EBMT NEWSLETTER | November 2017 | Volume 59 - Issue 5

Important dates

Summary of four EBMT recent studies published in peer-reviewed journals

High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A retrospective study by the European Society for Bloodand Marrow Transplantation (EBMT)-Lymphoma Working Party.
Akhtar S, Montoto S, Boumendil A, Finel H, Masszi T, Jindra P, Nemet D, Fuhrmann S, Beguin Y, Castagna L, Ferrara F, Capria S, Malladi R, Moraleda JM, Bloor A, Ghesquières H, Meissner J, Sureda A, Dreger P.
Am J Hematol. 2017 Oct 3. doi: 10.1002/ajh.24927. [Epub ahead of print]
PMID: 28971503

This retrospective study by the Lymphoma WP is the first one to address the role of autologous HCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a subtype for which data and transplant recommendations and are not so well established as for relapsed/refractory classical HL. Cases transformed to diffuse large B cell lymphoma were excluded. A total of 60 adult recipients of a first autologous HCT for NLPHL were included. Prior to HCT, cases had a median of 21 months from diagnosis (IQR 13-58) and 2 lines of therapy (1-5), including rituximab in 63%. All patients had chemosensitive disease to salvage therapy, having achieved CR in 62% and PR in 38% of cases at HCT. Seventy-two percent of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year PFS and OS were 66% and 87%, respectively. The only pre-HCT factor which showed a statistical association with HCT outcomes was being in CR (vs PR) at the time of HCT, which increased OS (p=0.049). This study shows that autologous HCT provides excellent disease control and long-term PFS and PS in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy.

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review From the Late Effects and Quality of Life Working Committee of the CIBMTR and Complications and Quality of Life Working Party of the EBMT.
Kelly DL, Buchbinder D, Duarte RF, Auletta JJ, Bhatt N, Byrne M, Gabriel M, Mahindra A, Norkin M, Schoemans H, Shah AJ, Ahmed I, Atsuta Y, Basak GW, Beattie S, Bhella S, Bredeson C, Bunin N, Dalal J, Daly A, Gajewski J, Gale RP, Galvin J, Hamadani M, Hayashi RJ, Adekola K, Law J, Lee CJ, Liesveld J, Malone AK, Nagler A, Naik S, Nishihori T, Parsons SK, Scherwath A, Schofield HL, Soiffer R, Szer J, Twist I, Warwick A, Wirk BM, Yi J, Battiwalla M, Flowers ME, Savani B, Shaw BE.
Biol Blood Marrow Transplant. 2017 Sep 19. pii: S1083-8791(17)30698-5. doi: 10.1016/j.bbmt.2017.09.004. [Epub ahead of print] Review.
PMID: 28939455

The EBMT Transplant Complications WP and the CIBMTR Late Effects and Quality of Life WC have undertaken a state-of-the-science review of neurocognitive dysfunction and its impact on survivorship and quality of life following HCT. Despite the increasing awareness of the importance of this problem in cancer patients and HCT survivors, there are important gaps including an operational definition, the evaluation of risk factors, the broad assessment of this complication in HCT recipients and the potential interventions to prevent and treat this complication.  The main aim of this review manuscript is to help clinicians understand the scope of this problem, highlight its impact on HCT survivors’ well-being, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. The authors define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions both for preventing and treating HCT recipients with this condition. In addition, they highlight the need for well-designed studies to develop and test interventions in this area.

