Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology‐oncology

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male‐to‐female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo‐HSCT). In total, 29 patients received HSCT from either a matched‐related donor or a mismatched‐related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5‐year overall survival (OS) was 73.1% (95% CI: 62.7‐83.5) and the 5‐year event‐free survival (EFS) was 66.1% (95% CI: 54.5‐77.7). There was no statistical difference in 5‐year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5‐year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5‐year relapse rate was 16.1% (95% CI: 7.3‐24.9) and the 5‐year non‐relapse mortality (NRM) was 13.3% (95% CI: 5.1‐21.5). There was no statistical difference in the 5‐year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5‐year NRM between donor types or stem cell sources (P = .461 and P = .470).     

Retrospective analysis of children with high‐risk acute myeloid leukemia who underwent allogeneic hematopoietic stem cell transplantation following complete remission with initial induction chemotherapy in the AML‐05 clinical trial

In the AML‐05 clinical trial conducted by the Japanese Pediatric Leukemia/Lymphoma Group from 2006 to 2010, children with high‐risk acute myeloid leukemia (HR AML) received allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1). The aim of this study was to investigate the impact of allo‐HSCT on the outcome of HR AML. Patients with either monosomy 7, 5q?, t(16;21), Ph1, FLT3‐ITD, or induction failure after the first course of chemotherapy were eligible for transplant. Of 53 children with HR AML, 51 received allo‐HSCT—45 in CR1, five in CR2, and one with non‐CR. t(8;21), t(9;11), and t(16;21) abnormalities were identified in eight, five, and four patients, respectively. The stem cell sources varied—bone marrow in 30 patients, peripheral blood in three, and cord blood in 18. The median follow‐up was 62 months. The overall survival (OS) rates at 3 years were 73% and 25% for patients who received transplant at CR1 and ≥CR2, respectively. Multivariable analysis showed that patients with chronic graft‐versus‐host disease (cGVHD) had better OS. This study supports that allo‐HSCT is a suitable treatment for HR AML in CR1. The favorable outcome associated with cGVHD indicates that a graft‐versus‐leukemia effect might be occurring.     

Matched related donor hematopoietic stem cell transplantation results in a long‐term follow‐up of a pediatric acquired severe aplastic anemia subset: A stem cell source perspective

HSCT has substantially improved pediatric acquired SAA patients' outcomes. Retrospectively, we attempted to assess the outcome of MRD HSCT in 65 pediatric patients referred to a single center from 1992 to 2012. We were particularly interested to find out whether source of SC (PB, n = 40 and BM, n = 25) significantly impacts EFS and GVHD incidence. With a median follow‐up of 45 months, total EFS was 87.7%; EFS for PB and BM groups was 87.5% and 88%, respectively. Acute GVHD (grades 3–4) occurred in 13 patients (PB, n = 10 [25%] and BM, n = 3 [12%]), acute GVHD (grades 2–4) occurred in 24 (PB, n = 16 [40%] and BM, n = 8 [32%]). Extensive chronic GVHD occurred in five patients (PB, n = 3 [7.5%] and BM, n = 2 [8%]). Cox regression revealed that elapsed time of <10 months between diagnosis and HSCT is associated with improved survival (hazard ratio, 95% CI = 1.204, 1.010–1.434, p = 0.038). SC source did not significantly affect EFS, incidence of acute GVHD (grades 3–4), or extensive chronic GVHD (p = 0.938, 0.121, and 0.487, respectively). Based on our findings, pediatric acquired SAA patients are benefitted most if MRD‐HSCT is carried out early in disease process and SC source does not affect outcome of MRD‐HSCT in these patients.     

Hematopoietic stem cell transplantation in pediatric patients with acute myeloid leukemia without favorable cytogenetics

Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of the 65 patients died: three of TRM and 12 of disease‐related mortality. The 5‐year OS and EFS were 78.0% and 72.0%, respectively, and the 5‐year cumulative relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not influenced by cytogenetic group (intermediated vs. poor), donor type (related vs. unrelated), transplant type (myeloablative vs. reduced‐intensity conditioning), or number of pretransplant chemotherapy cycles (≤3 vs. >3 cycles). The low TRM rate and encouraging outcomes suggest that HSCT may be a feasible treatment for pediatric patients with AML without favorable cytogenetics.     

