ALBERT

Beschreibung: Abstract 1594 Eosinophils are multifunctional leukocytes implicated in the pathogenesis of numerous inflammatory processes. As the major effectors, eosinophils function in a variety of biological responses, allergic diseases and helminth infections. It is generally accepted human eosinophils develop through a pathway initially sharing common feature with basophils. However, there lacks a clear chart for early development of human eosinophils, such as during embryonic or fetal stages. We recently established an efficient method for producing eosinophils from human embryonic and induced pluripotent stem cells (hESC/iPSCs). By a two-step induction, we first generated multipotential hematopoietic progenitors by co-culturing hESC/iPSCs with mouse AGM-derived stromal cells for 2 weeks. Then, total co-culture cells were transferred into suspension culture favoring eosinophil development with addition of IL-3 and other factors (SCF, IL-6, TPO, Flt-3 ligand) . The maturation of hESC/iPSC -derived eosinophils was shown in a time-dependent manner, first co-expressing eosinophil-and basophil-specific markers [eosinophil peroxidase (EPO), and 2D7, respectively], then the portion of eosinophil markers gradually increased while that of basophil markers decreased (EPO+ cells from 56.4% at day 7 to 94.4% at day 21, while 2D7+ cells from 62.8% to 25.7%, respectively), typically mimicking the development of eosinophils from human adult hematopoietic progenitors. By flowcytometric analysis, an eosinophil-specific surface marker, Siglec-8, was also expressed on these hESC/iPSC-derived eosinophils in a time-dependent manner (from 10.8% at day 7 to 91.3% at day 21), paralleling to those with EPO. The expression of eosinophil-specific granule cationic proteins (EPO, MBP, ECP, EDN) and IL-5 receptor mRNA was also detected by RT-PCR. Furthermore, transmission electron microscopy (TEM) observation confirmed the eosinophil property. Eosinophils derived from hiPSCs hold similar characteristics as those from hESCs. The function of hES/hiPSC-derived eosinophils is being under investigation. Our study provides an experimental model for exploring early genesis of eosinophils, especially in uncovering the mechanisms controlling the development of the initial innate immune system of human being in normal and diseased individuals. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Introduction: In patients with severe aplastic anemia (SAA) who are not candidates for stem cell transplantation (SCT), immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CyA) is the treatment of choice. A randomized controlled trial demonstrated the inferiority of rabbit ATG compared with horse ATG for first-line treatment of SAA (Scheinberg et al. N Engl J Med 365:430-438, 2011). However, horse ATG remains unavailable in many countries outside the USA. In Asian countries, the recommended dose of rabbit ATG ranges from 2.5 to 3.5 mg/kg/day. Here we report the first prospective randomized multicenter study comparing two dosages of rabbit ATG in patients with SAA (www.umin.ac.jp UMIN000011134). Methods: Patients with SAA who required initial IST in Japan (n = 89), China (n = 85), and Korea (n= 48) were enrolled between May 2012 and October 2017. Randomization was 1:1 in blocks between the two dosages of rabbit ATGs. The IST regimen comprised rabbit ATG (thymoglobulin®, 2.5 or 3.5 mg/kg/day for 5 days), CyA (6 mg/kg/day for minimum 6 months), and methylprednisolone (2 mg/kg/day for 5 days) with subsequent tapering of the dose for 28 days. The dose of CyA was adjusted to maintain whole blood trough concentrations between 150 and 250 ng/mL. The primary endpoint was hematologic response at day 180. Secondary endpoints included frequency of Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD), hematologic response at day 360, relapse, and overall survival (OS). Results: In total, 222 patients (age 0.5-71.0 years) were randomized, with 112 patients receiving 2.5 mg/kg and 110 receiving 3.5 mg/kg of rabbit ATG. Patient characteristics were well matched between the two groups. Median follow-up duration for all patients was 742 days from first ATG infusion (range, 16-2165) and 887 days for those surviving till the end of the study (range, 32-1757). After 3 months, in the 2.5mg/kg of rabbit ATG group, 4 (4%) patients achieved a complete response (CR) and 35 (31%) a partial response (PR), for an overall response rate (ORR) of 35%. In the 3.5mg/kg