EBMT NEWSLETTER | September 2017 | Volume 58 - Issue 4

Important dates

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

Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.
Martínez C, Gayoso J, Canals C, Finel H, Peggs K, Dominietto A, Castagna L, Afanasyev B, Robinson S, Blaise D, Corradini P, Itälä-Remes M, Bermúdez A, Forcade E, Russo D, Potter M, McQuaker G, Yakoub-Agha I, Scheid C, Bloor A, Montoto S, Dreger P, Sureda A; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol. 2017 Aug 28:JCO2017726869. doi: 10.1200/JCO.2017.72.6869. [Epub ahead of print] PMID: 28846465

In this high ranked EBMT publication of the Lymphoma Working Party the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation was compared to the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). 709 adult patients with Hodgkin lymphoma who were registered in EBMTdatabase who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation were included. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). The LWP  concluded that Post-transplantation cyclophosphamide-based HAPLO transplantation results in lowedr cGvHD and similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation.
Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, Dignan F, Gibson B, Guengoer T, Gruhn B, Lankester A, Locatelli F, Pagliuca A, Peters C, Richardson PG, Schulz AS, Sedlacek P, Stein J, Sykora KW, Toporski J, Trigoso E, Vetteranta K, Wachowiak J, Wallhult E, Wynn R, Yaniv I, Yesilipek A, Mohty M, Bader P.
Bone Marrow Transplant. 2017 Jul 31. doi: 10.1038/bmt.2017.161. [Epub ahead of print] PMID: 28759025

In this position paper , members of EBMT developed and proposed  new diagnostic and severity criteria for SOS/VOD in children.  Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children.

Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT).
Schetelig J, de Wreede LC, Andersen NS, Moreno C, van Gelder M, Vitek A, Karas M, Michallet M, Machaczka M, Gramatzki M, Beelen D, Finke J, Delgado J, Volin L, Passweg J, Dreger P, Schaap N, Wagner E, Henseler A, van Biezen A, Bornhäuser M, Iacobelli S, Putter H, Schönland SO, Kröger N; CLL subcommittee, Chronic Malignancies Working Party.
Br J Haematol. 2017 Aug;178(4):521-533. doi: 10.1111/bjh.14791. Epub 2017 Jun 7.
In this paper from the Chronic Malignancies Working Party (CMWP) the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study fro CLL patients who received allogeneic SCT was evaluated. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%). Larger numbers of CLL alloHCTs (hazard ratio [HR] 0·96, P = 0·002), certification of quality management (HR 0·7, P = 0·045) and a higher gross national income per capita (HR 0·4, P = 0·04) improved EFS. In vivo T-cell depletion (TCD) with alemtuzumab compared to no TCD (HR 1·5, P = 0·03), and a female donor compared to a male donor for a male patient (HR 1·4, P = 0·02) had a negative impact on EFS, but not non-myeloablative versus more intensive conditioning. After correcting for patient-, procedure- and centre-characteristics, significant variation in centre outcomes persisted. In conclusion, further research on the impact of centre and procedural characteristics is warranted. Non-myeloablative conditioning appears to be the preferable approach for patients with CLL.

Salvage high-dose chemotherapy in female patients with relapsed/refractory germ-cell tumors: a retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT).
De Giorgi U, Richard S, Badoglio M, Kanfer E, Bourrhis JH, Nicolas-Virelizier E, Vettenranta K, Lioure B, Martin S, Dreger P, Schuler MK, Thomson K, Scarpi E, Rosti G, Selle F, Mangili G, Lanza F, Bregni M; Solid Tumours Working Party (STWP) of the EBMT.
Ann Oncol. 2017 Aug 1;28(8):1910-1916. doi: 10.1093/annonc/mdx259.
PMID: 28510616

In this retrospective study of the Solid Tumor Working Party, outcome of high-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation was studied in female patients with germ cell tumors. Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). The authors concluded that salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT.

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.
Visit new website - https://www.nature.com/bmt/
2016 Impact Factor 3.874*
Average time to first decision without external review = 7 days
Average time to first decision following external review = 32 days
Average time to online publication  = 23 days
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Read our pick of the latest articles …
One or two umbilical cord blood cell units? Caveat emptor
J Sanz & R P Gale
Antibiotic-mediated modification of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation
J Whangbo, J Ritz & A Bhatt
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
Halfway there: the past, present and future of haploidentical transplantation
M Slade, B Fakhri et al
Next-generation sequencing indicates false-positive MRD results and better predicts prognosis after SCT in patients with childhood ALL
M Kotrova, V H J van der Velden et al
Routine vaccination practice after adult and paediatric allogeneic haematopoietic stem cell transplant: a survey of UK NHS programmes
P D E Miller, T I de Silva et al
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*2016 Journal Citation Reports® Science Edition (Thomson Reuters, 2017)

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