploSCT recipients. Both CMV-I and viral HC were especially high in haploSCT recipients between days +30 to +90 post transplant, with incidences of 45% and 27%, respectively, comparable to other haploSCT studies [ 32 , 40 , 53 , 54 ]. Beyond day +100 rates of CMV and HC infection were similar between the different stem cell donor groups.…”

“…Overall, this is a positive observation since PTCy could potentially increase the mucosal barrier injury-linked infections due to more intense and prolonged damage to the gastro-intestinal mucosa combined with a more prolonged duration of neutropenia and monocytopenia, leading to a higher pre-engraftment (before day +30) IRM [ 38 – 40 ]. With respect to post-engraftment infections, there was a low incidence of late bacterial infections (24% of evaluable cases), probably explained by the low incidence of severe forms of both acute and chronic GvHD.…”

“…Prior studies have reported an incidence of IRM of 9% to 20% in patients receiving PTCy-based alloSCT platforms [ 30 , 32 , 40 ], although most studies have focused on haploSCT since this has been the most common setting for the use of PTCy. Our finding of a 9% IRM at 18 months, without differences between haploSCT and MRS/VUD/MMUD is thus promising.…”

Allogeneic bone marrow transplantation in HIV people with hematological malignancies: Post‐transplant cyclophosphamide to overcome the HLA‐matching barrier

“…Regarding ART, 1/5 switched from triple therapy non-nucleoside All patients experienced at least one double-strand DNA viral infection (Cytomegalovirus, Adenovirus, Human herpes virus 6); we do not attribute this finding to a higher risk of immunosuppression in PLWH after transplant, having reported in a cohort of HIV negative BMT recipients with PT-Cy platform an incidence of double-strand DNA viral infection of 91% at 90-days. 8 In our cohort, non-relapse mortality at 100-days was 0%; all patients are alive in complete remission at a median follow-up of 34 months (IQR: 10.5-52). Two patients developed GVHD and the immunosuppressant therapy did not affect plasmatic HIV replication.…”