Haploidentical hematopoietic cell transplantation for adult acute myeloid leukemia: A position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
Lee CJ, Savani BN, Mohty M, Labopin M, Ruggeri A, Schmid C, Baron F, Esteve J, Gorin NC, Giebel S, Ciceri F, Nagler A.
Haematologica. 2017 Sep 7. pii: haematol.2017.176107. doi: 10.3324/haematol.2017.176107. [Epub ahead of print]
PMID: 28883081

As we know from the EBMT activity survey reports, the use of haploidentical transplantation among EBMT centres has increased dramatically in the past decade (by 250% since 2010). Although initial reports of haploidentical transplantation in this period seemed to favour its use in some lymphoid malignancy indications, acute myeloid leukaemia remains the main indication for allogeneic HCT, and has also shown a marked increase in haploidentical activity. Thus, the Acute Leukemia WP has carried out this position statement on the use of haploidentical transplantation in patients with acute myeloid leukemia. The manuscript reviews the technical advances from the early experiences in haploidentical transplantation from the University of Perugia in the early nineties to the current use of post-transplant chyclophosphamide as a pivotal point in the field, from the experiences from Johns Hopkins and Beijing University. Also, the authors review the efficacy of haploidentical hematopoietic cell transplantation for acute myeloid leukemia from available studies, including preliminary comparative studies with other donor types and cell sources, and bringing attention to remaining unanswered questions and directions for future research. The manuscript concludes that haploidentical donor transplantation is a valid option for patients with AML lacking a matched sibling or unrelated donor, and that in certain clinical situations, especially in the case of a need for an urgent transplant procedure, a readily available haploidentical donor may be considered over initiating an unrelated donor search. However, it also summarises that the current evidence for the superiority of haploidentical versus other alternative donors, and of one haploidentical HCT platform over another, are insufficient. Economic factors, together with individual center experience, may be decisive.

Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation: a retrospective analysis of the EBMT chronic malignancies working party.
Scheid C, de Wreede L, van Biezen A, Koenecke C, Göhring G, Volin L, Maertens J, Finke J, Passweg J, Beelen D, Cornelissen JJ, Itälä-Remes M, Chevallier P, Russell N, Petersen E, Milpied N, Richard Espiga C, Peniket A, Sierra J, Mufti G, Crawley C, Veelken JH, Ljungman P, Cahn JY, Alessandrino EP, de Witte T, Robin M, Kröger N.
Bone Marrow Transplant. 2017 Sep 11. doi: 10.1038/bmt.2017.171. [Epub ahead of print]
PMID: 28892084
The Chronic Malignancies WP has undertaken this retrospective analysis to validate the use of the International Prognostic Scoring System (IPSS-R) to predict the prognosis of patients with MDS at the time of allogeneic HCT. A total of 579 patients had sufficient information available to calculate IPSS-R at transplant, and showed that IPSS-R score pretransplant strongly associates with key outcomes such as relapse-free survival (RFS) and overall survival (OS). Median RFS showed significant differences according to IPSS-R (very low: 23.6 months, low: 24.8 months, intermediate 10.6 months, high 7.9 months, very high 5.5 months; P<0.001). Multivariate risk factors for RFS were IPSS-R, reduced intensity conditioning, graft source and prior treatment. Median OS was also significantly different according to IPSS-R (very low: 23.6 months, low: 55.0 months, intermediate: 19.7 months, high: 13.5 months, very high: 7.8 months; P<0.001). Multivariate risk factors for OS were IPSS-R, graft source, age and prior treatment. In summary, the study shows that IPSS-R score at transplant includes many of disease- and therapy-related factors in one score and may help to identify patients with a favorable transplant outcome and those needing additional pre- or post-transplant interventions to improve prognosis.


The survey on cellular and tissue-engineered therapies in Europe and neighboring Eurasian countries in 2014 and 2015.
Ireland H, Gay MHP, Baldomero H, De Angelis B, Baharvand H, Lowdell MW, Passweg J, Martin I; International Society for Cellular Therapy (ISCT); Tissue Engineering and Regenerative Medicine International Society—Europe (TERMIS-EU); International Cartilage Repair Society(ICRS); International Federation for Adipose Therapeutics (IFAT); European Group for Bloodand Marrow Transplantation.
Cytotherapy. 2017 Oct 4. pii: S1465-3249(17)30668-0. doi: 10.1016/j.jcyt.2017.08.009. [Epub ahead of print]
PMID: 28988692

