Haploidentical allogeneic hematopoietic stem cell transplantation increases the risk of cytomegalovirus infection in adult patients with acute leukemia

Abstract

Background:Owing to the shortage of hematopoietic stem cells from matched sibling donors (MSD) and matched unrelated donors (MUD), the number of patients undergoing haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) has rapidly increased. Despite a comparable overall survival (OS) and leukemia-free survival using this approach, some evidence suggests that haploidentical allo-HSCT recipients have a higher incidence of cytomegalovirus (CMV) infection, though this has not been clearly established. Methods:This study retrospectively compared the cumulative incidence of CMV DNAemia, 2-year OS, and leukemia-free survival rates in acute leukemia patients with MSD (n = 41), MUD (n = 18), and haploidentical donor allografts (n = 21). Results:The cumulative incidences of CMV DNAemia at day 180 in the MSD, MUD, and haploidentical groups were 39.0, 55.6, and 85.7%, respectively (P < 0.000). As less than 50% of patients in the MSD group were detected to have CMV DNAemia, the median time to CMV DNAemia detection in patients allografted with MSD could not be obtained. However, it was 42 and 29 days, respectively, for the MUD and haploidentical groups. Multivariate analysis revealed that haploidentical allo-HSCT (MSD vs. haploidentical: HR: 0.26; 95% CI: 0.09-0.78; P = 0.017) and age (HR: 1.03; 95% CI: 1.01-1.06; P = 0.011) increased CMV infection. Finally, MSD, MUD, and haploidentical allo-HSCT provided comparable 2-year OS rates (52.1%, 65.5%, and 65.6%; P = 0.425) and 2-year leukemia-free survival rates (67.1%, 68.3%, and 80.7%, P = 0.837). Conclusion:The CMV incidence was higher for haploidentical allo-HSCT than for MSD and MUD allo-HSCT; this could be explained by graft-versus-host disease prophylaxis by multiple immunosuppressants. K E Y W O R D Sallo-HSCT, haploidentical, cytomegalovirus, overall survival, leukemia-free survival

Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post‐transplantation cyclophosphamide

“…The above observation could be explained, at least in part, by the delay in CD4 + T‐cell reconstitution apparently experienced by patients undergoing haplo‐HSCT, in comparison with HLA‐matched allo‐HSCTs . This might also account for the increased incidence of CMV disease seemingly occurring in our cohort and reported by other groups and the high rate of CMV drug resistance among patients receiving PET after haplo‐HSCT, presumably linked to persistent viral replication . In the absence of data on CMV‐specific T‐cell immunity, this is nevertheless merely speculative, yet our data suggest that OM and NRM in patients undergoing haplo‐HSCT by days 180 and 365 are not different from that in patients subjected to other allo‐HSCT types, as has been previously reported …”

“…Regarding the latter issue, the cumulative incidence of CMV DNAemia was lower at HCUS (48.4%), where the Affigene Trender CMV PCR kit was used, than at the other participating centers (ranging from 56% to 78%), in which a more sensitive PCR assay (Abbott) was employed. Notwithstanding, these figures are substantially lower than those reported for haplo‐HSCT with combined used of cyclophosphamide and ATG, which could be as high as 87% …”

“…Notwithstanding, these figures are substantially lower than those reported for haplo-HSCT with combined used of cyclophosphamide and ATG, which could be as high as 87%. 15,20 In our haplo-HSCT cohort only recipient CMV seropositivity was associated with an increased risk of CMV DNAemia. Use of highdose corticosteroids for severe aGvHD, 14 or conditioning regimens containing myeloablative doses of busulfan, 19 or preceding HHV-6…”

“…Occurrence of CMV disease in patients undergoing haplo-HSCT with or without T-cell depletion has been consistently reported as high, ranging from 11% to 17%, [12][13][14][15] compared with those in other allo-HSCT modalities (less than 10%). 6 In a recent survey across Spanish centers performing all types of allo-HSCTs in adult patients the cumulative incidence of CMV disease was 2.8%.…”

“…[1][2][3][4][5] Cytomegalovirus (CMV) remains a threat for allo-HSCT recipients despite the availability of effective strategies for the prevention of end-organ disease (ie, preemptive therapy), 6 since viral DNAemia itself may be detrimental in terms of survival. [7][8][9][10][11] Conflicting data have been published as to the incidence of CMV DNAemia and CMV disease in haplo-HSCT recipients, with some studies suggesting that this transplant modality harbors a significantly higher risk for both events when compared to HLA-matched related or unrelated allo-HSCTs, [12][13][14][15][16][17][18][19][20][21][22] yet this appeared not to have an impact on overall (OM) and non-relapse (NRM) mortality. 18,[23][24][25] In the current multicenter study, we estimated the incidence of CMV DNAemia, CMV disease OM, and NRM in haplo-allo-HSCT and compared to that in other transplant modalities.…”