Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemiafree survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT. (Blood. 2012;120(2):473-476) IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment able to render patients with thalassemia major (TM) transfusion independent. 1-5 However, the clinical outcome after HSCT in children with TM who belong to class 3 of the Pesaro classification and in adults with poor performance status and/or organ dysfunction is still unsatisfactory because of the high risk of life-threatening complications or graft failure. [1][2][3][4][5] Treosulfan-based conditioning regimens have been shown initially to be safe and effective in adults with hematologic malignancies not eligible for conventional preparations. 6-9 These results have been confirmed recently in pediatric patients with high-risk hematologic malignancies receiving a treosulfan-based preparative regimen before second or third HSCT. 10 Moreover, a treosulfanbased conditioning regimen proved to be valuable in children with primary immunodeficiencies. 11 We reported recently preliminary, encouraging results on the use of a thiotepa/treosulfan/fludarabine myeloablative regimen in a cohort of 20 patients with TM. In particular, we found a high probability of cure of the disease in the absence of major transplantation-related complications in adults and in patients with poor performance status. 12 In the present study, we report the final results on the safety and efficacy of this regimen in a large cohort of TM patients. Details on patient, donor, and transplantation characteristics are reported in Table 1. Before transplantation, pediatric patients were assigned to 1 of the 3 classes of risk using the Pesaro classification. 1 Among 48 children, 27 were assigned to class 1, 17 to class 2, and 4 to class 3; the remaining 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling (matched family donor [MFD]) and the remaining 40 from an unrelated donor (UD). In the MFD cohort, the donor was always an HLA-identical sibling, and 11 patients received...

Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling.

BackgroundThalassemia is a common disorder worldwide with a predominant incidence in Mediterranean countries, North Africa, the Middle East, India, Central Asia, and Southeast Asia. Whilst substantial progress has been made towards the improvement of Health related quality of life (HRQoL) in western countries, scarce evidence-based data exists on HRQol of thalassemia children and adolescents living in developing countries.MethodsWe studied 60 thalassemia children from Middle Eastern countries with a median age of 10 years (range 5 to 17 years). HRQoL was assessed with the Pediatric Quality of Life Inventory (PedsQL) 4.0. The Questionnaire was completed at baseline by all patients and their parents. The agreement between child-self and parent-proxy HRQoL reports and the relationship between HRQoL profiles and socio-demographic and clinical factors were investigated.ResultsThe scores of parents were generally lower than those of their children for Emotional Functioning (mean 75 vs 85; p = 0.002), Psychosocial Health Summary (mean 70.3 vs 79.1; p = 0.015) and the Total Summary Score (mean 74.3 vs 77.7 p = 0.047). HRQoL was not associated with ferritin levels, hepatomegaly or frequency of transfusions or iron chelation therapy. Multivariate analysis showed that a delayed start of iron chelation had a negative impact on total PedsQL scores of both children (p = 0.046) and their parents (p = 0.007).ConclusionsThe PedsQL 4.0 is a useful tool for the measurement of HRQoL in pediatric thalassemia patients. This study shows that delayed start of iron chelation has a negative impact on children’s HRQoL.

Key Points• HRQoL and lifestyles of patients transplanted more than 20 years ago for thalassemia are similar to those of the general population.• Data on HRQoL in the long term provide both physicians and patients with a more complete picture of the advantages and potential risks of HSCT.The principal aim of our study was to investigate whether patients transplanted more than 20 years ago for b-thalassemia major had a different health-related quality of life (HRQoL) compared with the general population. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) were received from 109 ex-thalassemia patients who underwent hematopoietic stem cell transplantation (HSCT) during the 1980s and 1990s. Adjusted comparisons were performed separately for patient age at HSCT and the presence or absence of graft-versus-host disease (GVHD). Sociodemographic and clinical variables were also analyzed. The median age of our cohort at HSCT and the time of the survey was 12 years (range, 1-36) and 34 years (range, 21-48), respectively, with a median follow-up age of 22.8 years (range, 11.7-30.3). Statistical analysis of data collected more than 20 years after HSCT showed that the long-term HRQoL of ex-thalassemia patients was very similar to that of the general population. Clinical meaningful differences were only found for the general health (GH) scale (-8.9; 95% CI, -15.0 to 2.7, P 5 .005). Mental health, education level, employment status, marital status, living arrangements, and birth rate were compatible with normal living patterns. The development of GVHD and older age at transplantation were important impairing factors. Additional analyses performed to evaluate HRQoL in an age-sex-matched cohort of 124 patients receiving conventional treatment of b-thalassemia revealed poorer outcomes compared with the cohort of transplanted patients. (Blood. 2013;122(13):2262-2270

Summary The safety and efficacy of a preparation with treosulfan/thiotepa/fludarabine were explored in 20 thalassaemia patients given allogeneic marrow transplantation. Seventeen patients were transplanted from unrelated donors after receiving anti‐thymocyte globulin. The regimen was well tolerated. Two patients experienced secondary graft failure; one died of acute graft‐versus‐host disease. Cumulative incidence (95% confidence interval, CI) of transplantation‐related mortality and graft failure was 5% (95% CI, 0–34%) and 11% (95% CI, 3–43%), respectively. Two‐year probability of survival and thalassaemia‐free survival was 95% (95% CI, 85–100%) and 85% (95% CI, 66–100%), respectively. This regimen might find elective application in patients at high risk of developing life‐threatening complications.