Outcome of hematopoietic stem cell transplantation of children with very high risk acute lymphoblastic leukemia in first complete remission

Schechter T, Ishaqi KM, Rojas M, Irina Z, Doyle JJ, Gassas A. Outcome of hematopoietic stem cell transplantation of children with very high risk acute lymphoblastic leukemia in first complete remission.
Pediatr Transplantation 2010:14: 377–382. © 2009 John Wiley & Sons A/S. Abstract: Approximately 10% of children with ALL present at diagnosis with VHR for relapse if treated with chemotherapy alone. They may benefit from allogeneic HSCT in CR1. We have reviewed the outcome of this population in our institution. Forty‐three patients (median age: 8.9 yr) with VHR ALL in CR1 underwent HSCT from October 1994 to April 2006. VHR features included Philadelphia chromosome (n = 17), induction failure (n = 9), hypodiploidy (n = 6), MLL gene rearrangement (n = 5), and others (n = 6). All patients received TBI (1200 cGy) with either CY and/or etoposide. Stem cell source was unrelated (n = 24) and related (n = 19). Incidence of grade III‐IV acute GVHD and chronic extensive GVHD were 25% and 16%, respectively. Twelve patients relapsed (eight received related HSCT). Eleven patients died due to transplant‐related mortality (eight received unrelated HSCT). For a median follow up of 39 months (range 11–110), the event free survival and OS were 0.49 (95% CI: 0.31–0.67) and 0.53 (CI: 0.44–0.71), respectively. Outcomes of children with VHR ALL receiving HSCT in CR1 remain unsatisfactory. Relapse, mainly after related HSCT, and TRM, mainly after unrelated HSCT, continue to be major problems.     

Unrelated donor hematopoietic stem cell transplantation for pediatric de novo acute myeloid leukemia with intermediate‐ or high‐risk cytogenetics

The role of unrelated donor HSCT for children with de novo AML in CR1 is controversial. We performed this study to investigate the feasibility of unrelated donor HSCT who initially had intermediate‐ or high‐risk cytogenetics. We retrospectively reviewed medical records of patients with AML who received unrelated HSCT in CR1 at Samsung Medical Center between November 2001 and January 2012. Patients were allocated based on karyotype at diagnosis as follows: (a) low‐risk: inv(16), t(16;16), t(8;21), and t(15;17); (b) high‐risk: ‐5, 5q‐, ‐7, 3q abnormalities, t(8;16), t(6;9), t(6;11), t(6;21), t(10;11), complex karyotype (≥3 abnormalities), and acute megakaryocytic leukemia without t(1;22); and (c) IR: all the other karyotypes including normal. Patients in intermediate‐ or high‐risk group who were transplanted with either unrelated CB or matched unrelated BM/mobilized PB in their CR1 were included in this study. The projected OS and EFS rates were 74.9% and 71.1%, respectively, with a median follow‐up of 87.3 months after transplantation. The EFS was 70.1%, 80.7%, and 73.9% for CB, BM, and mobilized PB groups, respectively (P = 0.89), and 73.9% and 70.6% for IR and high‐risk groups (P = 0.76). The leading cause of death was relapse (n = 8), and only one patient died from non‐relapse cause. Unrelated donor HSCT seems a feasible approach for children with intermediate‐ or high‐risk AML in CR1. Relapse remains the leading cause of treatment failure among these patients.     

