Wilfred Gilbert, Ong Tee Chuan, Sh Shahnaz Syed Abd Kadir, Wah Ho Kim, Carlo Edmund Syed, Jameela Sathar, Mui Tan Sen
Department of Haematology, Hospital Queen Elizabeth, Ministry of Health Malaysia Sabah.
Department of Haematology, Hospital Ampang, Ministry of Health Malaysia Selangor.
Blood Cell Ther. 2022 Apr 8;5(2):45-53. doi: 10.31547/bct-2021-018. eCollection 2022 May 25.
Hematopoietic stem cell transplantation (HSCT) provides curative therapy in almost 90% of patients with severe aplastic anemia (SAA). Older age, long duration of disease with consequent heavy exposure to transfusion, and active infection at the time of HSCT have a negative influence on the outcomes, causing graft failure (GF) and graft versus host disease (GVHD).
To describe the outcomes of all patients with SAA who received hematopoietic stem cell transplantation at a tertiary center in Malaysia.
We included a 20 y cohort of patients who underwent transplantation from January 1, 1999 to December 31, 2019. Data were obtained from electronic medical records. Demographics, clinical characteristics, and treatment outcomes were analyzed using descriptive statistics. Overall survival (OS) was analyzed using Kaplan-Meier curves. All analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 25.
Eighty patients were analyzed. The median age at diagnosis was 19 years, and 59% patients were male (n = 47). Malay ethnicity was the highest (52.5%), followed by Chinese (20.0%) and Native Sabah (15.0%). The median duration from diagnosis to transplantation was 13.5 weeks. A majority of patients received Cy-ATG conditioning (n = 51, 63.8%). Forty-one patients (51.2%) used peripheral blood as stem cell source, 36 patients (45.0%) used granulocyte colony stimulating factor (G-CSF) primed marrow graft and 3 patients (3.8%) used both. The mean nucleated mononuclear cell and CD34 cell doses were 4.7 ± 1.7 × 10/kg and 4.6 ± 1.9 × 10/kg, respectively. Median engraftment for WBCs and platelets was 14 and 15 days, respectively. There was no difference in WBC and platelet engraftment in patients who received peripheral blood stem cell transplantation or bone marrow transplant. At a median follow-up of 54 months, 49 patients (61.3%) achieved complete remission and 8 patients (10.0%) achieved partial remission. The estimated 5 y OS was 63% and higher among those who received HSCT within 3 months of diagnosis. Twenty-two patients (27.5%) died within 100 d of transplantation, and a majority of these died due to pre-engraftment death.
Our study found that patients who received early allogeneic transplantation for SAA had better outcomes. Pre-engraftment failure was the major cause of transplant-related mortality within 100 d. Further studies are required to identify the factors responsible for delaying transplantation to improve treatment outcomes.
造血干细胞移植（HSCT）可为近90%的重型再生障碍性贫血（SAA）患者提供治愈性治疗。年龄较大、病程较长导致大量输血以及HSCT时存在活动性感染会对治疗结果产生负面影响，导致移植物失败（GF）和移植物抗宿主病（GVHD）。
描述在马来西亚一家三级中心接受造血干细胞移植的所有SAA患者的治疗结果。
我们纳入了1999年1月1日至2019年12月31日期间接受移植的20年队列患者。数据来自电子病历。使用描述性统计分析人口统计学、临床特征和治疗结果。采用Kaplan-Meier曲线分析总生存期（OS）。所有分析均使用社会科学统计软件包（SPSS）25版进行。
分析了80例患者。诊断时的中位年龄为19岁，59%的患者为男性（n = 47）。马来族裔占比最高（52.5%），其次是华裔（20.0%）和沙巴原住民（15.0%）。从诊断到移植的中位时间为13.5周。大多数患者接受环磷酰胺联合抗胸腺细胞球蛋白预处理（n = 51，63.8%）。41例患者（51.2%）使用外周血作为干细胞来源，36例患者（45.0%）使用粒细胞集落刺激因子（G-CSF）动员的骨髓移植物，3例患者（3.8%）两者都使用。有核单个核细胞和CD34细胞的平均剂量分别为4.7±1.7×10/kg和4.6±1.9×10/kg。白细胞和血小板的中位植入时间分别为14天和15天。接受外周血干细胞移植或骨髓移植的患者在白细胞和血小板植入方面没有差异。中位随访54个月时，49例患者（61.3%）实现完全缓解，8例患者（10.0%）实现部分缓解。诊断后3个月内接受HSCT的患者估计5年OS为63%及更高。22例患者（27.5%）在移植后100天内死亡，其中大多数死于植入前死亡。
我们的研究发现，SAA患者早期接受异基因移植的治疗结果更好。植入前失败是移植后100天内与移植相关死亡的主要原因。需要进一步研究以确定导致移植延迟的因素，从而改善治疗结果。
