Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission: An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation.
G Lucchini, et al. Biol Blood Marrow Transplant. 2016 Dec 1. pii: S10838791(16)305225. doi: 10.1016/j.bbmt.2016.11.022. [Epub ahead of print]
Allogeneic HCT remains the backbone of the treatment of children with high-risk acute myeloid leukemia (AML). However, given the smaller numbers of paediatric patients with this indication compared to adults, key questions of transplant methodology, in particular, the ideal preparative conditioning regimen, require additional research and evidence. In this important study, the Paediatric Diseases Working Party analyses a large population of over 600 children transplanted for AML in first complete remission between 2000 and 2010, with a focus on the impact of the conditioning regimen and HC source on the outcome: 458 sibling donors and 173 matched unrelated donors, 440 from bone marrow and 191 from peripheral blood, following conditioning with total body irradiation and cyclophosphamide (TBI-Cy; 190), busulfan-cyclophosphamide (BuCy; 389) or busulfan-cyclophosphamide-melphalan (BuCyMel; 133). Along with other interesting findings, such as a higher NRM, chronic GVHD and reduced LFS and OS in patients receiving peripheral blood HC, the main finding of this study is that patients receiving an intensified conditioning with busulfan-cyclophosphamide-melphalan had a significantly superior outcome than patients in the other cohorts. While NRM was comparable among groups, patients in the BuCyMel had a markedly reduced cumulative incidence of relapse at 5 years (14.7% vs 30-31.5%), which translated into improved LFS (74.5% vs 58-61.9%) and OS (76.6% vs 64-64.5%). Despite the intrinsic limitations of any retrospective registry analysis and the need for prospective confirmation, this study clearly suggests that paediatric patients receiving allogeneic HCT for AML in CR1 following the BuCyMel preparative regimen have reduced rates of relapse and superior outcomes.
Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.
M van Gelder, et al. Bone Marrow Transplant. 2016 Dec 12. doi: 10.1038/bmt.2016.282. [Epub ahead of print]
Decision-making for patients with high-risk CLL who are eligible for allogeneic HCT has become a challenge since the arrival of new kinase inhibitors and BCL2 inhibitors. The capacity of new drugs to maintain disease control for a few years with good treatment tolerability must be balanced against the possibility of long-term disease cure that at this point only allogeneic HCT offers. The EBMT activity survey shows a continuous reduction in HCT numbers in this indication in recent years. In this context, this new study by the Chronic Malignancies Working Party presents a novel analysis of long-term survival outcomes in a large population of 2589 patients with CLL who received an allogeneic HCT between 2000 and 2010, and uses landmark analyses and methods from relative survival analysis to calculate excess mortality compared general population. For the whole series, event-free survival, overall survival and non-relapse mortality 10 years after allo-HCT were 28%, 35% and 40%, respectively. For patients who were event-free at the five-year landmark, the subsequent five-year mortality was 8% for patients aged 45 years old and 45% for those aged 65 years old, compared with 3% and 14% in the age-, sex- and calendar year-matched general population, respectively. This study provides additional arguments in a compared analysis with the general population to suggest that long-term CLL-free survival remains an argument to consider allogeneic HCT for young patients with high-risk CLL. In addition, the findings provide arguments to promote improved long-term care for survivors. In particular, elderly patients may need special follow-up programs to counteract the increased risk of death compared to the general population.
Post-transplant cyclophosphamide versus antithymocyte-globulin as graft versus host disease prophylaxis in haploidentical transplant.
A Ruggeri, et al. Haematologica. 2016 Oct 6. pii: haematol.2016.151779. [Epub ahead of print]
The use of post-transplant high dose cyclophosphamide (PTCY) has facilitated the use of haploidentical donors for allogeneic HCT. Despite the marked increase in numbers of haploidentical HCT in recent years, most studies reported come from single centres and include several PTCY protocols for a variety of haematological malignancies. Despite the popularity, there is still no consensus on the optimal GVHD prophylaxis regimen in the setting of non T-cell depleted haploidentical HCT for particular indications. Thus, this study by the Acute Leukaemia Working Party aims to compare PTCY with ATG in 308 adult recipients of haploidentical HCT for AML, 193 with PTCY and 115 with ATG. Patients in the PTCY group had significantly less grade 3-4 acute GVHD (5%) than those in the ATG group (12%), similar rates of chronic GVHD, and a lower NRM (22% versus 30%, HR 1.77, 95%CI 1.09-2.86). Thus, PTCY led to better GVHD-free, relapse-free-survival (HR 1.45, 95% CI 1.04-2.02) and leukemia-free-survival (HR 1.48, 95% CI 1.03-
2.12) compared to ATG. Relapse rates were comparable in both strategies. Of note, centre experience was also associated with nonrelapse-mortality and GVHD-free, relapse-free survival. Despite the limitations of this retrospective analysis, and the unavailability of a prospective randomized trial, this registry study allows consistent results in a large number of patients, and strongly suggest that for patients with AML in CR, haploidentical HCT using PTCY with no ATG as GVHD prophylaxis leads to better LFS and GRFS, lower GVHD and lower NRM than ATG-based platforms, both using BM and PBSC and in the RIC and MAC setting.
The EBMT–ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis.
T Ruutu, et al. Bone Marrow Transplant. 2016 Nov 28. doi: 10.1038/bmt.2016.298. [Epub ahead of print]
The number of published guidelines and recommendations on various components of HCT is substantial but their impact and effects on transplantation strategies and real-life practice remain largely unknown. GvHD remains the major impediment to broader application of allogeneic HCT. Thus, in 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the EBMT and the European LeukemiaNet. Now, the CQLWP of the EBMT and the ELN present the results of a change-control analysis over those recommendations at all 341 EBMT allogeneic HCT centres. 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. The survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic HCT applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future. More importantly, this survey may serve as an example of the impact of recommendations or guidelines on clinical practice, and the usefulness of a change-control evaluation to obtain information about real-life working attitudes at HCT centres and to define the strategies to be followed.
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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.
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*2015 Journal Citation Reports® Science Edition (Thomson Reuters, 2016)