Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study

Cytomegalovirus (CMV) is the most clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that can further increase CMV infection risk. Prophylaxis with letermovir, an oral antiviral approved to prevent CMV, has been shown to decrease the incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation, but there is a lack of data confirming this benefit in patients with GVHD. In this single-center, retrospective study, we assessed the incidence of clinically significant CMV infection (CS-CMVi) in allo-HCT patients who received letermovir prophylaxis (n = 119) and who developed aGVHD compared to a control group (n = 143) who did not receive letermovir. Among aGVHD patients, letermovir prophylaxis decreased CS-CMVi in patients with aGVHD (HR 0.08 [95% CI 0.03–0.27], p < 0.001), reduced non-relapsed mortality (p = 0.04) and improved overall survival (p = 0.04). This data suggests that letermovir prophylaxis improves outcomes by preventing CS-CMVi in patients with aGVHD.

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Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz454 ◽

2020 ◽

Vol 221 (Supplement_1) ◽

pp. S23-S31 ◽

Cited By ~ 2

Author(s):

Ghady Haidar ◽

Michael Boeckh ◽

Nina Singh

Keyword(s):

T Cell ◽

Hematopoietic Cell Transplantation ◽

Solid Organ Transplantation ◽

Immune Monitoring ◽

Hematopoietic Cell ◽

Preemptive Therapy ◽

Solid Organ ◽

Cell Transplant ◽

Cmv Infection ◽

Hematopoietic Cell Transplant

Abstract This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.

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Relapse Prediction Post Allogeneic Hematopoietic Cell Transplant for Myelodysplastic Syndromes Is Not Improved with Use of the More Stringent Blast Percentage Categories in the Revised International Prognostic Scoring System

Blood ◽

10.1182/blood.v120.21.2011.2011 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2011-2011

Author(s):

Leyla Shune ◽

Zohar Sachs ◽

Todd E. Defor ◽

Michelle Dolan ◽

Daniel J. Weisdorf ◽

...

Keyword(s):

Scoring System ◽

Disease Burden ◽

Residual Disease ◽

Hematopoietic Cell ◽

International Prognostic Scoring System ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Myeloablative Conditioning ◽

Allogeneic Hematopoietic Cell Transplant ◽

Relapse Prediction

Abstract Abstract 2011 Residual disease at the time of allogeneic hematopoietic cell transplant (HCT) has been shown to adversely affect outcomes in patients with acute myelogenous leukemia (AML). Assessment of the impact of MDS disease burden at HCT on post-transplant outcomes is less well defined. While blast percentage is easily quantified on morphology and flow cytometry, the blast percentage captures only a fraction of the true MDS clone. Consequently, improved measures of residual disease in MDS patients are needed to improve post HCT outcome prediction. We hypothesized that a more stringent blast percentage cutoff as well as an assessment of recognizable residual cytogenetic disease burden would better predict outcome post HCT. Disease burden at HCT was characterized as reported in the Revised International Prognostic Scoring System (IPSS-R) (<2%, >2-<5%, 5–10% and >10%) and by assessment of cytogenetic residual disease by calculating the percent of metaphases with ongoing cytogenetic abnormalities immediately prior to transplant (% positive metaphases <25%, 25–50%, and > 50%). Metaphase data was unavailable in n=7. Those patients with normal cytogenetics (n=26) were classified in the <25% category. One hundred consecutive patients with MDS undergoing allogeneic HCT at the University of Minnesota between 1995 –2011 were studied. Their median age was 52 (18–69). At diagnosis, the majority of patients had either refractory cytopenia of multilineage dysplasia (RCMD) (25%) or refractory anemia with excess blasts (RAEB) 1 or 2 (49%) and were INT-1 (37%) or INT-2/High risk (60%). Donor type was related donor (52%), matched unrelated (13%) and umbilical cord blood (35%). Half received myeloablative conditioning and Karnofsky Performance Status (KPS) > 80 in 95%. Results: (Table) Both higher blast percentage at HCT and high percentage of residual cytogenetically positive cells correlated with inferior overall survival as well as more frequent NRM. Relapse incidence was similar in those with blasts up to 10%. Percentage of abnormal metaphases was not predictive of relapse. Conditioning intensity was the only factor that impacted the 2 year relapse rate with decreased relapse seen with myeloablative conditioning. Conclusion: These data suggest that survival and relapse prediction are not improved by using the more stringent IPSS-R blast cutoff of < 2% versus <5% at HCT. Additionally, our data suggest that use of a disease burden measure as represented by % residual positive metaphases at HCT may serve as another predictor of outcome. Survival and NRM were worse with >10% blasts or > 50% residual positive metaphases. These patients require additional therapy or new strategies to improve post HCT outcomes. A refined measure of disease burden at HCT using both blast count and % residual abnormal metaphases may allow for more comprehensive prediction of post HCT outcomes in MDS. Disclosures: No relevant conflicts of interest to declare.

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Risk of Clinically Significant Graft-Versus-Host Disease (CSGVHD) in Children Receiving Allogeneic Hematopoietic Cell Transplant (HCT) for Non-Malignant Disorders in Florida (2010-2019)

Transplantation and Cellular Therapy ◽

10.1016/s2666-6367(21)00368-7 ◽

2021 ◽

Vol 27 (3) ◽

pp. S289

Author(s):

Mustafa Hanif ◽

Paul Castillo ◽

Mansi Dalal ◽

Edward Ziga ◽

Michael Joyce ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Host Disease ◽

Graft Versus Host ◽

Allogeneic Hematopoietic Cell Transplant ◽

Clinically Significant

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Cytomegalovirus (CMV) Cell-Mediated Immunity and CMV Infection After Allogeneic Hematopoietic Cell Transplantation: The REACT Study

Clinical Infectious Diseases ◽

10.1093/cid/ciz1210 ◽

2020 ◽

Author(s):

Roy F Chemaly ◽

Lynn El Haddad ◽

Drew J Winston ◽

Scott D Rowley ◽

Kathleen M Mulane ◽

...

Keyword(s):

At Risk ◽

Hematopoietic Cell Transplantation ◽

Multivariable Analysis ◽

Hematopoietic Cell ◽

Cell Mediated Immunity ◽

Cell Transplant ◽

Cmv Infection ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant ◽

Patients At Risk

Abstract Background Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). Methods The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. Results CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (P < .0001). Patients with CS-CMVi had higher all-cause mortality (P = .007), especially those with low CMV-CMI (P = .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. Conclusions Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.

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