of rabbit ATG group, 1 (1%) patient achieved a CR and 43 (39%) a PR, for an ORR of 40%. After 6 months, in the 2.5mg/kg of rabbit ATG group, 55 patients (49%) achieved an ORR including 7 (6%) who achieved a CR and 48 (43%) PR. In the 3.5mg/kg of rabbit ATG group, 53 patients (48%) achieved a response including CR in 9 patients (8%) and PR in 44 (40%). The response rates did not differ significantly between the two groups at 3 (P = 0.488) or 6 (P = 0.894) months. Multivariate logistic regression analysis identified disease severity [odds ratio (OR), 2.09; 95% confidence interval (CI), 1.18−3.67; P = 0·011] and interval between diagnosis and treatment (OR, 1.86; 95% CI, 1.07−3.22; P = 0.027) as independent predictors of response to IST at 6 months. Despite relatively short follow-up, relapse and clonal evolution occurred with similar frequencies between the two groups, with 4 relapse (among 55 responders) and 1 clonal evolution in the 2.5 mg/kg group and 4 relapse (among 53 responders) and no evolutions in the 3.5 mg/kg group. One patient in the 3.5 mg/kg group developed EBV-LPD at day 109 after IST. During follow-up, 22 (10%) patients died, all of whom showed no response to IST. The causes of death were infections (n = 13), hemorrhage (n = 4), SCT-related complications (n = 2), clonal evolution (n = 1), and unknown (n = 2). Transplantation free survival (TFS), failure free survival (FFS), and OS at three-year were similar between the two groups [TFS, 73% (95% CI, 63%−81%) vs. 71% (95% CI, 60%−80%); P = 0.991; FFS, 45% (95% CI, 35%−54%) vs. 45% (95% CI, 61%−84%); P = 0.909; OS, 85% (95% CI, 76%−91%) vs. 91% (95% CI, 82%−96%); P = 0.107]. Multivariate logistic regression analysis revealed that lack of response to IST was an independent predictor of OS (OR, 6.95; 95% CI, 1.76%−27.46%; P = 0.006). Conclusions: The current study revealed no differences in the efficacy and safety between 2.5 mg/kg and 3.5 mg/kg dose of rabbit ATG for patients with SAA. However, as the follow-up period was relatively short, longer surveillance is warranted to compare long-term complications and survival rates between the two groups in the follow up study. Disclosures Usuki: Daiichi Sankyo: Research Funding; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; Nippon Shinyaku: Speakers Bureau; Ono Pharmaceutical: Speakers Bureau; Novartis: Speakers Bureau; Takeda Pharmaceutical: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; SymBio Pharmaceuticals Limited.: Research Funding; Shire Japan: Research Funding; Sanofi K.K.: Research Funding; Pfizer Japan: Research Funding, Speakers Bureau; Janssen Pharmaceutical K.K: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Research Funding; GlaxoSmithKline K.K.: Research Funding; Celgene Corporation: Research Funding, Speakers Bureau; Boehringer-Ingelheim Japan: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Mochida Pharmaceutical: Speakers Bureau; MSD K.K.: Speakers Bureau. Nakao:Novartis: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Beschreibung: Background Diagnosis of inherited bone marrow failure syndromes (IBMFs) depend on classic clinical manifestation including early onset, physical anomalies, family history of cancer and/or bone marrow failure and chromosome breakage testing (MMC and/or DEB), mutation analyses and bone marrow chromosome analyses. At present, more than 70 pathogenic gene mutations had been identified. However, in some patients, physical anomalies is absent or delayed, and were misdiagnosed as acquired aplastic anemia(AA). Genetic analysis is very important to establish a precise diagnosis, predict cancer risk, direct treatment and genetic counseling. In this study, we focus on the application of next generation targeted sequencing in precise diagnosis of pediatric acquired AA/IBMFs, and the association between genetic abnormalities and clinical and laboratory characteristics. Methods We designed a targeted sequencing assay to test a panel of 417 genes. The panel contain reported gene associated with IBMFs and other diseases need be differentiated. Pediatic patients (≤14 year old) with suspected diagnosis of AA/IBMFs were enrolled. Peripheral blood (PB) DNA was used to genetic analysis and oral epithelia cells or PB DNA from their parents were used to identify somatic mutations and unreported polymorphism. All the results were validated by Sanger sequencing. Results The average coverage of targeted region was 98.15%, and the average sequencing