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The Transplant Centers belonging to Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO) conducted a survey with the aim of evaluating the effect of SARS-CoV2 pandemic on the allogeneic transplant activity in Italy. The pandemic period from 1/3/2020 to 31/7/2020 was compared with the same period in 2019. Overall, in 2020 there was a 2.4% reduction in the number of allo-HCT cases compared to 2019. Interestingly, this deflection did not affect the acute leukemia cases (+5.7% in 2020). The use of peripheral blood-derived stem cells (+10.7%) and cryopreservation (97.4% of the centers) was highly adopted in 2020. Despite the sanitary emergency, almost all of the surveyed centers declared no impact of SARS-CoV2 pandemic on the transplant timing and outcomes, and the sanitary policy was positively evaluated by the majority of centers. The emergency measures ensured that only a minority of the allo-HCT patients had been infected by SARS-CoV2; however, a mortality of 42.1% among the allo-HCT patients hospitalized for COVID-19 was recorded. This survey gives us the information that the GITMO Group reacted positively to the pandemic. Thanks to the emergency strategies, the Italian allo-HCT activity continued safely, showing only a minor deflection and offering the same probability of cure to the transplanted patients.

What is known and objective The aim of this survey, conducted by the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), was to evaluate the involvement of pharmacists in the haematopoietic stem cell transplant (HSCT) program in Italian adult and paediatric centres. Methods A 63-item online questionnaire was developed and sent to the Italian Transplant Programs on behalf of GITMO. Results and discussion Overall, 54.7% of the Italian HSCT centres participated in the survey (88.5% adult, 7.7% paediatric, 3.8% mixed), of which 50% were in public hospitals and 50% affiliated with public universities. Just over 80% declared that a pharmacist is involved in the HSCT centre, and 86.5% reported the presence of a documentation system to signal of adverse events, accessible by physicians, nurses and pharmacists in 57.7%. Chemotherapy drugs were centralized in the pharmacy in 98.1% of HSCT centres, while parenteral nutrition was centralized in 55.8%. The use of off-label drugs was authorized by an internal committee and by the regional health authorities in 88.5% of the centres. On univariate analysis, few statistically significant differences were found on response frequencies between public hospitals and university centres or between HSCT centres performing only autologous stem cell transplantation versus other centres performing autologous and allogeneic stem cell transplantation. What is new and conclusion This survey suggests that there is good collaboration between pharmacists and physicians and nurses in Italian HSCT transplantation centres. The enhancement of pharmacists dedicated to HSCT programs could improve some problems, for example, the centralization of parenteral nutrition.

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and. 007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and. 01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence.

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%).

Haemorrhagic cystitis (HC) is a recognised complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). This study evaluates the incidence and severity of HC in patients undergoing allogeneic HSCT during hospitalisation and within the first 100 days following transplant, looking at the use of prophylaxis, management of HC, outcomes at 100 days post transplant, and to identify any correlations between development of HC and the different conditioning regimens for transplant or HC prevention methods used. Results Four hundred and fifty patients (412 adult and 38 paediatric) were enrolled in this prospective, multicentre, and observational study. HC was observed in 55 patients (12.2%) of which 8/38 were paediatric (21% of total paediatric sample) and 47/412 adults (11.4% of total adult sample). HC was observed primarily in the non-related HSCT group (45/55; 81.8%, p= 0.001) compared to sibling and myeloablative transplant protocols (48/55; 87.3%; p= 0.008) and with respect to reduced intensity conditioning regimens (7/55;12.7%). In 33 patients with HC (60%), BK virus was isolated in urine samples, a potential co-factor in the pathogenesis of HC. The median day of HC presentation was 23 days post HSCT infusion, with a mean duration of 20 days. The most frequent therapeutic treatments were placement of a bladder catheter (31/55; 56%) and continuous bladder irrigation (40/55; 73%). The range of variables in terms of conditioning regimens and so on, makes analysis difficult. Conclusions This multi-centre national study reported similar incidence rates of HC to those in the literature. Evidence-based guidelines for prophylaxis and management are required in transplant centres. Further research is required to look at both prophylactic and therapeutic interventions, which also consider toxicity of newer conditioning regimens.