Publications by authors named "Elisabetta Xue"

10 Publications

  • Page 1 of 1

Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience.

Leuk Res 2021 Jun 11;109:106642. Epub 2021 Jun 11.

Haematology and Bone Marrow Transplant Unit, IRCSS San Raffaele Scientific Institute, Italy. Electronic address:

Background: Chronic Graft versus Host Disease (GvHD) is a serious complication of allogeneic hematopoietic stem cell transplant that severely impacts quality of life and long-term survival. About 50-to-60 % of patients treated with steroids require a further line of therapy due to lack of sustained response. Ruxolitinib, a JAK1/2 inhibitor, has recently been approved for the treatment of acute GvHD.

Methods: We aimed to retrospectively evaluate ruxolitinib efficacy and safety in a cohort of patients diagnosed with moderate (25 %) or severe (75 %) steroid-refractory or steroid-dependent chronic GvHD. Response evaluation was performed at three and six months.

Results: Thirty-six patients received ruxolitinib after a median of three previous lines (range, r 1-11) for a median of 8.6 months (r 1-51.6). Cutaneous GvHD was the most frequent presentation. We observed an overall response of 59 % (CR 9%, PR 50 %) at three months and 62 % (CR 15 %, PR 46 %) at six months. Two patients had hematologic disease recurrence and were censored at relapse; no other permanent discontinuation due to adverse events were documented. Cutaneous, oral, genital and ocular GvHD significantly improved after treatment. 2-year overall survival and 2-year transplant related mortality were 74 % and 19 % respectively. Ruxolitinib was associated with a significant reduction of steroid dose.

Conclusion: Ruxolitinib was confirmed to be a safe and effective option as salvage treatment also for advanced stages of chronic GvHD. Longer follow up is needed to evaluate durability of response. Prospective analyses on larger cohorts are ongoing.
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http://dx.doi.org/10.1016/j.leukres.2021.106642DOI Listing
June 2021

Posttransplantation Cyclophosphamide- and Sirolimus-Based Graft-Versus-Host-Disease Prophylaxis in Allogeneic Stem Cell Transplant.

Transplant Cell Ther 2021 Jun 1. Epub 2021 Jun 1.

Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising graft-versus-host-disease (GVHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical donors and more recently in matched donor transplants. Herein, we describe our real-life experience on 249 adult patients undergoing allogeneic HSCT, from HLA-matched related (MRD), HLA-matched unrelated (MUD), or mismatched related donors (MMRD). Patients received unmanipulated peripheral blood stem cells (PBSCs), using a GVHD prophylaxis with PTCy and sirolimus. Mycophenolate mofetil was added in MUD or MMRD. In the HLA-matched donor group (MRD, n = 48, MUD, n = 50), the cumulative incidence of grades II-IV and III-IV acute GvHD was 23% and 9% at 100 days, respectively. The cumulative incidence of chronic GvHD was 25% at 2 years, severe only for 5% of the patients. The cumulative incidences of relapse and transplant-related mortality (TRM) were 31% and 9% at 2 years, respectively. The 2-year overall survival (OS) was 72% and progression-free survival (PFS) 60%; the composite endpoint of GvHD/relapse-free survival (GRFS) was 52% at 2 years. In the haploidentical donor group (n = 151), we documented a cumulative incidence of grades II-IV and III-IV acute GVHD of 35% and 20% at 100 days, respectively, and a cumulative incidence of chronic GvHD of 39% at 2 years. We observed severe chronic GVHD in 15% of the patients. The cumulative incidence of relapse and TRM was 32% and 25% at 2 years, respectively. The 2-year OS was 48%, whereas PFS was 43%; GRFS was 28% at 2 years. However, more patients in the haploidentical group presented high/very high disease risk index (DRI) and higher HCT-comorbidity index. In patients classified in the low-intermediate DRI, 2-year GRFS was 53% in MRD, 65% in MUD, and 46% in haploidentical HSCT (P = .33). Sirolimus-PTCy platform deserves further investigation as an alternative to calcineurin-inhibitor-based GVHD prophylaxis for all donor sources. In patients presenting a low-intermediate DRI, this strategy translates in relevant survival independently from the transplant source.
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http://dx.doi.org/10.1016/j.jtct.2021.05.023DOI Listing
June 2021

High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis.

