EBMT NEWSLETTER | June 2016 | Volume 52 - Issue 3

Important dates
Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT.
DeFilipp Z, Duarte RF, Snowden JA, Majhail NS, Greenfield DM, Miranda JL, Arat M, Baker KS, Burns LJ, Duncan CN, Gilleece M, Hale GA, Hamadani M, Hamilton BK, Hogan WJ, Hsu JW, Inamoto Y, Kamble RT, Lupo-Stanghellini MT, Malone AK, McCarthy P, Mohty M, Norkin M, Paplham P, Ramanathan M, Richart JM, Salooja N, Schouten HC, Schoemans H, Seber A, Steinberg A, Wirk BM, Wood WA, Battiwalla M, Flowers ME, Savani BN, Shaw BE; CIBMTR Late Effects and Quality of Life Working Committee and the EBMT Complications and Quality of Life Working Party.
Biol Blood Marrow Transplant. 2016 May 14. pii: S1083-8791(16)30079-9. doi: 10.1016/j.bbmt.2016.05.007. [Epub ahead of print]
This important cooperative project by the EBMT Complications and Quality of Life Working Party and the CIBMTR Late Effect and Quality of Life Working Committee draws a comprehensive review of Metabolic Syndrome after hematopoietic cell transplantation (HCT) and provides practical recommendations for management. Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of HCT have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. The authors of EBMT and CIBMTR deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the Severe Aplastic Anemia Working Party of EBMT.
Devillier R, Dalle JH, Kulasekararaj A, D' Aveni M, Clément L, Chybicka A, Vigouroux S, Chevallier P, Koh M, Bertrand Y, Michallet M, Zecca M, Yakoub-Agha I, Cahn JY, Ljungman P, Bernard M, Loiseau P, Dubois V, Maury S, Socié G, Dufour C, Peffault de Latour R.
Haematologica. 2016 Apr 7. pii: haematol.2015.138727. [Epub ahead of print]
Unrelated HCT for severe aplastic anemia is currently recommend for patients who failed immunosuppressive therapy. However, the results of unrelated SCT for AA have improved in recent years. In this article, the EBMT Severe Aplastic Anemia Working Party and the French Society of Bone Marrow Transplantation and Cell Therapies develop a simple score to predict outcome of patients who undergo unrelated HCT for aplastic anemia.
Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. They analyzed patients (n=139) from the French registry who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age > 30 years (Hazard Ratio=2.39; p=0.011), time from diagnosis to transplantation > 12 months (Hazard Ratio=2.18; p=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; p=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, they built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; p < 0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; p=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.
Reduced intensity allogeneic stem cell transplantation for follicular lymphoma relapsing after an autologous transplant achieves durable long term disease control. An analysis from the Lymphoma Working Party of the EBMT.
Robinson SP, Boumendil A, Finel H, Schouten H, Ehninger G, Maertens J, Crawley C, Rambaldi A, Russell N, Anders W, Blaise D, Yakoub-Agha I, Ganser A, Castagna L, Volin L, Cahn JY, Montoto S, Dreger P.
Ann Oncol. 2016 Mar 8. pii: mdw124. [Epub ahead of print]
Patients with follicular lymphoma (FL) relapsing after an autologous HCT may be treated with a variety of therapies including a reduced intensity allogeneic HCT (RICalloHCT). In this study, the Lymphoma Working Party of the EBMT conducted a retrospective analysis of a large cohort of patients undergoing RICalloHCT for FL in this setting: 183 patients, median age 45 years (range 21-69), had undergone an autologous HCT at a median of 30 months prior to the RICalloHCT. Before the RICalloHCT they had received a median of 4 lines (range 3-10) of therapy and 81% of patients had chemo-sensitive disease and 16% had chemo-resistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%).With a median follow up of 59 months the non-relapse mortality was 27% at 2 years. The median remission duration after autologous HCT and RICalloHCT were 14 and 43 months respectively. The 5-year relapse/progression rate, progression free survival and overall survival were 16%, 48% and 51% respectively and were associated with age and disease status at RICalloHCT. The authors concluded that this data suggests that a RICalloHCT is an effective salvage strategy in patients with FL recurring after a prior autologous HCT and might overcome the poor prognostic impact of early relapse after autologous HCT.
Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT.
Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, Schwerdtfeger R, Bunjes D, Glass B, Socié G, Ljungman P, Craddock C, Baron F, Ciceri F, Gorin NC, Esteve J, Schmid C, Giebel S, Mohty M, Nagler A.
Haematologica. 2016 Jun;101(6):773-80. doi: 10.3324/haematol.2015.138180. Epub 2016 Mar 11
Because of the inherent therapy related morbidity and mortality, an upper age limit for allogeneic HCT is a matter of debate, in particular if only mismatch donors are available.  Furthermore, it is unknown whether older patient can tolerate a more intensive conditioning regimen. For this reason, the Acute leukemia Working party of EBMT conducted a retrospective study addressing this issue. Eight hundred and eighty three patients with acute leukemia receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. This EBMT study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors. 

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party.
Sobh M, Michallet M, Gahrton G, Iacobelli S, van Biezen A, Schönland S, Petersen E, Schaap N, Bonifazi F, Volin L, Meijer E, Niederwieser D, El-Cheikh J, Tabrizi R, Fegeux N, Finke J, Bunjes D, Cornelissen J, Einsele H, Bruno B, Potter M, Fanin R, Mohty M, Garderet L, Kröger N.
Leukemia. 2016 May 20. doi: 10.1038/leu.2016.101. [Epub ahead of print]
The role of allogeneic HCT in Multiple Myeloma (MM) is not well defined. In particular for relapsed patients, data from prospective studies are very limited. In this descriptive analysis, the EBMT Chronic Malignancies Working Party describes the use and outcomes of allogeneic HCT for MM in Europe between January 1990 and December 2012. The study includes 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. There are three groups: (1) allogeneic HCT upfront (n=1924), (2) tandem autologous-allogeneic HCT (n=2004) and (3) allogeneic HCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allogeneic HCT over the years. Upfront allogeneneic HCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem autologous-allogeneic HCT peaked around year 2004 and contributed to 19% of allogeneic HCTs in 2012. Allogeneic HCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allogeneic HCTs in 2012. Remarkable heterogeneity in using allogeneic HCT was observed among the different European countries. The 5-year survival probabilities from time of allogeneic HCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allogeneic HCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allogeneic HCT as salvage therapy for MM.

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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.

2015 Impact Factor 3.636*
*2015 Journal Citation Reports® Science Edition (Thomson Reuters, 2016)
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Acute kidney injury in HCT: an update
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