depth was 315.9×. Totally, 283 patients were enrolled, including 176 clinically diagnosed acquired AA, 51 Fanconi anemia (FA), 8 dyskeratosis congenital(DKC), 30 Diamond-Blanckfan anemia(DBA), 15 congenital neutropenia(CN), and 3 congenital thrombocytopenia. Totally, 19% subjects had IBMFs related genetic mutations. In the patients who were clinically diagnosed as acquired AA patients, about 7% had IBMFs related disease-causing genetic mutations. Finally, 7 patients were genetically diagnosed as FA, 2 were DKC, 1 was WAS and 1 was SDS. In patients who were clinically diagnosed as FA, 33.4% had FANC related gene mutations. Telomere associated gene mutations were detected in 75% of clinical diagnosed DKC. For patients clinically diagnosed as DBA and CN, 36.7% and 20% were detected disease-causing mutations. After genetic screening, 2 patients who had been diagnosed as FA were modified as WAS and 1 DBA was modified as SDS. Only 26% genetic diagnosed IBMFs patients had family history of bone marrow failure, leukemia, tumor or physical anomalies. Compared with acquired AA, patients with genetic diagnosed FA were more likely to have physical anomalies of short stature and development retardation, Cafe au lait spots and finger or toe malformation(P

Beschreibung: Objective: Chronic myeloid leukemia (CML) is a rare disease among children. It comprises 3% of childhood leukemias. CML in children is different from CML in adult. Here we analyzed the clinical features and prognosis of pediatric CML in a single institute from China. Methods: A retrospective study was performed by reviewing clinical records of pediatric CML from 2002 to 2019. Results: A total of 48 pediatric CML cases were included in the study, with 35 males and 13 females (M: F=2.7:1). Four cases were diagnosed during 2002~2007, 12 cases during 2008~2013 and 32 cases during 2014~2019. Two (4.2%) patients were in accelerate phase (AP) and other 46 patients were in chronic phase (CP) at diagnosis. Median age of onset was 9y (range 1~17y). The most common symptoms were fever (21.6%), fatigue (14.9%) and cough (10.8%). Median size of spleen under left costal margin was 5cm (range 0~21cm). Median WBC count was 15.7/ul, hemoglobin 9.5g/dL, platelet count 58/ul, neutrophils percentage 56% (range 21~74%), basophils percentage 3% (range 1~16%) and median eosinophil percentage was 2% (range 0~19%). Thirty-five patients had done karyotype examination, and 28 cases (80%) with classical Philadelphia chromosome (Ph+). Other 13 patients without Ph chromosome but with BCR/ABL1 fusion gene. In our study, there were 4 patients treated by hydroxyurea and α-interferon, other 44 patients have been used imatinib (IM) 240-340mg/m2 per day. Median time from onset to diagnosis was 0.7 months (range 1 day~12 months). Median follow-up time was 52 months (range 1~200 months), while the 5-year overall survival (OS) and event-free survival (EFS) are 100% and 89.1%, respectively. Different gender, age at diagnosis, WBC count, platelet count, karyotype show no difference in OS and EFS. Four patients suffered from blast crisis (BC) (2 patients progressed after using hydroxyurea for 1 and 33 months, 2 patients progressed after using IM for 36 and 6 months, respectively). One patient's BCR/ABL1 transcript level was increased in 36 months after first administration of IM and recovered at 48 months by adding IM dosage from 200mg to 300mg per day. According to the European LeukemiaNet (ELN) criteria, 95.5% patients achieved complete hematologic response (CHR), 90.5% patients achieved complete cytogenetic response (CCyR) and 66.7% patients achieved major molecular response (MMR) at 3, 12, 18 months after IM administration, respectively. There was obvious correlation between WBC count at diagnosis and early molecular response (EMR). Median WBC count was 4.8/ul in patients with EMR and 38.1/ul in patients without EMR. Other clinical features, such as gender, age at diagnosis, hemoglobin count, platelet count and size of spleen, make no difference in EMR. Conclusion: This is a retrospective study on pediatric CML. The median age at diagnosis is 9 years old. Most of all patients are CML-CP. 5y OS and EFS are 100% and 89.1%. The CHR, CCyR, MMR at 3,12,18 months after IM therapy are 95.5%, 90.5% and 66.7% separately. Until now there is no sufficient data on efficiency and safety specific to pediatric CML patients. Further clinical investigations through international collaboration are need to help more and more patients to achieve treatment-free remission. