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Clinical case of the month - Stem Cell Transplantation during COVID 19 pandemic

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May 2020 Clinical Case of the Month

Title: Stem Cell Transplantation during COVID 19 pandemic
Submitted by: Syed Ali Abutalib and Nicolaus Kröger
Physicians expert perspective: Alessandro Rambaldi

In a time of COVID-19 pandemic a 34-year-old asymptomatic female patient with acute myeloid leukemia (AML) presents for scheduled visit to sign consents for allogeneic transplant. She has unfavorable risk group AML (monosomal karyotype) but with successful induction and one cycle of consolidation chemotherapy she remains in first complete remission (CR1). Fortunately, she has a 10/10 HLA matched unrelated donor available and ready. Both, the donor and recipient are ABO and CMV matched. In the admitting hospital there are currently 10 (ten) COVID-19 patients in a dedicated COVID-19 unit and 3 (three) are on mechanical ventilation in intensive care unit (ICU). In the transplant unit, no patient has COVID-19. The ICU has total of 20 (twenty) fully equipped beds and the transplant unit has 12 (twelve) HEPA (high-efficiency particulate air) filtered beds.

Which of the following options is less in line with the recent EBMT recommendation about haematopoietic stem cell transplantation during COVID-19 pandemic?

  1. Proceed with conditioning regimen and allogeneic haematopoietic stem cell transplantation without further delay given patient is extremely high-risk for relapse
  2. Cryopreserve unrelated haematopoietic stem cell product before starting conditioning regimen
  3. Screen patients for SARS-CoV-2 prior to hospital admission and if positive then delay the transplant
  4. Continue with consolidation therapy for total of 4 cycles +/- maintenance therapy and reserve allogeneic transplant for early relapse
  5. Screen patient with chest imaging for subclinical abnormal radiologic findings if SARS-CoV-2 test is positive
  6. If a decision is made to start conditioning regimen then it is best to avoid marrow graft at this time

Expert Perspective by Professor Alessandro Rambaldi

Acute leukemia patients are particularly at risk of developing serious respiratory adverse events related to COVID-19 [1]. At the same time, any inappropriate delay of a life-saving treatment such as allogeneic transplantation may be detrimental for their survival.

This clinical case describes a typical scenario of clinical decision making in the COVID-19 pandemic era. We are discussing here a young patient affected by acute myeloid leukemia (AML) with an unfavorable cytogenetic (monosomal karyotype), in first complete remission (CR1) after induction therapy and one consolidation cycle. According to the ELN risk classification and EBMT guidelines, there is a clear indication to proceed to allogeneic haematopoietic stem cell transplantation, since delaying treatment poses the patient at very-high-risk of relapse.

During this COVID-19 pandemic era, any patient for whom an allogeneic transplant is planned should be tested with nasopharyngeal swab for SARS-CoV-2 infection especially prior to hospital admission.  If the swab result is positive, then the transplant should be deferred. Asymptomatic COVID-19 patient should be monitored for respiratory symptoms, clinically and by a CT scan to detect the presence of a subclinical interstitial pneumonia. A mildly symptomatic COVID-19 patient should be quarantined and followed up until resolution of symptoms. For asymptomatic patients a new swab should be repeated after 14 to 21 days. Conditioning regimen may reasonably be re-planned after at least 2 negative PCR swabs (taken at least 24 hours apart) and without any abnormality on chest imaging.

If the result for SARS-CoV-2 infection proves negative, the transplant procedure should be pursued as planned but the following concerns about the safety of hematopoietic stem cell donation should be kept in mind.

  1. Donors may become suddenly unavailable to donate due to infection with COVID-19 or due to logistical reasons at the harvest centers. For these reasons the EBMT guidelines recommend collecting, freeze and made available the stem cell harvest before the conditioning regimen is initiated.
  2. Mobilized peripheral blood stem cells should be preferentially used since a bone marrow harvest is logistically more complicated and requires anesthesiologist assistance, which can be difficult to guarantee in an emergency situation.
  3. It is important, now more than ever, that hematopoietic stem cell transplantations should be performed only in well-equipped hospitals. A clear separation between patients with and without COVID-19 (possibly with dedicated health staff) is mandatory, as well as the availability of sufficient intensive care unit beds and ventilators.  During the COVID-19 pandemic crisis, many excellent transplant programs have been challenged because the intensive care units were overwhelmed by COVID-19 patients. For this reason, the effective availability of ICU spaces must be guaranteed. Otherwise the transplant procedure should be moved to another center.

In conclusion, we would test the patient for SARS-CoV-2 infection and if negative we would proceed with allogeneic haematopoietic stem cell transplant without any further delay.

Correct Answer – D is incorrect option

References

  1. Liang, The Lancet Oncology, 2020
  2. Coronavirus disease COVID-19: EBMT recommendations update April 21,2020
  3. Ljungman P, et al, BMT 2020, in press

Contacts

Syed Ali Abutalib, MD
Associate Director, Hematology and Cellular Therapy Program
Director, Clinical Apheresis Program
Cancer Treatment Centers of America, Zion, Illinois
Associate Professor, Rosalind Franklin University of Medicine and Science
Email: abutalib110@gmail.com

Nicolaus Kröger, MD
Professor and Medical Director of the Department of Stem Cell
Transplantation at the University Hospital Hamburg-Eppendorf, Germany
University Hospital Hamburg, Hamburg, Germany

Correspondence: Nicolaus Kröger, MD
Email: nkroeger@uke.uni-hamburg.de

Expert Perspective

Alessandro Rambaldi, MD
Professor of Hematology - University of Milan
Head, Hematology and Bone Marrow Transplant Unit, 1 - 24127 Bergamo/Italy
arambaldi@asst-pg23.it
alessandro.rambaldi@unimi.it

Future Clinical Case of the Month

If you have a suggestion for future clinical case to feature, please contact Nicolaus Kröger.