Relatively favourable outcome after allogeneic stem cell transplantation for BCR-ABL1-positive AML: A survey from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
Lazarevic VL, Labopin M, Wu D, Yakoub-Agha I, Huynh A, Ljungman P, Schaap N, Cornelissen JJ, Maillard N, Pioltelli P, Gedde-Dahl T, Lenhoff S, Houhou M, Esteve J, Mohty M, Nagler A.
Am J Hematol. 2017 Oct 3. doi: 10.1002/ajh.24928. [Epub ahead of print]
PMID: 28971504

Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukemia: a report from Eurocord and the ALWP of the EBMT.
Baron F, Ruggeri A, Beohou E, Labopin M, Mohty M, Sanz J, Vigouroux S, Furst S, Bosi A, Chevallier P, Cornelissen JJ, Michallet M, Sierra J, Karakasis D, Savani BN, Gluckman E, Nagler A.
J Intern Med. 2017 Oct 4. doi: 10.1111/joim.12696. [Epub ahead of print]
PMID: 28977716

Mixed phenotype acute leukemia: Outcomes with allogeneic stem cell transplantation, a retrospective study from the Acute Leukemia Working Party of the EBMT.
Munker R, Labopin M, Esteve J, Schmid C, Mohty M, Nagler A.
Haematologica. 2017 Sep 29. pii: haematol.2017.174441. doi: 10.3324/haematol.2017.174441. [Epub ahead of print]
PMID: 28971902

Unrelated matched versus autologous transplantation in adult patients with good and intermediate risk acute myelogenous leukemia in first molecular remission.
Gorin NC, Labopin M, Pabst T, Remenyi P, Wu D, Huynh A, Volin L, Cahn JY, Yakoub-Agha I, Mercier M, Houhou M, Mohty M, Nagler A.
Am J Hematol. 2017 Sep 11. doi: 10.1002/ajh.24904. [Epub ahead of print]
PMID: 28960419

ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT.
Canaani J, Savani BN, Labopin M, Michallet M, Craddock C, Socié G, Volin L, Maertens JA, Crawley C, Blaise D, Ljungman PT, Cornelissen J, Russell N, Baron F, Gorin N, Esteve J, Ciceri F, Schmid C, Giebel S, Mohty M, Nagler A.
Am J Hematol. 2017 Aug;92(8):789-796. doi: 10.1002/ajh.24771. Epub 2017 Jun 9.
PMID: 28439910

Long-term follow-up of a retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic transplantation from matched related donors in myelodysplastic syndromes.
Martino R, Henseler A, van Lint M, Schaap N, Finke J, Beelen D, Vigouroux S, Alessandrino EP, Mufti GJ, Veelken JH, Bruno B, Yakoub-Agha I, Volin L, Maertens J, Or R, Leblond V, Rovira M, Kalhs P, Alvarez AF, Vitek A, Sierra J, Wagner E, Robin M, de Witte T, Kröger N.
Bone Marrow Transplant. 2017 Aug;52(8):1107-1112. doi: 10.1038/bmt.2017.19. Epub 2017 Mar 20.
PMID: 28319072

View all the EBMT publications on the website.

Bone Marrow Transplantation journal featured articles

Bone Marrow Transplantation
 publishes high quality, peer reviewed original research and reviews that address all aspects of basic biology and clinical use of haemopoietic cell transplantation.
The journal also covers all aspects of the research and treatment of transplant-related complications and consequences including quality of life and psychological issues. Basic research studies on topics of relevance are also covered.
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Read our pick of the latest articles …
Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT)
J R Passweg, H Baldomero et al.
Antibiotic-mediated modification of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation
J Whangbo, J Ritz & A Bhatt
GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes
Y-B Chen, T Wang et al.
Efficacy of host-dendritic cell vaccinations with or without minor histocompatibility antigen loading, combined with donor lymphocyte infusion in multiple myeloma patients
R Oostvogels, E Kneppers et al.
A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation
J Magenau, P Westervelt et al.
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*2016 Journal Citation Reports® Science Edition (Thomson Reuters, 2017)
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