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CME / ABIM MOC / CE

Do COVID-19 Outcomes Differ for Stem Cell Transplant Patients?

  • Authors: MDEdge News Author: Sharon Worcester; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 5/7/2021
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 5/7/2022
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Target Audience and Goal Statement

This activity is intended for hematologists/oncologists, nurses, infectious disease clinicians, pharmacists and other members of the healthcare team caring for hematopoietic stem-cell transplantation (HSCT) recipients with or at risk for COVID-19.

The goal of this activity is to describe the characteristics and outcomes of HSCT recipients after developing COVID-19, according to an analysis of new data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Upon completion of this activity, participants will:

  • Describe the characteristics and outcomes of HSCT recipients after developing COVID-19, according to an analysis of new CIBMTR data
  • Identify clinical implications of the characteristics and outcomes of HSCT recipients after developing COVID-19, according to an analysis of new CIBMTR data
  • Outline implications for the healthcare team


Disclosures

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Medscape, LLC, encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.


MDEdge News Author

  • Sharon Worcester

    Disclosures

    Disclosure: Sharon Worcester has disclosed no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Editor/Nurse Planner

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

CME Reviewer

  • Esther Nyarko, PharmD

    Associate Director, Accreditation and Compliance
    Medscape, LLC

    Disclosures

    Disclosure: Esther Nyarko, PharmD, has disclosed no relevant financial relationships.

Medscape, LLC staff have disclosed that they have no relevant financial relationships.


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CME / ABIM MOC / CE

Do COVID-19 Outcomes Differ for Stem Cell Transplant Patients?

Authors: MDEdge News Author: Sharon Worcester; CME Author: Laurie Barclay, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CME / ABIM MOC / CE Released: 5/7/2021

Valid for credit through: 5/7/2022

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Note: The information on the coronavirus outbreak is continually evolving. The content within this activity serves as a historical reference to the information that was available at the time of this publication. We continue to add to the collection of activities on this subject as new information becomes available. It is the policy of Medscape Education to avoid the mention of brand names or specific manufacturers in accredited educational activities. However, manufacturer names related to COVID-19 vaccines may be provided in this activity to promote clarity. The use of manufacturer names should not be viewed as an endorsement by Medscape of any specific product or manufacturer.

Clinical Context

Patients with cancer have at least twice the risk for COVID-19--associated intensive care unit admission, invasive ventilation, and death compared with the general population. Hematopoietic stem cell transplant (HSCT) recipients may be especially vulnerable because of nascent immune systems or treatment-related organ toxicities.

Study Synopsis and Perspective

Among individuals who have received an HSCT, often used in the treatment of blood cancers, rates of survival are poor for those who develop COVID-19.

The probability of survival 30 days after being diagnosed with COVID-19 is only 68% for persons who have received an allogeneic HSCT and 67% for autologous HSCT recipients, according to new data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

These findings underscore the need for "stringent surveillance and aggressive treatment measures" in this population, say authors Akshay Sharma, MBBS, of St Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues.

The findings were published in the March issue of The Lancet Haematology.[1]

The study is "of importance for physicians caring for HSCT recipients worldwide," commented Mathieu Leclerc and Sébastien Maury, Hôpitaux universitaires Henri-Mondor, Créteil, France, in an accompanying editorial.[2]

Study Details

For their study, Sharma and colleagues analyzed outcomes for all HSCT recipients who developed COVID-19 and whose cases were reported to the CIBMTR. Of 318 such patients, 184 had undergone allogeneic HSCT, and 134 had undergone autologous HSCT.

Overall, about half of these patients (49%) had mild COVID-19.

Severe COVID-19 that required mechanical ventilation developed in 15% and 13% of the allogeneic and autologous HSCT recipients, respectively.

About one-fifth of patients died: 22% and 19% of allogeneic and autologous HSCT recipients, respectively.

Factors associated with greater mortality risk included age of ≥ 50 years (HR = 2.53 [95% CI: 1.16, 5.52]; male sex (HR = 3.53 [95% CI: 1.44, 8.67]); and development of COVID-19 within 12 months of undergoing HSCT (HR = 2.67 [95% CI: 1.33, 5.36]).

Among autologous HSCT recipients, lymphoma was associated with higher mortality risk in comparison with a plasma cell disorder or myeloma (HR = 2.41 [95% CI: 1.08, 5.38]), the authors noted.

"Two important messages can be drawn from the results reported by Sharma and colleagues," Leclerc and Maury wrote in their editorial. "The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns."

The second relates to the risk factors for death among HSCT recipients who develop COVID-19. In addition to previously known risk factors, such as age and sex, the investigators identified transplant-specific factors potentially associated with prognosis: namely, the nearly 3-fold increase in death among allogeneic HSCT recipients who develop COVID-19 within 12 months of transplant, they explained.

Still, the findings are limited by a substantial amount of missing data, short follow-up, and the possibility of selection bias, they noted.

