A reply to the questionnaire was received from 180 of the 579 mailed centres (31%). The responding centres were from all 5 continents, but prevalently from Europe, and included 40 countries (table S1). Among them, 104 (58%) were centres only for adult patients, 43 (24%) were centres only for paediatric patients, and 33 (18%) were centres with a joined adult and paediatric transplant program. In this last group, the same approach both for adult and paediatric patients for management of CMV infection was declared by 22 of 33 (67%) centres.

Overall, the responding centres performed in 2019 a median of 40 transplant procedures per centre (range 1- 247), with the median of 62 transplants (range 1-146) for adult/paediatric centres, of 43 transplants (range 5-247) for adult centres, and of 24 transplants (range 1-106) for paediatric centres. All centres performed both related and unrelated HCT. The main results of the survey are showed in Table 1.

CMV surveillance: 175 of 180 centres (97%) used PCR for CMV monitoring, 4 centres (2%) used serum pp65 antigenemia, and 1 centre used both PCR and pp65. Quantitative PCR was adopted in 173 of 175 centres (99%; 2 centres missing) using blood (122, 70%), plasma (44, 25%) or serum (6, 3%) while for 3 centres (2%) the data were missing. The quantitation of CMV load was expressed as CMV genomic copies/ml in 116 (66%), international unit/ml (IU) in 51 (29%), and both measures in 4 (2%) centres, respectively, while data were missing for 4 centres (2%). In 80 centres (44%), the determination of CMV-DNAemia in blood or plasma was also part of the pre-transplant work-up assessment.

CMV monitoring was performed for all types of allogeneic (allo)-HCT in 171 centres (95%), while in 7 centres (4%) CMV monitoring was limited to allo-HCT considered at higher risk of CMV infection such as unrelated HCT, related and unrelated cord blood (CB) HCT, T-cell replete or T-cell ex-vivo depleted haploidentical HCT, and positive CMV serology of the recipient or of the donor.

During the first 100 days post-allo-HCT, the frequency of surveillance was 1 time/week in 109 (61%), 2 times/week in 53 (29%), 2 times/week during the hospitalization for transplant followed by once a week after hospital discharge in 8 (4%), while the frequency was modulated according to immune recovery or recipient/donor CMV positivity in 4 centres (2%) and data were missing in 6 (3%).

The duration of CMV surveillance was reported as fixed until day +100 in 8 (4%) of centres while it was extended beyond day + 100 according the presence of the following criteria: active treatment for GVHD or immunosuppressive therapy or steroid therapy in 147 (82%), CD4 + count <0.25 × 109/L in 7 (4%), lymphocyte count <0.3 × 109/L) in 8 (4%), at least 6 months post-HCT in 3 (2%); data were missing for 7 centres (4%).

CMV prophylaxis: in high-risk patients (CMV seropositivity in the recipient or in the donor), drug prophylaxis was used in 101 (56%) with a higher prevalence in adult and adult/paediatric than paediatric centres (62% and 61% vs. 37%, p 0.002). The drugs used were: letermovir in 62 centres (61%), aciclovir/valaciclovir in 19 centres (19%), ganciclovir/valganciclovir in 17 centres (17%), foscarnet in 3 centres (3%). Among 62 centres that declared to use letermovir prophylaxis, 48 (77%) were adult HCT centres, 13 (21%) joined adult and paediatric centres and 1 (2%) paediatric centre; moreover, in the 13 centres with a joined adult and paediatric transplant program, 7 declared to adopt a common approach for CMV management both for adult and paediatric patients.

In addition to drug prophylaxis, the use of CMV-hyperimmune globulins and CMV cytotoxic T-lymphocytes (CMV-CTLs) in this setting were reported in 4 (4%) and 2 (2%) centres, respectively.

CMV infection and preemptive treatment: the median number of estimated preemptive treatments/years for CMV infection was 12 per centre (range 1-50).

The information on the drug used as first line preemptive therapy for unmanipulated allo-HCT were available for 175 centres: ganciclovir/valganciclovir in 168 centres (93%), foscarnet in 7 centres (4%); data were missing for 5 centres (3%). In addition to preemptive therapy, the use of CMV-hyperimmune globulins and CMV-CTLs in this setting were reported in 6 (3%) and 1 (1%) centre, respectively.

Considering ex-vivo T-cell depleted graft, the information on the first-line preemptive therapy was available for 119 centres: ganciclovir/valganciclovir in 111 centres (93%), foscarnet in 7 centres (6%), cidofovir in 1 centre (1%) while the data were missing in 61 centres (34%). CMV-hyperimmune globulins and CMV-CTLs were used together with preemptive drug therapy in 5 (3%) and 2 (1%) centres, respectively.

Table 2 shows the threshold used to start pre-emptive therapy in patients monitored with PCR for CMV and received an unmanipulated or an ex-vivo manipulated graft, respectively. A threshold >103 of copies/ml or IU/ml was the most used trigger to start preemptive therapy both in unmanipulated and in manipulated (ex-vivo T-depletion) grafts.

The criteria to establish the duration of pre-emptive treatment both for T-repleted and T-depleted allo-HCT was specified by 173 centres (96%), as follows: at least 2 weeks in 4 (2%), 2 consecutive CMV-DNAemia negative results in 138 (77%), until CMV-DNAemia gets down the threshold used to start treatment in 26 (14%), and until an adequate immune recovery is achieved in 5 (3%), not specified or missing in 7 (4%).

CMV disease and treatment: during the year 2019, 116 of 180 centres (64%) reported to have diagnosed ≥ 1 episode of CMV disease (median 2, range 1-50) for a total of 605 episodes. The episodes of CMV disease were classified as proven in 217 (36%), probable in 183 (30%) and possible in 205 (34%) while no information was given for the remaining 185 episodes.

The first-line treatment for CMV disease in unmanipulated allo-HCT was reported by 167 of 180 centres (93%): ganciclovir/valganciclovir in 158 (88%), foscarnet in 9 (5%), while data were missing for 13 centres (7%). CMV-hyperimmune globulin and CMV-CTLs were used in combination with drug therapy in 13 centres (7%) and 2 (1%). In manipulated HCT, the first-line therapy was reported in 113 centres (63%): ganciclovir/valganciclovir in 104 centres (92%) foscarnet in 8 (7%), cidofovir in 1 centre (1%) CMV-hyperimmune globulin and CMV-CTLs were used in combination with drug therapy in 10 (9%) and 4 (4%) centres, respectively.

The duration of therapy for CMV disease was reported by 163 centres (91%) and resulted as follows: until clinical resolution of clinical symptoms and two consecutive CMV-DNAemia negative results in 124 (69%), until clinical resolution of symptoms and CMV-DNAemia gets down the threshold used to start treatment in 25 (14%), until an adequate immune recovery is achieved in 3 (2%), until 3-6 weeks of treatment is completed in 11 (6%), not specified or missing in 17 (9%).

Fifty centres (28%) declared also to use CMV-CTLs mainly in the context of the treatment of refractory or recurrent CMV disease or clinical trial. Lastly, in 48 of 180 centres (27%) a median of 2 (range 1-12) cases of CMV resistance (infection or disease) were reported.