Dataset Information

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

ABSTRACT: In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient's age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.

SUBMITTER: Rahal I

PROVIDER: S-EPMC6029533 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

Rahal Ilhem I Galambrun Claire C Bertrand Yves Y Garnier Nathalie N Paillard Catherine C Frange Pierre P Pondarré Corinne C Dalle Jean Hugues JH de Latour Regis Peffault RP Michallet Mauricette M Steschenko Dominique D Moshous Despina D Lutz Patrick P Stephan Jean Louis JL Rohrlich Pierre Simon PS Yakoub-Agha Ibrahim I Bernaudin Françoise F Piguet Christophe C Aladjidi Nathalie N Badens Catherine C Berger Claire C Socié Gérard G Dumesnil Cécile C Castex Marie Pierre MP Poirée Marilyne M Lambilliotte Anne A Thomas Caroline C Simon Pauline P Auquier Pascal P Michel Gérard G Loundou Anderson A Agouti Imane I Thuret Isabelle I

Haematologica 20180329 7

In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant fro ...[more]

PMID: 29599204

Similar Datasets

Project description:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective curative intervention for children with β-thalassemia major (β-TM). They are susceptible to growth disorders due various factors. The primary objective of this study was to investigate the growth and development of children with β-TM both before and after undergoing allo-HSCT during a one-year follow-up period.MethodsAccording to the international reference standards for child growth established by the World Health Organization in 2006, participants were divided into two groups based on their Z scores: weight-for-age Z scores (WAZ), height-for-age Z scores (HAZ), and body mass index-for-age Z scores (BAZ) before allo-HSCT. The first group included children with normal nutritional levels (-2≤ Z scores ≤2), while the second group consisted of children with malnutrition (Z scores <-2 or >2). Measurements of weight, height, and body mass index (BMI) were recorded at six time points: prior to allo-HSCT (T0), and 1 month (T1), 3 months (T3), 6 months (T6), 9 months (T9), and 12 months (T12) following the procedure.ResultsAmong the 56 children diagnosed with β-TM, 25% were malnourished prior to HSCT. In the group with normal nutrition, mean WAZ (P=0.04) and HAZ (P<0.001) values were significantly higher at T12 compared to T0; however, mean BAZ was similar at T12 and T0 (P=0.61). In contrast, in the malnutrition group, no significant differences were observed in mean WAZ (P=0.12), HAZ (P=0.27), or BAZ (P=0.75) values between T12 and T0. Notably, the incidence of increased HAZ was significantly more prevalent in children aged seven years or younger than in those older than seven years (P=0.01).ConclusionsChildren diagnosed with β-TM who had normal nutritional levels at the time of allo-HSCT showed significant growth improvements within one year of follow-up compared to their pre-transplantation state. Additionally, the age at which allo-HSCT was performed may substantially influence post-transplantation growth rates. Regular monitoring of growth and development from the time of diagnosis is crucial to ensure optimal nutritional status at the time of allo-HSCT, thereby enhancing the prognosis for these children after transplantation.

Project description:A toxicity-reduced conditioning regimen with treosulfan, fludarabine, and thiotepa in patients with high-risk β-thalassemia major has significantly improved hematopoietic stem cell transplantation (HCT) outcomes. However, complications resulting from regimen-related toxicities (RRTs), mixed chimerism, and graft rejection remain a challenge. We evaluated the dose-exposure-response relationship of treosulfan and its active metabolite S, S-EBDM, in a uniform cohort of patients with β-thalassemia major to identify whether therapeutic drug monitoring (TDM) and dose adjustment of treosulfan is feasible. Plasma treosulfan/S, S-EBDM levels were measured in 77 patients using a validated liquid chromatography with tandem mass spectrometry method, and the pharmacokinetic parameters were estimated using nlmixr2. The influence of treosulfan and S, S-EBDM exposure, and GSTA1/NQO1 polymorphisms on graft rejection, RRTs, chimerism status, and 1-year overall survival (OS), and thalassemia-free survival (TFS) were assessed. We observed that treosulfan exposure was lower in patients with graft rejection than those without (1,655 vs. 2,037 mg•h/L, P = 0.07). Pharmacodynamic modeling analysis to identify therapeutic cutoff revealed that treosulfan exposure ≥1,660 mg•hour/L was significantly associated with better 1-year TFS (97% vs. 81%, P = 0.02) and a trend to better 1-year OS (90% vs. 69%, P = 0.07). Further, multivariate analysis adjusting for known pre-HCT risk factors also revealed treosulfan exposure <1,660 mg•h/L (hazard ratio (HR) = 3.23; 95% confidence interval (CI) = 1.12-9.34; P = 0.03) and GSTA1*B variant genotype (HR = 3.75; 95% CI = 1.04-13.47; P = 0.04) to be independent predictors for inferior 1-year TFS. We conclude that lower treosulfan exposure increases the risk of graft rejection and early transplant-related mortality affecting TFS. As no RRTs were observed with increasing treosulfan exposure, TDM-based dose adjustment could be feasible and beneficial.

Project description:PurposeTo analyze factors influencing tacrolimus (TAC) trough concentration (C0) in β-thalassemia major (β-TM) pediatric patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and to investigate the effects of genotype polymorphism and drug-drug interactions on TAC trough concentration in children with β-TM. Furthermore, to analyze the correlation between TAC C0 and efficacy and adverse reactions.Patients and methodsProspectively collection of demographic information and details of combined treatment of patients with β-TM receiving HSCT, and genotypes of CYP3A4, CYP3A5, and ABCB1 (rs1045642, rs1128503, rs2032582) were obtained for each patient. Univariate analysis and multiple linear regression analysis were used to investigate influencing factors on TAC C0. The impact of different genotypes and the co-administration of azole antifungal drugs on β-TM patients receiving TAC were evaluated, together with the correlation between acute graft-versus-host disease (aGVHD), infection, and liver injury of TAC C0.ResultsA total of 46 patients with 587 concentration data were included. The multiple linear regression results showed that the patient's sex, weight, postoperative time, hemoglobin, platelet count, serum cystatin C, and combined voriconazole were independent influencing factors of the infusion trough concentration/daily dose, C0/Div. Age, body surface area, postoperative time, co-administration of voriconazole, and CYP3A4*18B are independent influencing factors of C0/Dpo. Group comparisons showed that voriconazole can affect TAC C0 administered intravenously (IV) and orally in β-TM pediatric patients, while patient genotype can affect TAC C0 during oral administration. TAC C0 does not correlate with aGVHD or liver injury, but infection may be associated with TAC C0.ConclusionThe concentration of TAC should be closely monitored when co-administered with voriconazole. It is worth considering that the influence of genotype on the trough concentration of oral TAC and individualized drug administration warrant investigation. Finally, this study indicated that C0 is not suitable as an indicator of the efficacy of TAC.

Project description:BackgroundHepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major.MethodsBetween April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time.ResultsThe 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs.ConclusionsBased on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.

Dataset Information

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

Publications

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets