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We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past 20 years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation +/- fludarabine or clofarabine before transplantation from HLAmatched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor +/- sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997-2003 (n=562), 2004-2009 (n =594), and 2010-2017 (n=564). The proportion of patients >= 60 years old increased from 27% in 1997-2003 to 56% in 2010-2017, and with scores from the Hematopoietic Cell Transplantation Comorbidity Index of >= 3 increased from 25% in 1997-2003 to 45% in 2010-2017. Use of unrelated donors increased from 34% in 1997-2003 to 65% in 2010-2017. When outcomes from 2004-2009 and 2010-2017 were compared to 1997-2003, improvements were noted in overall survival (P=0.0001 for 2004-2009 and P <= 0.0001 for 2010-2017), progression-free survival (P=0.002 for 2004-2009 and P<0.0001 for 2010-2017), non-relapse mortality (P<0.0001 for 20042009 and P<0.0001 for 2010-2017), and in rates of grades 2-4 acute and chronic graft-versus-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades.

Objectives Vitamin E has antioxidant and immunomodulatory effects that might influence the development of acute graft-versus-host disease (GvHD). We investigated the association between plasma vitamin E levels and acute GvHD.Methods We studied 115 adults who underwent myeloablative allogeneic hematopoietic cell transplantation between July 2015 and August 2018. Vitamin E was measured by high-performance liquid chromatography in stored plasma samples obtained pre-transplantation at day -23 (+/- 15 days) and post-transplantation at day +28 (+/- 3 days).Results Pre-transplantation vitamin E levels were inversely associated with grade II-IV acute GvHD (hazard ratio 0.68 per 10 mu mol/L increase, 95% confidence interval [CI]: 0.47-0.98). The association remained after adjustment for known prognostic factors for acute GvHD. Patients with levels below the median had a cumulative incidence of grade II-IV acute GvHD of 46% (CI: 33-59%) versus 21% (CI: 10-32%) in patients with levels above the median. No clear association with non-relapse mortality, relapse, or chronic GvHD was found. Post-transplantation vitamin E levels (measured in 72 [63%] patients) were correlated with pre-transplantation levels (rho = .31) but were not associated with subsequent grade II-IV acute GvHD.Conclusions High pre-transplantation vitamin E levels were associated with less acute GvHD.

Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.