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Abstract 881 Trisomy 21, genetic hallmark of Down syndrome, is the most frequent human chromosomal abnormality. Infants and children with Down Syndrome (DS) are known to have some hematological disorders with an increased risk of developing leukemia. Ten to 20% of newborn with DS are diagnosed as neonatal preleukemic status, Transient Myeloproliferative Disorder (TMD), and approximately 30% of TMD patients are predisposed to acute megakaryoblastic leukemia (AMKL). Recently, acquired mutations in the N-terminal activation domain of the GATA1 gene, leading to expression of a shorter GATA1 isoform (GATA1s), have been reported in AMKL and TMD (Wechsler et al., 2002; Mundschau et al., 2003), but neither patients nor mice with germline mutations leading to expression of GATA1s developed AMKL and TMD in the absent of trisomy 21. These findings suggested that trisomy 21 itself directly contributes to the development of AMKL and TMD. However, the role of trisomy 21 in hematopoiesis, particularly in the human fetus remains poorly understood. To better understand the effects of trisomy 21 on hematopoiesis in embryonic stage and leukemogenesis, we employed human induced pluripotent stem cells (hiPSCs) derived from patients with DS (DS-hiPSCs). Six DS-hiPS and 5 hiPS cell lines (control) from healthy donors, which we used here, were all created from skin fibroblasts and reprogrammed by the defined 3 or 4 reprogramming factors (OCT3/4, KLF4, and SOX2, or c-MYC in addition to the 3 factors, respectively). We generated blood cells from DS-hiPSCs and controls with coculture system using murine aorta-gonad-mesonephros (AGM)-derived stromal cell line (Ma et al., 2009). The cells from hiPSCs were harvested at D11 or D12 of coculture and analyzed the presence of hematopoietic markers and the potentials of hematopoietic colony formation. In the experiments using hiPSCs reprogrammed by 3 factors, human CD34 expression in harvested cells from DS-hiPSCs or controls were detected 10.06 ± 4.35% and 3.04%, respectively. CD45 expression of CD34+ cells was small proportion in both DS-hiPSCs and controls. We next examined the hematopoietic colony formation. Both myeloid and erythroid colonies were detected. Number of colonies formed from DS-hiPSCs was 43.7±11.1 to 74.3±11.2 per an iPSC colony. It's approximately 2 to 3.5 folds numbers of control (p-value

Beschreibung: Abstract 5030 Unlike adult myelodysplastic syndrome (MDS), most of children with MDS have hypocellular bone marrow. Thus, distinguishing MDS from aplastic anemia (AA) can be diagnostically challenging in these patients. To clarify the frequency of pediatric MDS and AA with hypocellular bone marrow in eastern Asia, Japanese and Chinese pediatric hematologists and pathologists conducted a review of 100 patients with cytopenia (50 from Japan, 50 from China). Films stained with both peripheral blood (PB) and bone marrow (BM) along with specimens of BM trephine biopsy were available for all of the patients examined. Patients included 45 males and 55 females, with a median age at diagnosis of 9 years (range: 1 to 19 years). A total of 76 patients had pancytopenia at the time of diagnosis, while 23 had bi-cytopenia and 1 had isolated thrombocytopenia. The medium internal from onset to diagnosis was 319(1–4165) days. Most children present with nonspecific symptoms as a result of cytopenia, including pallor(24%), fatigue(11%), petechiae (27%), bleeding (31%), fever (19%) and infections (10%). Hepatosplenomegaly is uncommon. Before diagnosed, 7% of patients had idiopathic thrombocytopenic purpura (ITP) and 8% of patients had other diseases such as asthma, pneumonia and etc. Cytogenetic analyses performed in 75 patients indicated the karyotype was normal in 45 patients, while 4 had trisomy 8, 1 had monosomy 19, and 2 had trisomy 2. Other abnormalities found included t(X;3)(p11.2;q13), add(6)(p21), and +6. The final diagnoses reached by consensus among the hematologists for the 100 patients included AA in 30 cases, refractory cytopenia of childhood (RCC) in 59 cases, and refractory cytopenia with multi lineage dysplasia (RCMD) in 11 cases. The distribution of the subtypes in the Japanese and Chinese cases were 14:16 for AA, 33:26 for RCC, and 3:8 for RCMD, respectively. In 9 of the patients, the hematologists and pathologists could not agree on the final diagnosis. In 5 of these cases, the hematologists diagnosed the patients as AA, while the pathologists diagnosed RCC. We analyzed the difference between pediatric hematologists and pathologists are the quality of bone marrow and biopsy samples' disparity. Overall, our results suggest that there is no difference in the distribution of the MDS subtypes between Japanese and Chinese children. In order to ensure there is a correct diagnosis of childhood MDS, cooperation between hematologists and pathologists is indispensable. