ABSTRACT
Objective@#To investigate the efficacy of alternative donor (AD) in the treatment of aplastic anemia (AA) in children.@*Methods@#The clinical data of AA children who received AD HSCT in our center from Apr. 2010 to Dec. 2016 were retrospectively analyzed. The overall survival (OS) rate, implant success rate, incidence of acute and chronic graft-versus-host disease (GVHD) were statistically analyzed.@*Results@#A total of 109 children with acquired AA, including 64 severe AA (SAA) , 32 very severe AA (VSAA) and 13 transfusion dependent non-severe AA (NSAA) , were recruited in this retrospective AD HSCT study, the median age was 6 (0.8-18) years old. Of them, 44 patients with 10/10 matched unrelated donor (MUD) , 44 patients with mismatched unrelated donor (MMUD) and 21 patients with mismatched related donor (MMRD) . All patients did not receive ATG before HSCT and the active infection was excluded. Except 3 patients suffered from a second graft failure (2 of them rescued by second HSCT) , 106/109 (97.2%) were engrafted with neutrophil and platelet recovery occurring at a median of 13 days (range, 9-19) and 16 days (range, 10-81) post-transplant. Until day 100 post transplantation, the incidence was 74.3% (81/109) for acute GVHD (aGVHD) and 39.4% (43/109) for grade Ⅱ-Ⅳ aGVHD, 30.7% (31/101) and 9.9% (10/101) for overall chronic GVHD (cGVHD) and moderate cGVHD, respectively, and nobody developed an extend cGVHD. After median follow up of 39 (0.7-103) months for all patients, 13 of 109 patients died. The estimated 5-year overall survival (OS) of the entire cohort was 88.1% (95%CI 81.1%-91.4%) with no difference among the MUD, MMUD and MMRD cohort (93.2%, 84.1% and 85.7%, respectively, P=0.361) .@*Conclusion@#These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It’s reasonable to consider AD HSCT as first line therapy for SAA children without matched sibling donor. Better strategies are required to prevent GVHD.
ABSTRACT
<p><b>OBJECTIVE</b>To enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS).</p><p><b>METHOD</b>Next-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015).</p><p><b>RESULT</b>Three patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%.</p><p><b>CONCLUSION</b>NGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.</p>