publication date: Mar. 27, 2020

Trials & Tribulations

Against all odds

Unrelated stem cell transplants in coronavirus times

Steven Devine

By Steven Devine

Chief Medical Officer, National Marrow Donor Program

 

Alexander Schmidt

Alexander Schmidt

Global Chief Medical Officer, DKMS

 

This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.

The COVID-19 crisis has consequences not only for those who have become infected and the doctors and nurses who care for them. The care of other patients is also threatened by the increasing stress that national health systems and societies as a whole are under.

Also, cancer has no borders, and patients in need continue to need our help. Against all odds, we care for unrelated stem cell transplants in these difficult times. As chief medical officers of the National Marrow Donor Program (NMDP) and German-based DKMS, the two world’s largest volunteer bone marrow and blood stem cell donor organizations, for us safeguarding our donors is always our highest priority.

Currently, more than 37 million donors are registered worldwide. In 2019 alone we have been working closely together to get 1,734 international DKMS donated stem cells for patients to the United States.

In times of COVID-19, several organizations have worked collaboratively to develop enhanced guidelines for the assessment of volunteer unrelated blood/bone marrow donors during the COVID-19 crisis to limit the risk both of viral transmission and any additional adverse events to the donors.

A question was raised in a recent issue of The Cancer Letter that perhaps a haploidentical related donor might be preferred, given all the uncertainties imposed by the current COVID-19 crisis (The Cancer Letter, March 13).

Yet, unrelated donor BMT remains the most widely used platform of allogeneic transplantation, with the largest body of evidence and the longest clinical follow-up.1 Many retrospective observational studies have been published suggesting overall survival and other important clinical outcomes may be equivalent comparing matched unrelated donor to haploidentical donor transplantation.

These studies are important but are confounded and typically underpowered to detect clinically relevant differences.2 The largest analysis performed to date concluded that absent a matched related donor, a matched unrelated donor remains the next best option for most patients.3

Today, general consensus is that if a well matched volunteer donor can be identified and made available in a reasonable time frame, that donor is preferred  to a haploidentical related donor.

Since donor and patient should match their human leukocyte antigens (HLA) as closely as possible and the HLA system is extremely diverse, a large number of potential stem cell donors is needed.

Ultimately, decisions about the optimal donor are best made by the treatment teams at the transplant centers. Our goal is to help procure unrelated donor blood or bone marrow if that is the best choice for their patients.

We acknowledge the tremendous sacrifices our donors make when they consent to donate bone marrow or blood stem cells in an effort to save a patient’s life. During the COVID-19 crisis, efforts to mitigate the spread of SARS-CoV-2 have imposed substantial travel restrictions that the NMDP, DKMS and other registries have worked diligently to overcome.

Just over a week ago, the NMDP Patient Advocacy group worked tirelessly with US legislators and ultimately received a blanket travel ban waiver, almost certainly the only of its kind in the country, signed by the Director of the Centers for Disease Control and Prevention.

This ensures that European couriers can transport products into the US despite the travel ban. The waiver ban has been distributed to European embassies and US ports of entry, allowing non-US citizens to enter the US with donor products despite the travel ban.

In this chaotic situation, it is perfectly normal for transplant physicians and coordinators to wonder whether the stem cell product of an unrelated donor from another continent should really be the preferred therapy option for their patient.

Although there are concerns regarding donor availability during the COVID-19 pandemic: DKMS, thanks to the NMDP blanket travel ban waiver, signed by the director of the CDC, has transported 40 stem cell products from European DKMS donors successfully to the United States last week alone.

Each requested product could be delivered properly.

We know that further challenges are very likely to await in the coming weeks and months. It is reasonable to assume that passenger air traffic will be further reduced or stopped altogether. Preparations for this scenario are in full swing.

Together with highly dedicated airlines and courier companies, successful tests have already been conducted to transport the stem cell products in the cockpits of cargo planes without a dedicated courier. This process could perhaps become the new standard for the further course of the crisis.

In order to further ensure patient safety, most international registries are now strongly recommending that unrelated donor products be collected prior to initiation of patient conditioning. This will guarantee the donor graft is available on the intended day of transplantation.

In fact, the NMDP has just made cryopreservation prior to conditioning a requirement, and others may follow suit.

Collectively, the volunteer unrelated donor community, together with the transplant centers, is working collaboratively day and night to continue uninterrupted our commitment to connect these remarkable donors with their patients.

We are still receiving many requests for unrelated donor products, as transplant centers continue to believe this is in the best interests of their patients.   


References:

  1. Fleischhauer K. Selection of matched unrelated donors moving forward: from HLA allele counting to functional matching. Hematology Am Soc Hematol Educ Program. 2019 Dec 6;2019(1):532-538

  2. Shaw BE. Related haploidentical donors are a better choice than matched unrelated donors: Counterpoint. Blood Adv. 2017 Feb 14;1(6):401-406.

  3. Shouval R, Fein JA, Labopin M, Kröger N, Duarte RF, Bader P, Chabannon C, Kuball J, Basak GW, Dufour C, Galimard JE, Polge E, Lankester A, Montoto S, Snowden JA, Styczynski J, Yakoub-Agha I, Mohty M, Nagler A. Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis Lancet Haematol. 2019 Nov;6(11):e573-e584. doi: 10.1016/S2352-3026(19)30158-9.

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