Transplant‐related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25‐year retrospective review

Background

Over the last 25 years, donor source, conditioning, graft‐versus‐host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high‐risk patients in first and subsequent remission. There is a large burden of infectious and pre‐HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.

Procedure

A retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8‐year periods (Period 1: 1/1/1984–31/8/1992, Period 2: 1/9/1992–30/4/2001, Period 3: 1/5/2001–31/12/2009).

Results

Despite a significant increase in unrelated donor HSCT, event‐free and OS over 25 years improved significantly. (EFS 31.6–64.8%, P = 0.0027; OS 41.8–78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.

Conclusion

EFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post‐HSCT are unchanged, and remain the focus for improvement. Pediatr Blood Cancer 2013;160:1520–1527. © 2013 Wiley Periodicals, Inc.     

Low‐dose total‐body irradiation and alemtuzumab‐based reduced‐intensity conditioning regimen results in durable engraftment and correction of clinical disease among children with chronic granulomatous disease

HSCT with MAC is associated with durable donor engraftment for patients with CGD; however, MAC is limited by high rates of RRT. We used a novel RIC regimen with LD‐TBI (200 cGy × two doses), fludarabine (30 mg/m² × three doses), and proximal alemtuzumab (0.5 mg/kg/dose × one dose) and unrelated donor grafts for consecutive patients with high‐risk CGD who were not candidates for MAC at our institution. Among four children with CGD transplanted at our institution, three PBSC recipients are alive with sustained donor engraftment (median follow‐up: two yr) and resolution of pre‐HSCT active infections while one patient with bone marrow graft is alive after graft failure and autologous recovery. RIC may be a curative option for children with high‐risk CGD.     

Outcome of allogeneic hematopoietic stem cell transplantation for children with acute myelogenous leukemia in second complete remission: Single center experience

Abstract: We reviewed 26 consecutive patients with AML who were transplanted in second CR2 between 1994 and 2005. The most common conditioning regimen was CY and TBI. Median age at transplant was 8.9 yr (range 2.2–18.2). Nine patients received related donor, 16 patients received unrelated donors, and one patient received unrelated cord stem cells. Acute grade III–IV and chronic extensive GVHD occurred in eight (30%) and nine (35%) patients, respectively. Six patients (23%) relapsed, four of them died. Six patients (23%) died from TRM. Estimate of three‐yr EFS was 0.53 (95% CI; 0.34–0.72). Including the two relapsed patients who were salvaged by DLI and second transplantation, three‐yr OS was 0.61 (95% CI; 0.41–0.78) with a median follow‐up of three and a half yr (range 1.5–11.2 yr). When entering remission, children with relapsed AML have a reasonable survival with HSCT, but relapse and TRM remain a concern.     

Unrelated donor hematopoietic stem cell transplantation for infantile enteropathy due to IL‐10/IL‐10 receptor defect

Recent advances in genetic diagnosis have identified mutations in gene encoding interleukin‐10 (IL‐10) and IL‐10 receptor (IL‐10R) proteins as a cause for early‐onset enterocolitis leading to hyperinflammatory immune response. Allogeneic HSCT offers a potential cure; however, it was only performed in a few infants and mainly from family‐related donors. We report a case of a girl who presented very early in life with severe infantile enterocolitis. Gene sequencing confirmed IL‐10R defect. Her older sister died at 13 months of age from severe undiagnosed enterocolitis. There was no family donor. An unrelated search identified a potential 10/10 high‐resolution HLA‐matched donor. There was some delay in donor activation because IL‐10R defect was not on the standard list of indications for unrelated HSCT. Our patient received the unrelated HSCT at seven months of age, and she is currently nine months after transplant and doing very well. Because HSCT is the curative option of choice for this disorder, we encourage adding IL‐10 and IL‐10R protein defects to the list of HSCT indications for unrelated donor procurement.     

