Bone Marrow Transplantation | 2021
Outcomes of severe aplastic anemia patients with infection proceeding with allogeneic hematopoietic stem cell transplantation, versus patients without infection
Abstract
TO THE EDITOR How should we select specific treatments for severe aplastic anemia (SAA) patients in the presence of active infection is still the challenge in the management of these patients. Infection is an adverse factor for outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1]. However, it is sometimes necessary to proceed with HSCT in the presence of active infection because HSCT offers the best chance of early neutrophil recovery, and delaying it can risk progression of the infection [2]. HSCT in SAA patients with active infections is therefore called “salvage therapy” or “salvage transplant”. Xu et al. reported 65 SAA patients with infection who received allo-HSCT and had encouraging results [3]. We do not know, however, the outcomes of SAA patients with infections who proceed with allo-HSCT, compared with those of SAA patients without infection who proceed with said treatment. In this multicenter study, we retrospectively summarized 133 SAA patients with active infections who received allo-HSCT as “first-line salvage therapy” between July 2005 and August 2019 and compared them with 300 SAA patients without infection who underwent allo-HSCT during the same time period. All patients provided written informed consent for the protocol. This study was approved by the Ethics Committees of our centers. Infection was assessed per The Common Terminology Criteria for Adverse Events Version 4.0 [4]. Details of the treatment of infection, conditioning regimen, graft collection and infusion, GVHD prophylaxis and treatment strategy, supportive care and post-transplantation surveillance, and other supportive care are consistent with our previous experience [3, 5]. Statistical analyses were conducted on the basis of data available from the date of treatment to the date of final patient follow-up on June 30, 2020. We compared patient characteristics using the chi-square test and the non-parametric test for continuous variables. Cumulative incidences of graft-versus-host disease (GVHD) were estimated using the competing-risk model, with death as the competing event. We estimated the probabilities of overall survival (OS) and failure-free survival (FFS), from the time of treatment using the Kaplan–Meier method and compared them between different patient groups using the log-rank test. Statistical analyses were performed with SPSS software version 16.0 (IBM Corp. Armonk, NY, USA). All P-values were 2 sided, and results were considered statistically significant when P < 0.05. Characteristics of patients and donors are listed in Table 1. The rate of very SAA (vSAA) was higher in the infection group than in the non-infection group (P < 0.001). Median interval between diagnosis and treatment was longer in the non-infection group than in the infection group (P < 0.001). As shown in Table 1, there were no differences in early mortality, primary graft failure, secondary graft failure or platelet graft failure, median time to neutrophil engraftment or platelet engraftment. Cumulative incidences were as follows in the infection group versus noninfection group, respectively: grade II–IV aGVHD on day +100, 23.66% ± 3.71% versus 17.01% ± 2.19% (P= 0.088); grade III–IV aGVHD on day +100, 6.92% ± 2.23% versus 5.78% ± 1.36% (P= 0.625); total cGVHD, 38.81% ± 4.65% versus 20.90% ± 2.49% (P= 0.0002); and moderate-to-severe cGVHD, 11.77% ± 3.07% versus 6.91% ± 1.57% (P= 0.132). In the non-infection group, 152 patients (50.67%) experienced infections during the transplantation period. Transplantation-related mortality (TRM) rates were 18.70% ± 3.44% and 21.84% ± 3.73% in the infection and noninfection groups, respectively (P= 0.850). Causes of TRM are listed in Table 1. TRM due to infection was higher in the infection group than in the non-infection group (14.29% vs. 5.33%; P= 0.002). Median follow-up time among living patients was 58 (range, 10–134) and 49 (range, 10–214) months in the infection and noninfection groups, respectively. No patient relapse occurred during the follow-up period in the infection group, and two patients in the non-infection group experienced relapse within 1-year posttransplantation. Probability of 5-year OS was 78.9% ± 3.6% in the infection group and 81.7% ± 2.3% in the non-infection group, but the difference was not statistically significant (P= 0.485). Probability of 5-year FFS was 76.5% ± 3.9% in the infection group and 80.8% ± 2.3% in the non-infection group, again without a statistically significant difference (P= 0.483). Probability of 5-year OS of grade 1–2 and 3–4 infections was 79.8% ± 5.7% and 78.3% ± 4.5%, respectively (P= 0.670). There was no statistically significant difference between the grade 1–2 infection and non-infection groups (P= 0.899), nor between the grade 3–4 infection and non-infection groups (P= 0.389). Probability of 5-year FFS for grade 1–2 and grade 3–4 infections was 73.6% ± 6.9% and 78.3% ± 4.5%, respectively (P= 0.911); there was no statistically significant difference between the grade 1–2 infection and non-infection groups (P= 0.600), nor between the grade 3–4 infection and noninfection groups (P= 0.575). For patients aged ≤ 20 years, the estimated OS at 5 years was 86.3% ± 5.2% in the infection group and 84.5% ± 3.6% in the non-infection group (P= 0.820); the estimated FFS at 5 years was 86.3% ± 5.2% in the infection group and 83.2% ± 3.7% in the non-infection group (P= 0.690). For patients aged 21–39 years, the estimated OS at 5 years was 75.2% ± 5.4% in the infection group and 79.5% ± 3.4% in the non-