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Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.

ABSTRACT: Acute leukaemia or advanced myelodysplastic syndrome (MDS ? 5% blasts) in Fanconi anaemia (FA) patients is associated with a poor prognosis. We report 21 FA patients with acute leukaemia or advanced MDS who underwent haematopoietic cell transplantation (HCT) at the University of Minnesota between 1988 and 2011. Six patients had biallelic BRCA2 mutations. Eight patients received pre-transplant cytoreduction, with 3 achieving complete remission. HCT donor source included human leucocyte antigen-matched sibling (n = 2) or alternative donors (n = 19). Neutrophil engraftment was 95% for the entire cohort, and the incidence of acute graft-versus-host disease was 19%. 5-year overall survival (OS) was 33%, with a relapse rate of 24%, with similar OS in patients with biallelic BRCA2 mutations. Our study supports the use of HCT in the treatment of FA patients with acute leukaemia or advanced MDS, however, the role of chemotherapy prior to HCT remains unclear for this population. FA patients with biallelic BRCA2 are unique and may benefit from higher dose chemotherapy relative to other complementation groups.

SUBMITTER: Mitchell R

PROVIDER: S-EPMC4060801 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.

Mitchell Richard R Wagner John E JE Hirsch Betsy B DeFor Todd E TE Zierhut Heather H MacMillan Margaret L ML

British journal of haematology 20131030 3

Acute leukaemia or advanced myelodysplastic syndrome (MDS ≥ 5% blasts) in Fanconi anaemia (FA) patients is associated with a poor prognosis. We report 21 FA patients with acute leukaemia or advanced MDS who underwent haematopoietic cell transplantation (HCT) at the University of Minnesota between 1988 and 2011. Six patients had biallelic BRCA2 mutations. Eight patients received pre-transplant cytoreduction, with 3 achieving complete remission. HCT donor source included human leucocyte antigen-ma ...[more]

PMID: 24172081

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Project description:BackgroundThe 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.MethodsThis 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.FindingsTreatment groups differed significantly from baseline population (p < 0.001), and within groups regarding patient-, disease-, donor-, and centre-related pre-transplantation risk factors (p < 0.001); choice of technique did depend on pre-transplantation risk factors and centre (p < 0.001). Probability of overall survival at 5 years decreased systematically and significantly with increasing pre-transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1-1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3-1·7], p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6-2·2], p < 0.001) with no significant differences between treatment groups (likelihood ratio test on interaction: p = 0.40). Overall survival was significantly associated with selection steps and completeness of information (p < 0.001).InterpretationPatients' pre-transplantation risk factors determine survival, independent of transplant techniques. Transplant techniques should be regarded as centre policy, not stratification factor in benchmarking. Selection criteria and completeness of data bias outcome. Outcomes may be improved more effectively through better identifying pre-transplantation factors as opposed to refinement of transplant techniques.FundingThe study was funded by EBMT.

Project description:ObjectivesAcute myeloid leukaemia (AML) and high-risk myelodysplastic syndromes (MDS) are often treated with intensive chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT). The pretransplant treatment results in a general deterioration of the patient's health and quality of life. Furthermore, allo-HSCT can be responsible for significant toxicity with risks of graft-versus-host disease (GvHD). Developing strategies to prevent physical deconditioning, undernutrition and psychological distress could help maintain a satisfactory general state of health before transplantation and thus limit these deleterious effects. This protocol evaluates the feasibility and adherence to a personalised prehabilitation programme, which can be modulated and assisted by connected objects, provided from the diagnosis to the allo-HSCT.Methods and analysisThis multicentre interventional study will include 50 patients treated for AML or high-risk MDS with intensive chemotherapy and eligible for allo-HSCT. The intervention consists of a coached, supervised or self-directed physical activity programme, organised during the hospitalisation phases and periods at home. At the same time, patients will receive a weekly dietary follow-up. The whole intervention is controlled and modulated through the use of a dedicated application and connected objects allowing adaptation and individualisation. The rate of participation in the prescribed physical activity sessions will assess the feasibility of this study. In addition, the evolution of physical capacities (Short Physical Performance Battery, grip and quadriceps strengths), psychosocial parameters (Functional Assessment of Cancer Therapy - Leukaemia, Functional Assessment of Cancer Therapy - Fatigue, subjective well-being, Hospital Anxiety and Depression Scale, self-efficacy, Coach-Athlete Relationship Questionnaire, interviews) and clinical status (weight, lean body mass, survival rate, number of infections, days of hospitalisation, GvHD) will be evaluated.Ethics and disseminationThe study procedures have been approved by the National Ethics Committee (21.00223.000003). Consent is given in person by each participant. The information collected on the participants contains only a non-identifiable study identifier. The results of this protocol will be published in a scientific paper and communicated to the medical staff of the medical centre.Trial registration numberNCT03595787.

Dataset Information

Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.

Publications

Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia.

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