Favorable outcomes after allogeneic hematopoietic stem cell transplantation in children with high-risk or advanced acute myeloid leukemia

The role of allogeneic hematopoietic stem cell transplantation (HSCT), including transplantation from an alternative donor (AD), has not been clearly defined for children with high-risk or advanced acute myeloid leukemia (AML). We retrospectively reviewed outcomes in 29 children (median age at HSCT, 6.7 y; range, 1.0-16.2 y) with high-risk or advanced AML who underwent allogeneic HSCT at the Asan Medical Center between 1998 and 2008. Donors included a matched sibling donor (MSD) for 7 patients (24%), an unrelated volunteer for 21 patients (72%), and a haploidentical mother for 1 patient (3%). The 3-year estimates of overall survival and event-free survival (EFS) were 77% [95% confidence interval (CI), 65%-99%] and 70% (95% CI, 57%-93%), respectively, whereas the cumulative incidences of relapse and transplant-related mortality were 33% (95% CI, 5%-58%) and 7% (95% CI, 0%-44%), respectively. The 3-year EFS rates did not differ between MSD and AD HSCT. Univariate analysis showed that age ≥ 10 years at diagnosis was the only factor associated with poorer EFS. Development of acute graft-versus-host disease predicted a significantly lower incidence of relapse. These findings may provide further evidence that allogeneic HSCT is a curative therapy for children with high-risk or advanced AML, and suggest the efficacy of AD transplantation.     

Transplant‐related mortality and survival in children with malignancies treated with allogeneic hematopoietic stem cell transplantation. A multicenter analysis

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant‐related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high‐risk group (P = .006). High‐risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.     

The challenge of long‐term follow‐up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource‐limited countries: A single‐center report from Brazil

With the number of long‐term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18 years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow‐up was 5.9 years (2.0‐29.0); median age at follow‐up was 17.5 years (2.98‐39.0). The 5‐year cumulative incidence of relapse was 27.5% (95% CI 18.6%‐36.4%). Two‐year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%‐29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI‐based regimen developed more late effects (P = .013) and more endocrinological complications (P = .024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow‐up.     

BCH-AML05方案治疗儿童急性髓细胞性白血病的疗效评估

目的 总结BCH-AML05方案分层治疗儿童急性髓细胞性白血病（AML）的临床疗效,探讨如何进一步提高儿童AML无事件生存（EFS）率。方法 回顾性分析首都医科大学附属北京儿童医院2005年1月至2014年6月收治的初治AML患儿的临床特点及治疗疗效。采用Kaplan-Meier方法评估患儿的总体生存（OS）率及EFS率。结果 185例初治AML（除M3外）患儿纳入分析,均接受了BCH-AML05方案治疗,其中标危47例、中危90例、高危48例。中位随访时间24（0.5~129）个月。①第一疗程达完全缓解(CR)者106例(57.3%),第二疗程达CR者45例（24.3%）,总CR率为81.6%。②8年OS率和EFS率分别为(66.2±4.2)%和(54.1±5.5)%,标危组分别为(65.7±10.4)%和(57.2±8.5)%,中危组分别为(70.3±5.2)%和(60.2±7.4)%,高危组分别为(51.6±10.1)%和(31.3±14.5)%。③34例（18.4%）接受了造血干细胞移植,8年OS率及EFS率分别为(73.5±9.5)%和(67.7±9.9)%。④复发36例(19.5%),中位复发时间12(3.5~ 53)月。死亡52例（28.1%）,其中化疗相关死亡20例（10.8%）;诱导失败死亡11例（5.9%）,复发相关死亡18例（9.7%）;早期死亡率为5.4%。⑤154例行Flt3基因突变检测,Flt3-ITD阳性16例（10.4%）,其中6例（37.5%）诱导化疗后达CR,11例（68.8%）死亡。结论 BCH-AML05方案为儿童AML有效的化疗方案,精准的危险度分层更能提高AML患儿的长期生存率。高危患儿应尽早接受造血干细胞移植。     

Impact of post‐transplant minimal residual disease on the clinical outcome of pediatric acute leukemia

