EBMT GvHD Summit 2019 | Prophylaxis of GvHD – EBMT–ELN working group recommendations

Graft-versus-host disease (GvHD), a reaction of donor immune cells against host tissues, is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to significant morbidity and mortality. Currently there is no standard of care in the prevention of GvHD. Avoiding GvHD complications without interfering with the graft vs leukemia effect remains a major challenge.

On Saturday 18 May 2019 at the 1^st European Society for Blood and Marrow Transplantation (EBMT) GvHD Summit, Warsaw, PL, Olaf Penack from Charité, Berlin, DE, gave a presentation about the recommendations of the EBMT– European Leukemia Net (ELN) consensus working group regarding the prophylaxis of GvHD. The recommendations were produced by a task force of 5 experts and build on consensus statements from 20 EBMT and ELN working group members as well as other transplant experts in the field. GvHD Hub steering committee members Mohamed Mohty, Robert Zeiser, Hildegard Greinix, Arnon Nagler and Grezegorz Basak were also part of the working group. The recommendations are based on the current standard of practice throughout European hematological centres, utilizing a Delphi-like approach (>80% approval of a method led to consensus).

Take home messages:

• The recommendations apply to a common allogeneic HSCT population; standard risk malignancy, adult patients, matched related- (mRD) or unrelated donor (mUD), bone marrow or peripheral blood stem cells.
  • They do not apply to pediatric, haploidentical or mismatched unrelated donor transplantation
• Patients undergoing mRD or mUD transplant should receive a calcineurin inhibitor in combination with an antimetabolite
• Calcineurin inhibitors: tacrolimus or cyclosporine A (CsA) can be administered
  • The recommended CsA target concentration in the first few weeks should be 200-300 mcg/l, and 100-200 mcg/l until 3 months after transplant; duration of therapy should be 6 months.
  • The CsA dose should be tapered from 3 months onward unless there are signs of acute or chronic GvHD.
• Antimetabolites: Commonly methotrexate (MTX) is administered
  • Alternatively, the non-myeloablative antimetabolite mycophenolate mofetil (MMF) can be applied in patients who need a rapid engraftment
    • Mycophenolate mofetil should be given for 30 days in mRD transplantation, and 2-3 months in mUD transplantation
    • In case of persistent disease or relapse and no GvHD, MMF may be stopped early
  • For patients receiving matched mUD transplant antithymocyte globulin (ATG) is recommended, which may also be recommended for mRD transplant

Doctor Penack added that CsA and tacrolimus show equivalent prophylactic profiles. However, as tacrolimus is utilized less than CsA by European centres, and as most physicians do not have sufficient experience with tacrolimus, no additional recommendations regarding the use of this drug were included. He then highlighted that in the future GvHD prophylaxis may include using rabbit ATG in patients who receive matched unrelated donor transplant. This may also be recommended for those patients who undergo matched related donor HSCT and have a high risk of developing GvHD.