Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Abstract

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...

Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases

“…5,6,9,14,20,21 In this retrospective EBMT study, we evaluated the toxicity profile and outcome of 316 patients with non-malignant diseases undergoing HSCT, following treosulfan-based conditioning. To our knowledge, this is the largest such study to date.…”

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

“…11 Subsequently, several centers worldwide have started their own transplant programs. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Recent results show that, with modern transplantation approaches, and careful patient selection, even better results could be obtained (Table 2). At the same time, however, survival without transplantation of TM patients has improved as the result both of a better understanding of the pathophysiology of iron overload and improvements in the medical therapy of TM; survival into the fourth or fifth decade of life is now possible for well-treated patients.…”

“…14, 16 Particularly fludarabine has been included in the conditioning regimen by several groups in the last decade with low TRM and reduced rejection risk (Table 2).…”

Conditioning regimens in allo-SCT for thalassemia major

“…Recently, the same group reported on their expanded experience with this reduced-toxicity myeloablative regimen. 28 In this expanded series of 60 cases with thalassemia major, the median age was 7 years, although only 7% of the 48 children were Class III and the remaining 12 were adults. Forty (67%) patients received an unrelated donor transplant.…”