Clin Infect Dis 2021 04;72(8):1350-1357

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Background: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown.

Methods: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ.

Results: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ.

Conclusions: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.
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http://dx.doi.org/10.1093/cid/ciaa222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075034PMC
April 2021

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

Biol Blood Marrow Transplant 2020 06 28;26(6):1179-1188. Epub 2020 Jan 28.

Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy. Electronic address:

Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant 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.
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http://dx.doi.org/10.1016/j.bbmt.2020.01.013DOI Listing
June 2020

Are we underutilizing bone marrow and cord blood? Review of their role and potential in the era of cellular therapies.

F1000Res 2020 17;9. Epub 2020 Jan 17.

Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA, 98109, USA.

Since the first hematopoietic stem cell transplant, over a million transplants have been performed worldwide. In the last decade, the transplant field has witnessed a progressive decline in bone marrow and cord blood utilization and a parallel increase in peripheral blood as a source of stem cells. Herein, we review the use of bone marrow and cord blood in the hematopoietic stem cell transplant setting, and we describe the recent advances made in different medical fields using cells derived from cord blood and bone marrow.
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http://dx.doi.org/10.12688/f1000research.20605.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970216PMC
October 2020

Lung Ultrasound to Evaluate Invasive Fungal Diseases after Allogeneic Hematopoietic Stem Cell Transplantation.

Infect Chemother 2019 Dec;51(4):386-392

Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy.

Invasive fungal diseases (IFDs) are a leading cause of infection-related-mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In this prospective pilot study, we investigated the use of bedside lung ultrasound (US) in IFD management. Ten consecutive hematological patients, who developed pulmonary IFD after HSCT, were included in the study. Standard computed tomography scan and lung US were performed at IFD diagnosis and 10 days after antifungal treatment. The lung US demonstrated a high sensitivity in the detection of lung lesions at IFD diagnosis and in the follow-up examinations. It is of potential clinical relevance for IFD management in hematological patients.
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http://dx.doi.org/10.3947/ic.2019.51.4.386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940370PMC
December 2019

Interleukin-6 as Biomarker for Acute GvHD and Survival After Allogeneic Transplant With Post-transplant Cyclophosphamide.

Front Immunol 2019 1;10:2319. Epub 2019 Oct 1.

Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Although the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has dramatically improved in the past decade, it is still compromised by transplant-related mortality (TRM), mainly caused by Graft-vs. -Host Disease (GvHD). We conducted a prospective observational study to ascertain the potential of serum interleukin-6 (IL6) levels, measured before conditioning and 7 days after allo-HSCT, in predicting acute GvHD, TRM and survival after allo-HSCT with Post-Transplant Cyclophosphamide (PT-Cy) based GvHD prophylaxis. Between April 2014 and June 2017, we collected samples from 166 consecutive allo-HSCT patients. By ROC analysis, we identified a threshold of 2.5 pg/ml for pre-transplant IL6 and 16.5 pg/ml for post-transplant IL6. Both univariate and multivariate analyses confirmed the ability of high baseline IL6 levels to predict worse OS (HR 4.3; < 0.01) and grade II-IV acute GvHD (HR 1.8; = 0.04), and of high post-transplant IL6 to identify patients with worse OS (HR 3.3; < 0.01) and higher risk of grade II-IV (HR 5; < 0.01) and grade III-IV acute GvHD (HR 10.2; < 0.01). In multivariate analysis, both baseline (HR 6.7; < 0.01) and post-transplant high IL6 levels (HR 3.5; = 0.02) predicted higher TRM. IL6 may contribute to the risk stratification of patients at major risk for aGvHD and TRM, potentially providing a window for additional prophylactic or preemptive strategies to improve the quality of life in the early post-transplant phase and the outcome of allo-HSCT.
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http://dx.doi.org/10.3389/fimmu.2019.02319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779849PMC
October 2020