This retrospective study examined the clinical significance of FCM‐MRD in 36 patients with ALL and 29 patients with AML after their first allogeneic HSCT. Hematological (FCM‐MRD ≥5.0%) and molecular relapse (FCM‐MRD <5.0%) were first detected in 10 and two patients with ALL and in seven and eight patients with AML, respectively. Eight of 10 patients with molecular relapse eventually progressed to hematological relapse, although most were treated with immunological intervention by aggressive discontinuation of immunosuppressive therapy or donor lymphocyte infusion. Among these 12 patients, four of seven patients that obtained MRD^neg CR following post‐transplant chemotherapy remain alive and disease‐free after their second HSCT; however, all five patients who underwent a second HSCT in non‐CR died of disease or treatment‐related complications. As the FCM‐MRD monitoring system used in the current study was probably not sensitive enough to detect MRD, which could be elucidated by immunological intervention, more sensitive diagnostic tools are mandatory for post‐transplant MRD monitoring. Additional studies are required to address the impact of presecond transplant MRD on the clinical outcome of second HSCT.     

Unrelated and related donor transplantation for beta‐thalassemia major: A single‐center experience from India

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with β‐thalassemia major. A matched sibling or a related donor is usually found in only 25%‐30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT‐based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow‐up of 25 (1‐92) months and 22.5 (1‐50) months, respectively (P=.757). The thalassemia‐free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow‐up of 24 (1‐92) and 16.5 (1‐50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft‐versus‐host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non‐infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan‐based regimen using PBSC grafts.     

Control of graft‐versus‐host disease with rabbit anti‐thymocyte globulin,rituximab, and bortezomib in TCRαβ/CD19‐depleted graft transplantation for leukemia in children: a single‐center retrospective analysis of two GVHD‐prophylaxis regimens

Both acute GVHD and chronic GVHD remain the leading cause of morbidity and death after allogeneic HSCT. We conducted a retrospective analysis comparing two GVHD‐prophylaxis regimens: 35 patients received “Regimen 1” (horse ATG, tacrolimus, and methotrexate) and 46 “Regimen 2” (rabbit ATG, rituximab, and peritransplant bortezomib). All 81 patients with a median age of 9 (0.6‐23) years with ALL (n = 31) or AML (n = 50) in complete remission received TCRαβ/CD19‐depleted transplants between May 2012 and October 2016, from 40 HLA‐matched unrelated and 41 haploidentical donors. After a median follow‐up of 3.9 years, the CI of acute GVHD II‐IV was 15% (95% CI: 7‐30) in the “Regimen 2” group and 34% (95% CI: ?54) in the “Regimen 1” group, P = .05. “Regimen 2” was also more effective in the prevention of chronic GVHD; the CI at 1 year after HSCT was 7% (95% CI: 2‐19) vs 31% (95% CI: 19‐51), P = .005. The CI of relapse at 3 years adjusted for the GVHD‐prophylaxis regimen groups 31% (95% CI: 19‐51) for the “Regimen 1” vs 21% (95% CI: 11‐37) for the “Regimen 2”, P = .3. The retrospective observation suggests that the use of the rATG, rituximab, and bortezomib was associated with significantly lower rate of GVHD without the loss of anti‐leukemic activity.     

Comparison of outcomes after HLA‐matched unrelated and αβ T‐cell‐depleted haploidentical hematopoietic stem cell transplantation for children with high‐risk acute leukemia

T‐cell‐depleted HAPLO HSCT is an option to treat children with high‐risk acute leukemia lacking an HLA‐identical donor. We reviewed the outcome of children with acute leukemia after HAPLO (n = 21) and HLA‐MUD (n = 32) transplantation. The proportion of patients with ≥CR2 was significantly higher in HAPLO transplantation than MUD transplantation. Patients with MUD transplantation were significantly higher ABO incompatible than patients with HAPLO transplantation. There was no difference between the 2 groups in terms of engraftment, aGvHD and cGvHD, VOD, hemorrhagic cystitis, infections, and relapse. The 5‐year OS of MUD transplantation and HAPLO transplantation groups was found 65.8% and 71.1%, respectively (log‐rank 0.51). The 5‐year RFS was 80.7% for MUD transplantation group and 86.9% for HAPLO transplantation group (log‐rank 0.48). There was no statistically significant difference between 2 groups according to TRM (25% MUD transplantation vs 16.3% HAPLO transplantation, log‐rank 0.48). These data suggest that survival for patients with high‐risk acute leukemia after HAPLO transplantation with ex vivo ɑβ⁺ T‐cell depletion is comparable with MUD transplantation.     

