Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022
Snowden JA, et al, on behalf of the EBMT
Bone Marrow Transplant. 2022 Aug.
Every several years, the EBMT Board and Scientific Council has published updated ‘guidelines’ for HSCT to reflect current practice and help support centres, their clinicians, MDTs and broader health services define indications for transplantation. This recent publication (the 8th) uses the same system harnessing the expertise of the EBMT working parties to substantially update the previous excellent 2019 indications (Duarte et al) with a number of significant additions, namely the first reference to CART therapies in some indications. In this broad-based document, the text attempts to balance transplant options against non-HCT strategies, whilst the detailed adult and paediatric tables provide an indication via the EBMT-style grading of evidence based of the strength of recommendations. There is inevitably reference to the now ever-present threat of Covid-19 and need to maintain quality in clinical practice via local MDT working, whilst maintaining JACIE accreditation and participation in the EBMT Benchmarking exercise. Over the years, along with the EBMT Surveys and EBMT Handbooks, this ‘Indications’ paper has been one of the cornerstones and ‘cross-cutting’ outputs of EBMT. As the fields of HSCT and cellular therapy are becoming more complex, EBMT are currently considering how best to work to standardise and harmonise clinical practice in response to emerging evidence. For the time being, the broad-reaching ‘Indications’ paper remains an invaluable state-of -the-art resource and a basis for future guidelines in more specialised areas of practice.
Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modelling
Lawless S, et al, on behalf of CMWP.
Haematologica. 2022 Jun 30.
Clinical decision making is challenging in primary plasma cell leukaemia, which remains a poor prognosis plasma cell neoplasm despite the significant advances in anti-plasma cell therapies in myeloma and other related conditions. In younger patients transplant approaches are commonly employed but the ideal strategy remains unclear. With the aim of supporting clinical decision making in this difficult area of practice, the CMWP undertook the largest ever retrospective analysis of HSCT in primary plasma cell leukaemia using the EBMT registry data for patients treated from 1998 to 2014. In this analysis, 751 patients with primary plasma cell leukaemia were divided into 1 of 4 transplant strategies a) ‘single auto-first’ HSCT; b) ‘single allo-first’ HSCT; c) ‘tandem auto-allo’ HSCT; or d) ‘tandem auto-auto’ HSCT. Specialised statistical methods were used to avoid time and other biases given the long study eligibility interval. The initial breakdown of analysis focussed on patients undergoing ‘single allo-first’ (n=70) versus ‘single auto-first’ HSCT (n=681), regardless of whether there was subsequent second transplant. The ‘single allo-first’ group had lower relapse rate (45.9% vs. 68.4%) but was disadvantaged by substantially higher 3-year NRM (27% vs 7.3%). In contrast ‘tandem auto-allo’ transplantation (n=122) was followed by significant benefit in progression free survival post-100 days compared to ‘single auto’ (p=0.012) without significantly increased risk in the short term. ‘Tandem auto-auto’ (n=117) was an effective option for patients achieving CR prior to first transplant, whereas in patients without CR prior to transplant the model predicted that ‘tandem auto-allo’ was superior. Given the significant early mortality risk of up-front ‘allo-first’ HSCT, the data support tandem transplant strategies are superior, for which remission status can be considered alongside risks in individualised decision making with respect to choose of tandem transplant type. As well as supporting clinical decision making, this large retrospective study provides a basis for further studies in this challenging, poor prognosis group of patients in the modern era of plasma cell disease management.
Impact of the Addition of Antithymocyte Globulin to Post-Transplantation Cyclophosphamide in Haploidentical Transplantation with Peripheral Blood Compared to Post-Transplantation Cyclophosphamide Alone in Acute Myelogenous Leukemia: A Retrospective Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Battipaglia G, et al on behalf of ALWP.
Transplant Cell Ther. 2022 Jun 14.
Post-transplant cyclophosphamide (PTCy), as pioneered by the team at Johns Hopkins and others, has been remarkable in that it has not only revolutionised the practice of allogeneic HSCT, particularly enabling the evolution of haplo-identical transplantation, but also, it’s been achieved with an old drug ‘re-purposed’ in the modern era – a old dog with new tricks!
However, can we make it better by building on the success?
This interesting retrospective study from the ALWP included 441 patients treated between 2011-19 who underwent a first haploidentical HCT with PBSC for AML in CR1 or CR2. The largest comparator group used PTCy as the backbone for GVHD prophylaxis (n=374), and were compared with ATG + PTCy (with both groups receiving ciclosporin and MMF). Despite the differences in size, the groups were otherwise reasonably balanced with a median age of 56 and year of haplo-identical HCT of 2017, with similar levels of the more commonly used RIC versus full intensity conditioning, similar engraftment dynamics, length of follow up and no significant differences on univariate analysis between the groups for important variables. However, on multivariate analysis, the addition of ATG was associated with a lower risk of chronic GVHD (p= 0.03) without any other differences in survival, relapse incidence and TRM. The study supports the feasibility and potential benefits of adding ATG to haplo-indentical conditioning regimens and supports more formal evaluation in a prospective setting, where key long-term survival, GFRS, and HRQoL/PROMs, and health economic and other endpoints that may be affected by a lesser incidence and severity of chronic GVHD, can be carefully measured.