Dataset Information

Pre-transplantation Risks and Transplant-Techniques in Haematopoietic Stem Cell Transplantation for Acute Leukaemia.

ABSTRACT: Background:The role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres. Methods:This Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50?years; 1-75?years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N?=?8641; 95%) or matched unrelated donor (N?=?462; 5%) for acute myeloid (N?=?6432; 71%) or acute lymphoblastic (N?=?2671; 29%) leukaemia in first complete remission, and reported by 240 centres in 30 countries to the benchmark database of the European Society for Blood and Marrow Transplantation (EBMT) searched for factors associated with use of transplant techniques (standard N?=?6375;70% or reduced intensity conditioning N?=?2728;30%, respectively bone marrow N?=?1945;21% or peripheral blood N?=?7158;79% as stem cell source), and their impact on outcome. Findings:Treatment groups differed significantly from baseline population (p?

SUBMITTER: Gratwohl A

PROVIDER: S-EPMC6833359 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Pre-transplantation Risks and Transplant-Techniques in Haematopoietic Stem Cell Transplantation for Acute Leukaemia.

Gratwohl Alois A Duarte Rafael R Snowden John A JA van Biezen Anja A Baldomero Helen H Apperley Jane J Cornelissen Jan J Greinix Hildegard T HT Grath Eoin Mc EM Mohty Mohamad M Kroeger Nicolaus N Nagler Arnon A Niederwieser Dietger D Putter Hein H Brand Ronald R

EClinicalMedicine 20190809

<h4>Background</h4>The role of conditioning intensity and stem cell source on modifying pre-transplantation risk in allogeneic haematopoietic stem cell transplantation (HSCT) is a matter of debate, but crucial when benchmarking centres.<h4>Methods</h4>This Retrospective, multicenter exploratory-validation analysis of 9103 patients, (55.5% male, median age 50 years; 1-75 years range) with an allogeneic HSCT between 2010 and 2016 from a matched sibling (N = 8641; 95%) or matched unrelated donor (N ...[more]

PMID: 31709412

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Project description:Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy is subject to radiobiological trade-offs between ALL cell destruction, immune and haematopoietic stem cell survival, and various adverse effects in normal tissue. To diminish toxicity, a shift from single-fraction to fractionated TBI has taken place. However, HSCT and TBI are still associated with multiple late sequelae, leaving room for improvement. This review discusses the past developments of TBI and considerations for dose, fractionation and dose-rate, as well as issues regarding TBI setup performance, limitations and possibilities for improvement. TBI is typically delivered using conventional irradiation techniques and centres have locally developed heterogeneous treatment methods and ways to achieve reduced doses in several organs. There are, however, limitations in options to shield organs at risk without compromising the anti-leukaemic and immunosuppressive effects of conventional TBI. Technological improvements in radiotherapy planning and delivery with highly conformal TBI or total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI) have opened the way to investigate the potential reduction of radiotherapy-related toxicities without jeopardising efficacy. The demonstration of the superiority of TBI compared with chemotherapy-only conditioning regimens for event-free and overall survival in the randomised For Omitting Radiation Under Majority age (FORUM) trial in children with high-risk ALL makes exploration of the optimal use of TBI delivery mandatory. Standardisation and comprehensive reporting of conventional TBI techniques as well as cooperation between radiotherapy centres may help to increase the ratio between treatment outcomes and toxicity, and future studies must determine potential added benefit of innovative conformal techniques to ultimately improve quality of life for paediatric ALL patients receiving TBI-conditioned HSCT.

Project description:BACKGROUND:Mannose-binding lectin (MBL) is a key component of innate immunity. Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection. The aim of this work was to analyse the incidence and severity of infections and mortality in relation to the MBL2 genotype and MBL levels in patients underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT). RESULTS:This was a prospective cohort study of 72 consecutive patients underwent Allo-HSCT between January 2007 and June 2009 in a tertiary referral centre. Three periods were considered in the patients' follow-up: the early period (0-30?days after Allo-HSCT), the intermediate period (30-100?days after Allo-HSCT) and the late period (>?100?days after Allo-HSCT). A commercial line probe assay for MBL2 genotyping and an ELISA Kit were used to measure MBL levels. A total of 220 episodes of infection were collected in the 72 patients. No association between donor or recipient MBL2 genotype and infection was found. The first episode of infection presented earlier in patients with pre-transplant MBL levels of <?1000?ng/ml (median 6d vs 8d, p?=?0.036). MBL levels <?1000?ng/ml in the pre-transplant period (risk ratio (RR) 2.48, 95% CI 1.00-6.13), neutropenic period (0-30?days, RR 3.28, 95% CI 1.53-7.06) and intermediate period (30-100?days, RR 2.37, 95% CI 1.15-4.90) were associated with increased risk of virus infection. No association with bacterial or fungal disease was found. Mortality was associated with pre-transplant MBL levels <?1000?ng/ml (hazard ratio 5.55, 95% CI 1.17-26.30, p?=?0.03) but not with MBL2 genotype. CONCLUSIONS:Patients who underwent Allo-HSCT with low pre-transplant MBL levels presented the first episode of infection earlier and had an increased risk of viral infections and mortality in the first 6?months post-transplant. Thus, pre-transplant MBL levels would be important in predicting susceptibility to viral infections and mortality and might be considered a biomarker to be included in the pre-transplantation risk assessment.

Dataset Information

Pre-transplantation Risks and Transplant-Techniques in Haematopoietic Stem Cell Transplantation for Acute Leukaemia.

Publications

Pre-transplantation Risks and Transplant-Techniques in Haematopoietic Stem Cell Transplantation for Acute Leukaemia.

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