Increased p53 protein expression as a potential predictor of early relapse after hematopoietic stem cell transplantation in children with acute myelogenous leukemia

Dysregulation of genes involved in the cell cycle such as TP53, P21, P16, and PTEN plays a key role in oncogenesis. We have earlier reported increased expression of the TP53 encoded protein p53, in bone marrow samples from pediatric patients with more aggressive, rare chronic myeloid malignancies. The aim of this study was to investigate protein expression of p53, p21, p16, and PTEN before and after HSCT in pediatric patients with AML and evaluate whether any potential alterations could predict relapse after HSCT. Paraffin‐embedded bone marrow samples from 34 pediatric patients with AML were collected retrospectively from time of diagnosis as well as pre‐ and post‐HSCT. IHC was performed on tissue microarrays with antibodies against p53, p21, p16, and PTEN. Study material was analyzed by independent t‐tests and nonlinear regression. t‐Tests showed a statistical significant difference in p53 (p = 0.010) with overexpression in the group of patients who relapsed compared to the relapse‐free patients at >3–6 months post‐HSCT. Analysis of p53 protein expression by IHC may be a potential predictor for relapse after HSCT in children with AML.     

Hematopoietic stem cell transplantation without in vivo T‐cell depletion for pediatric aplastic anemia: A single‐center experience

For young patients, HLA‐MRD HSCT is the first‐line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA‐MUD. More and more transplantation centers have used Haplo‐D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo‐HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty‐two had grade I‐IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo‐HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3‐ and 5‐year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo‐HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.     

伴t(8;21)/AML1-ETO阳性的儿童急性髓系白血病的临床特点及预后研究

目的分析伴t(8;21)/AML1-ETO阳性的儿童急性髓系白血病（AML）的临床特点、生物学特征及预后。方法对伴t(8;21)/AML1-ETO阳性的55例AML患儿的临床资料进行回顾性分析,采用Kaplan-Meier 曲线评估患儿的无事件生存（EFS）率、无病生存(DFS)率和总生存(OS)率,COX回归模型评估预后因素。结果①55例伴t(8;21)/AML1-ETO阳性患儿中,4例放弃治疗,4例化疗1疗程后失访,47例患儿进行了双诱导方案化疗,1疗程、2疗程完全缓解率分别为71%和94%,复发10例（21%）,47例患儿的5年EFS率、DFS率、OS率分别为（56.1±7.9）%、（59.8±8.1）%、（72.0±8.1）%。②多因素分析显示年龄是影响患儿预后的独立危险因素,年龄越大出现事故或死亡的风险性越大（P<0.05）。③缓解后继续巩固强化规范化疗的患儿（n=27）5年OS率明显高于不规范化疗的患儿（n=13）［（47.5±17.1）% vs （38.9±17.3）%,P<0.01］。结论伴t (8;21)/AML1-ETO阳性儿童AML是一类具有高度异质性的疾病,其治疗完全缓解率高,远期疗效好,年龄是决定远期疗效的重要因素之一,完全缓解后进行巩固强化规范化疗疗效较好。     

Low‐dose azacitidine maintenance therapy after allogeneic stem cell transplantation for high‐risk pediatric acute myeloid leukemia

The dismal prognosis of pediatric acute myeloid leukemia (AML) relapsing after hematopoietic stem cell transplantation (HSCT) requires exploration of novel strategies to prevent relapse. Azacitidine (AZA) maintenance therapy could potentially reduce the recurrence rate post HSCT. Here, we presents the cases of three children with high‐risk AML post HSCT who were treated with low‐dose AZA maintenance therapy, demonstrating the feasibility of this therapy. Currently, all three are in complete remission for 13–41 months despite their high‐risk characteristics. Our encouraging data warrant larger prospective studies to assess the efficacy and safety of low‐dose AZA maintenance therapy post HSCT for pediatric patients with high‐risk AML.