异基因造血干细胞移植治疗儿童慢性粒细胞性白血病的疗效分析

目的：研究异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation, allo-HSCT）治疗儿童慢性粒细胞性白血病（chronic myelogenous leukemia, CML）的治疗效果,寻找可能的影响因素,以期改善患者预后。方法：对接受allo-HSCT治疗的20例儿童CML患者,分别从年龄、性别、诊断至移植间隔时间、供受体HLA配型相合情况、移植时患儿疾病状态以及急慢性移植物抗宿主病（gost-v-host disease, GVHD）等多种因素进行疗效分析。结果：截止至随访日期,20例患者中,13例无病存活,7例死亡,其中4例死于急性重度GVHD,2例死于慢性GVHD及其并发症,1例死于移植后复发,3年总无病生存率为（64.6±1.1%）。单因素分析显示年龄是影响儿童CML治疗预后最重要的因素之一（P0.05）。多因素logistic回归分析也进一步证明仅年龄是影响预后的因素（P<0.01）。各种严重急慢性 GVHD是引起患者死亡最重要的原因。选择10位点全相合的供体进行移植治疗预后好。结论：allo-HSCT能有效治疗儿童CML,对于年龄≥10岁的CML患儿宜早期行allo-HSCT移植治疗,且尽可能选择10位点全相合的供体进行移植,积极防治GVHD,改善CML患儿移植治疗后的转归。     

Allogeneic stem cell transplantation for children with acute myeloid leukemia in second complete remission

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for patients with relapsed acute myeloid leukemia. In this retrospective, multicenter study, we analyzed the outcome of 63 children (median age, 7 y; range, 0.2 to 17) who received unmanipulated allo-HSCT in second complete remission. Either a matched family donor or an unrelated donor was used in 29 (46%) and 34 (54%) patients, respectively. The stem cell source was bone marrow in 53 children (84%), peripheral blood in 7 (11%), and cord blood in 3 patients (5%). Preparative regimen included total body irradiation in 25 patients (40%). The 5-year estimates of overall survival and leukemia-free survival were 53% [95% confidence interval (CI) 39-66] and 49% (95% CI 35-63), respectively, whereas the cumulative incidence of relapse and transplant-related mortality (TRM) were 26% (95% CI 16-41) and 25% (95% CI 15-40), respectively. In multivariate analysis, the use of a matched family donor predicted a better probability of LFS [relative risk (RR) 2.29, P=0.05]. Both chronic graft-versus-host disease occurrence and age at diagnosis greater than 11 years were associated with an increased TRM (RR 8.08, P=0.04 and RR 4.38, P=0.05, respectively). These results indicate that allo-HSCT is a procedure able to rescue a significant proportion of children with acute myeloid leukemia in second complete remission, especially if an human leukocyte antigen-compatible relative is employed as donor. Both leukemia recurrence and TRM contributed to treatment failure. Optimization of donor selection and of strategies for both prophylaxis and treatment of graft-versus-host disease may improve the results of unrelated donor allo-HSCT.     

异基因造血干细胞移植治疗儿童急性髓系白血病临床研究

目的评估应用异基因造血干细胞移植(allo-HSCT)治疗儿童急性髓系白血病(AML)的临床疗效及相关影响因素。方法回顾分析2002年1月至2017年11月49例确诊中、高危及复发AML行allo-HSCT患儿的临床资料,分析危险度分级、HLA分型、移植前状态、移植方式、干细胞来源及急慢性移植物抗宿主病(GVHD)等对allo-HSCT治疗效果的影响。结果 49例患儿中男35例、女14例,中位年龄9岁。三年总体存活率(OS)为(59.2±7.3)%,无白血病存活率(LFS)为(50.9±7.4)%。其中第1次缓解状态移植、非血缘移植、外周血干细胞移植、中危组移植的三年LFS分别为69.8%、69. 2%、73. 7%、65. 8%。19例死亡,分别为复发13例、严重感染5例、多器官衰竭1例。COX回归模型结果显示,急性GVHD是影响移植OS的独立危险因素(RR=3. 16,95%CI:1. 23～8. 09,P=0. 017),移植前状态为部分缓解及未缓解是影响移植LFS的独立危险因素(RR=4.76,95%CI:1.52～14.94,P=0.008;RR=5.28,95%CI:1.68～16.58,P=0.004)。结论移植前状态及急性GVHD是影响Allo-HSCT治疗儿童AML疗效的关键因素;白血病复发及感染是导致死亡的主要原因。     

The treatment of children suffering from chronic myelogenous leukemia: A comparison of the result of treatment with imatinib mesylate and allogeneic hematopoietic stem cell transplantation