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Abstract 4947 Objective: To analyze the clinical features and survival time in patients with refractory cytopenia of childhood (RCC), and to develop a new diagnostic scoring system for RCC. Methods: The clinical information, laboratory findings at primary diagnosis and survival time in 97 non-severe aplastic anemia (NSAA) children diagnosed in August, 2000 to June, 2006 were analyzed retrospectively. According to the criteria for RCC proposed in the 2008 edition of the World Health Organization classification of hematopoietic and lymphoid tissues, diagnosis of these NSAA patients was reassessed. Results: 37/97 cases (38. 1%) were reassessed as RCC, 60/97 cases (61. 9%) were still diagnosed as NSAA. There was no significant differences in distribution of age, gender and chromosomal abnormalities, absolute neutrophil count, PLT, MCV, absolute reticulocyte count, the number of cytopenias and duration from onset to starting treatmeat between RCC and NSAA. All patients received the treatment of CsA and androgen. There was no significant differences in distribution of treatment response. The overall survival (OS) of RCC patients was significantly lower than NSAA patients (P=0. 041) in long-term follow-up. The former had 91. 5% of 6-year prospective survival (PS) and the latter had 96. 5% of 6-year PS. At a median follow-up of 93 months (range 6–138), 2 patients reassessed as RCC progressed into AML-M5 and PNH respectively, while no NSAA patient progressed into clonal diseases. There was significant differences in the distribution of HGB

Beschreibung: Objective: Juvenile myelomonocytic leukemia (JMML) has both the disease characteristics of myelodysplastic syndrome and myeloproliferative neoplasm. Currently, hematopoietic stem cell transplantation (HSCT) is the only possible cure. Most of the newly diagnosed pediatric patients with JMML have high tumor burden, rapid disease progression, and may not tolerate HSCT. This study explored the short-term efficacy of decitabine combined with low-dose chemotherapy in the treatment of JMML before transplantation. Methods: A retrospective analysis of the patient files of 9 cases of JMML was performed from January 2019 to May 2020. All patients were given decitabine 20mg/m2× 5 days, supplemented with a small dose of cytarabine (50-100mg/m2×3~5 days), and/or etoposide (50mg/m2×3~5 days) chemotherapy. Each treatment interval is 3~4 weeks, bridging with HSCT after 3~4 treatment courses. Results: The median age of onset of 9 cases of JMML was 2 years old (0.5~4 y), male to female ratio was 8:1, the median size of spleen was 6.4cm (2.9~9.8cm) under the costal arch, and WBC was 28.03×109/L (7.3~127.69×109/L), monocytes were 9.25×109/L (1.66~15.79×109/L) at diagnosis. There were 8 cases in the high-risk group and 1 case in the low-risk group. Second-generation sequencing results show that 7 cases carried PTPN11 somatic mutations. Five in 9 cases had two kinds of classic JMML mutations, and 1 case had only NRAS mutation. Seven patients had normal chromosomal karyotypes, and 3 patients had abnormal 8, 11, and 18 chromosomes, respectively. Median treatment courses with decitabine are 3 courses (1~5 courses), the response rate of one course is 77.8% (7/9), the response rate of three courses is 80% (4/5), one case from high-risk group achieved complete remission after treated with 4 courses of decitabine and low-dose chemotherapy. The five-month progression-free survival rate was 77.8% (7/9). Conclusion: Treating JMML with decitabine combined with low-dose chemotherapy, can reduce patients' tumor burden, improve the general condition, and obtain approximately 80% clinical response rate. Decitabine combined with low-dose chemotherapy can be used as a treatment option for JMML before HSCT. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Safety and effecacy of decitabine applicated in JMML patients have not been confirmed.

