Long‐term survival of beta thalassemia major patients treated with hematopoietic stem cell transplantation compared with survival with conventional treatment

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) in thalassemia remains a challenge. We reported a single-centre case-control study of a large cohort of 516 children and adult patients treated with HSCT or blood transfusion support and iron chelation therapy; 258 patients (median age 12, range 1-45) underwent sibling (67%) or unrelated (33%) HSCT; 97 patients were adults (age ≥ 16 years). The median follow-up after HSCT was 11 years (range 1-30). The conditioning regimen was busulfan (80.6%) or treosulfan-based (19.4%). A cohort of 258 age-sex matched conventionally treated (CT) patients was randomly selected. In transplanted patients the 30-year overall survival (OS) and thalassemia-free survival (TFS) were 82.6 ± 2.7% and 77.8 ± 2.9%, compared to the OS of 85.3 ± 2.7% in CT patients (P = NS); The incidence of grade II-IV acute and chronic graft versus host disease (GvHD) was 23.6% and 12.9% respectively. The probability of rejection was 6.9%. Transplant-related mortality (TRM) (13.8%) was similar to the probability of dying of cardiovascular events in CT patients (12.2%). High-risk Pesaro score (class 3) was associated with lower OS (OR = 1.99, 95% C.I.=1.31-3.03) and TFS (OR = 1.54, 95% C.I.=1.12-2.12). In adult patients, the 23-years OS and TFS after HSCT were 70 ± 5% and 67.3 ± 5%, compared to 71.2 ± 5% of OS in CT (P = NS). Finally, treosulfan was associated with lower risk of acute GvHD (P = .004; OR = 0.28, 95% C.I.=0.12-0.67). In conclusion, the 30-year survival rate of ex-thalassemia patients after HSCT was similar to that expected in CT thalassemia patients, with the vast majority of HSCT survivors cured from thalassemia.

The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation

“…To this end, allogenic hematopoietic stem cell transplantation also represents a reasonable standard of care today for thalassaemia patients in countries where this is accessible, feasible and affordable, and can be ethically recommended in patients with an available HLA‐matched donor 59 to drastically reduce disease burden and prevent long‐term morbidity and mortality in this population. Gene therapy constitutes an even more promising curative approach that overcomes the lack of an HLA‐matched donor.…”

Immune recovery after in vivo T‐cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta‐thalassemia children

“…Noteworthy, ATG-containing regimens reduced incidence of GVHD, and therefore, in our material, the rate of GVHD was relatively lower than in HSCT with non-ATG-conditioning regimens. [11][12][13] Of note, infections were the most common complication after transplantation, and occurred mostly within 6 months after transplantation.…”

Research progress of hereditary blood diseases

“…然而, 部分 研究者提出由于缺乏完全随机对照及半随机对照临 床实验, 无法准确评估异基因移植治疗不同亚型β地 贫患者的有效性及安全性 [7] . 更令人惊讶的是, 最新一 项长达30年的HSC移植后长期随访研究发现考虑到 排斥及严重移植物抗宿主病等不良事件的影响, HSC 移植患者长期随访后总生存率与传统治疗的患者并 无明显差异 [8] , 因而考虑移植时要综合评估移植获得 的收益及风险.…”