HSCT is the only proven treatment option for CML, a rare disease in children. Recently, there are promising reports on the advantageous effect of imatinib mesylate for pediatric patients with CML. We conducted a retrospective study on 33 pediatric patients suffering from CML. Fourteen underwent HSCT and the rest were treated with imatinib. With a median follow‐up of 24 months, the two‐yr OS in the HSCT group and the imatinib group was 84% and 87%, respectively (p = 0.714). The probabilities of two‐yr DFS were 59% in the HSCT group and 82% in the imatinib group, either (p = 0.880). Relapse occurred in 5 (35.7%) patients of the HSCT group, and 8 (42.1%) patients showed relapse in the imatinib group. Among nine patients who died, five were in the HSCT group and the rest were in the imatinib group. The probability of relapse in the patients of the imatinib group followed up for several consecutive years may be higher than observed in the HSCT group, so we cannot easily conclude which way is more reliable.     

异基因造血干细胞移植治疗儿童再生障碍性贫血临床分析

目的探讨异基因造血干细胞移植在儿童再生障碍性贫血治疗中的作用。方法10例再障患儿中,5例行HLA相合同胞供者异基因外周造血干细胞移植,3例行无关供者异基因外周造血干细胞移植,1例行无关供者骨髓移植,1例行脐血移植。结果1例接受脐血移植者未植活,其余9例均植入。中位植入时间14d（8～24d）,中性粒细胞〉0.5×10^9/L中位时间12d（8～19d）,血小板〉20×10^9/L中位时间17d（9～40d）。2例发生排斥,1例接受了第二次移植,1例移植后3个月血象开始自行恢复。结论如有HLA相合的同胞供者,异基因造血干细胞移植可作为儿童再障的一线治疗;临床重症感染无法控制的患儿,并非移植绝对反指征,相反可通过移植后的造血重建控制感染。     

Outcome of autologous hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory Hodgkin's lymphoma

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty‐nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara‐C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow‐up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non‐relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.     

Correction of celiac disease after allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia

Allogeneic hematopoietic stem cell transplantation has been shown to correct or improve a variety of autoimmune disorders. This has not been reported for celiac disease, but transmission to a hematopoietic stem cell transplantation recipient from a donor with celiac disease has been reported. We report a 12-year-old girl with celiac disease who was diagnosed with acute leukemia and received an allogeneic hematopoietic stem cell transplant. Her celiac disease resolved after the hematopoietic stem cell transplant.     

Hematopoietic stem cell transplantation for children with primary immunodeficiency diseases: Single center experience in Jordan

HSCT can be curative for many PID. Little is known about the outcome of HSCT for patients with PID in the developing countries. We retrospectively reviewed all children with PID who received HSCT at KHCC in Jordan between August 2003 and October 2011. Twenty‐eight patients were identified. The median age was 16 months (3 months–17 yr). Patients' diagnoses were SCID (n = 16), CHS (n = 3), HLH (n = 3), WAS (n = 2), Griscelli syndrome (n = 1), ALPS (n = 1), Omenn's syndrome (n = 1), and DiGeorge syndrome (n = 1). Seventeen patients received HLA‐matched related HSCT, eight received maternal un‐manipulated haploidentical HSCT, and three received unrelated cord blood transplantation. Nine patients (32%) developed BCGosis secondary to reactivation of pretransplant vaccination. Three died while still receiving anti‐tuberculosis drugs, one still on treatment, and all others have recovered. Six patients had graft failure; four of them received no conditioning regimens. At a median follow up of 32 months (range 1‐67), 21 patients are alive, with overall survival of 72%. We conclude that HSCT for PID patients can be performed with a good outcome in developing countries; however, delayed diagnosis or referral and BCG reactivation are unique challenges.     