Beschreibung: Background: Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in young children that is classified as a myelodysplastic/myeloproliferative neoplasm and not only characterized by young age, hepatosplenomegaly, thrombocytopenia and monocytosis, but also by molecular aberrations in the RAS-RAF-MEK-ERK signaling pathway and GM-CSF-hypersensitivity. Most children with JMML experience an aggressive clinical course and the only curative treatment option for these children is stem cell transplantation (SCT). Osteogenesis imperfect (OI) is also an orphan inherited monogenic bone fragility disorder that usually is caused by mutations in one of the two genes coding for collagen type I alpha chains, COL1A1 or COL1A2. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities. Current multidisciplinary management could only improve quality of life for patients, including physical therapy, drug treatment and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell or bone marrow transplantation, targeting the specific altered pathway rather than the symptoms, may develop new curative treatments. Here we report a 3-year-old boy who suffered from both JMML and OI, was successfully transplanted and kept presenting an encouraging outcome up to now. Aims:To investigate the possible efficacy and safety of Allogeneic Hematopoietic Stem Cell Transplantation in a boy both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta. Methods:A 3-year-old boy presented with fatigue, fever, petechia and rash in Aug 2019, accompanying with loss of appetite, joint pain and severe hepatosplenomegaly. The boy had a special appearance of short stature and blue sclerae, meanwhile he suffered intermittent eczema and bone fracture twice since he was 2 years old. Similar characteristics were also positive in his grandmother, father and father's sister. The blood cell counts revealed anemia, thrombocytopenia and leukocytosis especially monocytosis. Bone marrow aspirate showed excessive proliferation of myelomonocytic cells and hypersensitivity to granulocyte-macrophage colony-stimulating factor in vitro. Somatic mutation of gene NF1, PTPN11 and COL1A1 were identified by Next Generation Sequencing.Therefore, the little boy was diagnosed with two rare diseases of Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta at the same time. After 4 courses of hypomethylating agents therapy, the boy underwent haploidentical allogeneic bone marrow stem cell transplantation combined with allogeneic single umbilical cord blood transplant in May 2020. The myeloablative conditioning regimen was composed of Decitabine (20mg/m2/day, days -13 to -9), Cyclophosphamide (25mg/kg/day, days -8 and -7), Busulfan(100mg/m2/day, days -6 to -3), Fludarabine (40mg/m2/day, days -6 to -2) and Cytarabine (100mg/m2/day, days -6 to -2). Post-Cyclophosphamide (50mg/kg/day, days +3 and +4), tacrolimus and mycophenolate mofetil were used for prophylaxis of graft-versus-host disease (GVHD). Results:The number of infused TNCs from haplo-bone marrow and cord blood unit was 41.4×10^8/kg and 9.72×10^7/kg, respectively, while the number of infused CD34+ cells was 11.84×10^6/kg and 2.33×10^5/kg, respectively. The boy achieved sustained engraftment of both neutrophils and platelets at 16 days and 24 days, respectively, with complete haplo-donor chimerism of confirmed at 14 days. He developed grade III acute GVHD (skin, gut and liver) and recovered at 39 days after transplant. Clinical symptoms such as rash, joint pain and hepatosplenomegaly got complete remission, and the mutated genes like NF1, PTPN11 and COL1A1 all disappeared at 30 days. At the time of this report, the boy was alive with negative MRD and good quality of life with a follow-up of 3 months after HCT. Conclusion:To our knowledge, this is the first report that a child both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta was cured by allogeneic hematopoietic stem cell transplantation.Our experience suggests that allogeneic bone marrow transplantation may be a novel safe and effective therapeutic strategy for OI patients. Disclosures No relevant conflicts of interest to declare.