"Further large and well-designed studies with longer follow-up are needed to confirm and refine the results," the editorialists wrote.

"[A] better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step towards improvement of the remarkably poor prognosis observed in this setting," they added.

The study was funded by the American Society of Hematology; the Leukemia and Lymphoma Society; the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; the Health Resources and Services Administration; and the Office of Naval Research. Sharma receives support for the conduct of industry-sponsored trials from CRISPR Therapeutics AG; Novartis Pharmaceuticals Corporation; and Vertex Pharmaceuticals, Inc. and consulting fees from Spotlight Therapeutics. Leclerc and Maury have disclosed no relevant financial relationships.

Study Highlights

  • On March 27, 2020, CIBMTR implemented a special form to capture COVID-19--related data.
  • This analysis included all patients regardless of age, diagnosis, donor type, graft source, or conditioning regimens (n = 318), with data cutoff of August 12, 2020.
  • Overall survival 30 days after COVID-19 diagnosis, calculated using Kaplan-Meier estimator, was the main outcome.
  • Cox proportional hazard models allowed assessment of factors associated with mortality after COVID-19 diagnosis.
  • Median time from HSCT to COVID-19 diagnosis was 17 (interquartile range [IQR], 8-46) months for allogeneic HSCT recipients and 23 (IQR, 8-51) months for autologous HSCT recipients.
  • Median follow-up of survivors was 21 (IQR, 8-41) days for allogeneic HSCT recipients and 25 (IQR, 12-35) days for autologous HSCT recipients.
  • Within 6 months of COVID-19 diagnosis, 34 (18%) of 184 allogeneic HSCT recipients were receiving immunosuppression.
  • Disease severity was mild in 155 (49%) of 318 patients.
  • Severe disease requiring mechanical ventilation occurred in 45 (14%) of 318 patients (15% of 184 allogeneic HSCT recipients and 13% of autologous HSCT recipients).
  • Overall survival at 30 days after COVID-19 diagnosis was 68% (95% CI: 58, 77) for allogeneic HSCT recipients and 67% (95% CI: 55, 78) for autologous HSCT recipients.
  • Factors associated with higher mortality risk among allogeneic HSCT recipients were age ≥ 50 years (HR ratio = 2.53 [95% CI: 1.16, 5.52]; P = .02); male sex (HR = 3.53 [95% CI: 1.44, 8.67]; P = .006), and COVID-19 occurring within 12 months of transplantation (HR = 2.67 [95% CI: 1.33, 5.36]; P = .005).
  • In autologous HSCT recipients, a disease indication of lymphoma vs plasma cell disorder or myeloma was associated with higher mortality risk (HR = 2.41 [95% CI: 1.08, 5.38]; P = .033).
  • Immunosuppression within 6 months of developing COVID-19 was not associated with survival in this study.
  • The investigators concluded that recipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival.
  • The findings highlight the need for stringent surveillance and aggressive treatment measures in HSCT recipients who develop COVID-19.
  • Patients with cancer, especially hematological cancers, have a high risk of developing severe disease and death from COVID-19.
  • After HSCT, patients might be at additional risk for severe COVID-19 from GvHD prophylaxis or treatment and transplantation-related morbidities.
  • Estimated 30-day overall survival after COVID-19 diagnosis was similar to that in Italian and North American cohorts.
  • This study did not support the hypothesis that immunosuppression might reduce lung inflammation intensity and hence mortality in HSCT recipients developing COVID-19, as immunosuppression within 6 months of developing COVID-19 was not associated with survival.
  • Most studies identified cancer survivors aged > 60 years to be at highest risk for mortality or adverse outcomes after COVID-19, but the age cutoff for HSCT recipients in this study was slightly lower (age > 50 years).
  • This may reflect HSCT recipients’ additional toxicity burden and possibly higher frailty and comorbidity burden, although the HSCT-comorbidity index at the time of HSCT, which was used as a surrogate for preexisting comorbid conditions, was not associated with survival in this analysis.
  • Study limitations include inability to determine efficacy of drugs or treatments or account for various comorbidities; observational design; modest sample size; and possible selection bias.
  • As more data become available, future directions should include evaluation of treatment effects on outcome, associated coinfections, and better identification of risk factors for mortality in HSCT recipients with COVID-19.
  • An accompanying editorial calls for additional large, well-designed studies with longer follow-up to confirm and refine the results.
  • Clarifying the distinctive features of COVID-19 in HSCT recipients is crucial to improve the dismal prognosis seen in this setting.

Clinical Implications

  • Recipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival.
  • The findings highlight the need for stringent surveillance and aggressive treatment in HSCT recipients who develop COVID-19.
  • Implications for the Healthcare Team: Patients with cancer, especially hematological cancers, have a high risk of developing severe disease and death from COVID-19; after HSCT, patients might be at additional risk for severe COVID-19 from GvHD prophylaxis or treatment and transplantation-related morbidities. Care for these patients should be coordinated accordingly to improve patient outcomes.
 

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