Similar outcomes of allogeneic hematopoietic cell transplantation from unrelated donor and umbilical cord blood vs. sibling donor for pediatric acute myeloid leukemia: Multicenter experience in China

In a multicenter study, we have conducted a retrospective study on 73 pediatric AML patients who were primary refractory or in greater than CR1 and investigated MSD (or MMSD) (n = 20), URD (n = 23), and UCB (n = 30) HCT between January 1998 and October 2009. The median day to neutrophil engraftment was similar in all groups. The median day to platelet engraftment was longer in the UCB group. The number of HLA mismatch was higher in the UCB group (p = 0.034); however, the cumulative incidence of grade III–IV aGVHD was not different among all groups (p = 0.125); furthermore, cGVHD was lower in the UCB group (p = 0.078). The risk of relapse did not differ among all groups (RR = 1.28, p = 0.125), but the patients of MSD (or MMSD) grafts had a trend of higher risk recurrence. Sixty‐two patients survived with a median follow‐up of 58.2 months. Five‐yr LFS was 73.1%, 59.8%, and 59.6% for URD, UCB, and MSD (or MMDS), respectively (p = 0.426). Five‐yr LFS in CR1 was 68.9%, with a significantly better result compared to 41.7% in CR2 (p = 0.025). Our comparisons suggest that pediatric AML patients receiving UCB had a higher early TRM, a lower cGVHD rate, and a similar long‐term survival. The outcome of URD and UCB is comparable to that of a suitable sibling for pediatric AML.     

无关供体造血干细胞移植治疗46例儿童难治性白血病疗效分析

目的 评估无关供体造血干细胞移植(UDT)治疗儿童难治性白血病的疗效.方法 回顾性分析连续在我院接受UDT的46例白血病患儿的临床资料.急性淋巴细胞性白血病(ALL)患儿接受全身放疗为主的预处理、急性髓细胞性白血病(AMI)和慢性粒细胞性白血病(CML)患儿采用白消安清髓.结果 中位年龄8.0(2～17)岁,3年总存活率(OS)63.0%,23.9%患儿死于移植相关并发症,13.0%患儿死于白血病复发.移植过程中33.3%出现Ⅲ～Ⅳ度急性移植物抗宿主病(aGVHD),55.6%发生慢性移植物抗宿主病(GVHD)(13.9%为慢性广泛性GVHD).大于10岁、小于10岁患儿的OS差异有统计学意义(45.0%vs. 76.9%,P=0.015);ALL患儿3年OS明显差于CML和AML(38.4%、66.7%vs. 80.0%,P=0.034);高危白血病疗效明显差于低危患儿(45.8% vs.81.8%,P=0.012);人类白细胞抗原(HLA)高分辨6/6全相合、1/6不合较2/6位点不合患儿的OS显著增高(75.0%,75.0% vs.16.7%,P=0.007);移植中出现Ⅲ～Ⅳ度与0～Ⅱ度aGVHD患儿相比OS差异无统计学意义(66.0% vs.66.7%,P=0.494).结论 UDT治疗我国儿童难治性白血病疗效令人满意.小于10岁、HLA相合度高是UDT的有利因素,髓系、低危白血病疗效优于其他白血病.     

Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT.     

儿童异基因造血干细胞移植后急性肾损伤临床分析

目的分析儿童异基因造血干细胞移植(allo-HSCT)后急性肾损伤(AKI)的临床特征及危险因素。方法回顾性分析2016年8月至2020年3月于武汉儿童医院血液肿瘤科接受allo-HSCT患儿的临床资料,对比移植预处理开始前及移植后100天血肌酐(Cr)、肌酐清除率(Ccr),以及移植后1年的生存情况;采用logistic回归分析影响AKI发生的危险因素。结果共147例allo-HSCT患儿纳入研究,其中男85例、女62例,接受移植时中位年龄5.5岁(0.7个月～16岁)。其中101例(68.7%)患儿发生AKI,中位时间为移植后24.0(-5.0～91.0)d。二元logistic回归分析显示,移植后急性移植物抗宿主病(aGVHD)、肝窦间隙阻塞综合征(SOS)是AKI发生的独立危险因素(P<0.05)。按pRIFLE诊断标准将发生AKI的101例患儿分为风险期组54例、肾损伤期组31例以及肾衰竭期组16例。不同分期之间患儿Cr以及Ccr差异均有统计学意义(P<0.05),肾衰竭期组Cr较高,Ccr较低。allo-HSCT后随访1年,18例患儿死亡,其中AKI患儿死亡16...