Spadea Manuela, Saglio Francesco, Tripodi Serena I, Menconi Mariacristina, Zecca Marco, Fagioli Franca
Pediatric Oncohematology, Stem Cell Transplantation and Cell Therapy Division, A.O.U. Città della Salute e della Scienza-Regina Margherita Children's Hospital, Turin, Italy.
Pediatric Hematology-Oncology, Fondazione Istituti di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
Transplant Direct. 2021 Oct 6;7(11):e774. doi: 10.1097/TXD.0000000000001226. eCollection 2021 Nov.
A timely and effective immune reconstitution after hematopoietic stem cell transplantation (HSCT) is of crucial importance to enhance graft-versus-leukemia reaction in hematological malignancies. Several factors can influence the yield of this process, and new mathematical models are needed to describe this complex phenomenon.
We retrospectively analyzed immune reconstitution in the early post-HSCT period in a multicenter cohort of 206 pediatric patients affected by acute lymphoblastic leukemia, acute myeloblastic leukemia, and myelodysplastic syndrome who received their first allo-HSCT. All patients were in complete morphological remission at transplantation and were followed-up at least 26 mo post-HSCT. Blood samples for analysis of lymphocyte subset numbers were collected at day 100 (±20 d).
The 2-y cumulative incidence of relapse was 22.2% (95% confidence interval [CI], 17.3-27). Using principal component analysis, we identified based on 16 input variables a new multivariate model that enables patients' description in a low-dimensional model, consisting of the first 2 principal components. We found that the numbers of CD3/CD4/CD8 lymphocyte subsets at day 100 post-HSCT and acute graft-versus-host disease had the greatest impact in preventing relapse. We ultimately derived a risk score defining high- or medium-low-risk groups with 2-y cumulative incidence of relapse: 35.3% (95% CI, 25.6-45) and 15.6% (95% CI, 10.1-20.7), respectively ( =0.001*).
Our model describes immune reconstitution and its main influencing factors in the early posttransplantation period, presenting as a reliable model for relapse risk prediction. If validated, this model could definitely serve as a predictive tool and could be used for clinical trials or for individualized patient counseling.
造血干细胞移植（HSCT）后及时有效的免疫重建对于增强血液系统恶性肿瘤中的移植物抗白血病反应至关重要。有几个因素会影响这一过程的结果，因此需要新的数学模型来描述这一复杂现象。
我们回顾性分析了206例接受首次异基因HSCT的急性淋巴细胞白血病、急性髓细胞白血病和骨髓增生异常综合征患儿多中心队列在HSCT后早期的免疫重建情况。所有患者在移植时均处于完全形态学缓解状态，并在HSCT后至少随访26个月。在第100天（±20天）采集血样分析淋巴细胞亚群数量。
2年复发累积发生率为22.2%（95%置信区间[CI]，17.3 - 27）。使用主成分分析，我们基于16个输入变量确定了一个新的多变量模型，该模型能够在由前两个主成分组成的低维模型中描述患者情况。我们发现HSCT后第100天的CD3/CD4/CD8淋巴细胞亚群数量和急性移植物抗宿主病对预防复发的影响最大。我们最终得出了一个风险评分，用于定义2年复发累积发生率的高风险或中低风险组：分别为35.3%（95%CI, 25.6 - 45）和15.6%（95%CI, 10.1 - 20.7）（P = 0.001）。
我们的模型描述了移植后早期的免疫重建及其主要影响因素，是一个可靠的复发风险预测模型。如果得到验证，该模型肯定可作为一种预测工具，用于临床试验或个体化患者咨询。
