Summary of four EBMT recent studies published in peer-reviewed journalsEBMT−NIH−CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Helene M. Schoemans, et al. Bone Marrow Transplant 2018 [Epub ahead of print 5 June]
Several international recommendations address the assessment of acute and chronic graft-versus-host disease (GvHD). However, in clinical practice, application of such recommendations differs widely among HCT clinicians. Even among very experienced allogeneic HCT centers and GvHD professionals, studies have shown a lack of adherence to recommendations and inconsistencies in acute and chronic GvHD evaluation. Such inaccuracies are likely to be even more prominent among less experienced centers. In addition to clinical practice, the adherence to a common set of GvHD criteria is vitally important to improve the quality of data, to compare results of retrospective and prospective studies, and to make therapeutic recommendations based on quality evidence. In this manuscript, a group of GvHD experts from the EBMT, NIH, and CIBMTR have joined forces to: (1) review the existing guidelines for both acute and chronic GvHD and recommend those best supported by clinical evidence; (2) address confusions that arise in real-life scenarios encountered in clinical practice; and (3) develop consensus definitions for key terms frequently used in the evaluation and monitoring of GvHD. This task force panel provides a historical perspective on the currently available guidelines and advocates the use of the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria for acute GvHD and the NIH 2014 criteria for chronic GvHD as the most comprehensive and detailed criteria currently available. In addition, this position statement offers practical guidance for the implementation of these recommendations in clinical practice and provides a set of consensus definitions for a lexicon of commonly used GvHD terms and concepts in order to facilitate future clinical and translational research in this field. To assist the dissemination of these recommendations, a web-application based on this position statement is available (https://www.uzleuven.be/egvhd).
The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation. Stefan O. Ciurea, et al. Bone Marrow Transplant 2018;53:521-534.
Donor-specific anti-HLA antibodies (DSA) are increasingly recognized as a barrier to the success of allogeneic HCT in the setting of HLA disparities. Beyond cord-blood and mismatched unrelated donor transplantation, DSA are becoming a more prevalent issue with the marked increase in the use of haploidentical HCT, which with the higher degree of HLA-mismatch and likelihood of alloimmunization of multiparous women against offspring’s HLA antigens is making the need to address DSA a top priority. In this context, the EBMT has produced this timely manuscript summarizing the evidence available on the role of DSA in the development of graft failure after haploidentical HCT and providing consensus recommendations on testing, monitoring and treatment of DSA in haploidentical HCT candidates. The study revises patients’ risk to develop DSA, describes the tools available to identify anti-HLA antibodies, their mechanism of action and functionality, as well as the cut-off levels which may associate with a more detrimental effect on engraftment. The manuscript gives recommendations on management, including DSA testing as part of donor selection prior to transplantation, and in the absence of an alternative suitable donor, provides a number of options for antibody neutralization and removal, inhibition of antibody production, blockage of complement cascade, as well as for monitoring of DSA levels after treatment and haploidentical HCT.
Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? Tara M. Robinson, et al. Blood Advances 2018;2(11):1180-1186.
This joint study by the EBMT Acute Leukemia Working Party and the CIBMTR aims to ascertain whether the use of posttransplantation cyclophosphamide (PTCy) abrogates the detrimental effect of HLA mismatch in haploidentical HCT compared to matched-siblings, and whether the age of the haploidentical donor (sibling versus offspring) may impact transplant outcomes more than histocompatibility. The study includes 218 haploidentical sibling donor HCT for patients aged 18 to 54 years and 218 haploidentical offspring donor HCT for patients aged 55 to 76 years. Transplant outcomes were compared separately for the two patient age groups to a total of 1707 HLA-identical sibling donor HCT. In younger patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant. In older patients aged 55 to 76 years, despite lower chronic GVHD, graft failure, nonrelapse mortality, and overall mortality were higher after transplant from offspring compared with an HLA-matched sibling. Despite the limitations of the retrospective analysis, primarily driven by the differences in transplant platforms (GvHD prophylaxis and graft type), these data suggest that PTCy eliminates the detrimental impact of HLA mismatching for younger adults with acute leukemia transplants when the haploidentical donor is a sibling, but for older patients for whom the haploidentical donor is an offspring, transplantation from an HLA-matched sibling offers better outcomes and survival. These findings become increasingly more relevant as reduced-intensity conditioning regimens have enabled the transplantation of older patients, most of whom have offspring, for whom donor selection often involves choosing between an HLA-matched or -haploidentical sibling of similar age, or an offspring, typically 2 to 3 decades younger than the patient. The results may differ if the transplant platforms were similar. Clinical trials to explore whether PTCy can further improve the outcomes of matched-sibling HCT from the current standards are warranted.
Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation. Christoph Schmid, et al. Haematologica 2018;103(2):237-245.
This manuscript by the EBMT chronic malignancies working party reports on the outcomes and treatment strategies of a large series of 698 patients with myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML) who relapsed after allogeneic HCT, for whom there is no current standard of therapy. The median overall survival from relapse for the group was 4.7 months and the 2-year survival rate was 17.7%. Factors with a negative impact on survival included a shorter remission after transplantation, advanced disease, older age, unrelated donor and acute graft-versus-host disease before relapse. At 6 months from relapse, the majority of patients had received palliative chemotherapy or best supportive care without any additional cellular treatment (375; 54%), 213 (30%) had received donor lymphocyte infusions, and 110 (18%) had received a second allogeneic HCT. Of the 375 patients who did not receive any additional cellular therapy, 109 (29%) were alive at 6 months after relapse. These cases achieved a median overall survival from this landmark of 9 months and a 2-year survival rate of 30%. Recipients of DLI achieved a median survival from first infusion of 6 months with a 2-year survival rate of 28%. Longer remission after first transplantation and younger age predicted better outcome. Among recipients of a second allogeneic HCT, the median survival from second HCT was 4.2 months and their 2-year survival rate was 17.0%. Longer remission after first transplantation, complete remission at second transplant, no prior chronic graft-versus-host disease and change to a new donor predicted better outcome. Despite the intrinsic limitations of the retrospective design and the imbalanced characteristics of the groups, this study identifies patients benefiting from donor lymphocyte infusion and second transplantation and may serve as a baseline for prospective trials that may incorporate promising drugs such as hypomethylating agents, checkpoint inhibitors, histone deacetylase inhibitors or drugs targeting particular molecular aberrations.
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