Academic literature on the topic 'Bone like-inducing graft'

Abstract Donor leukocyte infusion (DLI) can induce graft-versus-leukemia (GvL) reactions in patients with chronic myeloid leukemia (CML) relapsing after allogeneic bone marrow transplantation (BMT), but the mechanisms of the antileukemic effect of DLI are unknown, and the procedure is complicated by graft-versus-host disease (GvHD) and graft failure. Here, we adapted a murine retroviral BMT model of Philadelphia+ leukemia by combining allogeneic bone marrow (BM) from C57Bl/6 (H-2b) mice with BCR-ABL–transduced Balb/c (H-2d) BM, inducing mixed chimerism and myeloproliferative disease in recipients resembling relapse of CML following allogeneic BMT. Infusions of allogeneic splenocytes eliminated BCR-ABL–induced CML-like disease in the majority of mixed chimeras, with significant GvL effects mediated by both CD4+ and CD4- cells. BCR-ABL–induced acute B-lymphoblastic leukemia was also eradicated by DLI in major histocompatibility complex (MHC)–mismatched chimeras. Most DLI-treated mice converted to full allogeneic chimerism but succumbed frequently to GvHD or graft failure. When MHC-matched B10.D2 (H-2d) mice were the allogeneic donors, CML-like disease was more resistant to DLI. These results suggest that depletion of CD8+ cells from DLI could impair GvL against CML, while increased MHC disparity between donor and recipient may improve the responsiveness of Philadelphia+ B-lymphoblastic leukemia to DLI.

Hydroxyapatite (HA) doped with trace elements has attracted much attention recently owing to its excellent biological functions. Herein, we use a facile co-precipitation method to incorporate selenium into HA by adding sodium selenite during synthesis. The obtained selenium-substituted HA products are needle-like nanoparticles which have size and crystallinity that are similar to those of the pure HA nanoparticles (HANs) when the selenium content is low. HANs are found to have the ability to induce the apoptosis of osteosarcoma cells, and the anti-tumour effects are enhanced after incorporation of selenium. Meanwhile, the nanoparticles can also support the growth of bone marrow stem cells. Furthermore, the flow cytometric results indicate that the apoptosis induction of osteosarcoma cells is caused by the increased reactive oxygen species and decreased mitochondrial membrane potential. These results show that the selenium-substituted HANs are potentially promising bone graft materials in osteosarcoma treatment due to their dual functions of supporting normal cell growth and inducing tumour cell apoptosis.

Abstract Graft-versus-host disease (GVHD), the major complication of allogeneic hematopoietic stem cell transplantation, is mediated by donor T cells recognizing host alloantigens expressed on antigen-presenting cells (APCs). Total body irradiation (TBI) activates and damages host tissue, produces inflammatory cytokines and damage-associated molecular patterns, and allows translocation of microbial products into the systemic circulation. It has been assumed that these products bind to toll-like receptors (TLRs) on APCs and monocytes/macrophages, activate inflammatory pathways, and further amplify GVHD. On the other hand, TLRs are also expressed on T cells but their roles in the adoptive T cell response remain to be investigated in vivo. TLR signals are mediated by both MyD88-dependent and independent TRIF protein pathways. We evaluated the role of T cell TLR signaling in T cell alloreactivity in a mouse model of allogeneic bone marrow transplantation using mice with defective TLR signaling induced by deletions of the TLR adaptor proteins TRIF and MyD88 (TRIF/MyD88 DKO mice); in these mice, the TLR-dependent signaling pathway was eliminated. Lethally irradiated B6D2F1 mice were injected with 2 × 106 T cells from wild-type (wt) or TRIF/MyD88 DKO mice together with 5 × 106 T cell-depleted bone marrow (TCD-BM) from wt or DKO mice. Morbidity and mortality of GVHD was significantly less in recipients of TRIF/MyD88 DKO T cells than in recipients of wt T cells, irrespective of donor bone marrow type (Table). Reduction of GVHD was not seen in recipients of MyD88−/− T cells or TRIF−/− T cells, suggesting that inhibition of signaling through TRIF or MyD88 alone in donor cells is not sufficient to reduce GVHD. Histopathologic examination of the small intestine, liver, and skin showed significantly reduced GVHD pathology in recipients of DKO T cells (Table). Thus, effects of TLR signaling in donor cells on GVHD primarily reside in the T cell compartment of the donor graft, not in donor accessory cells. In recipients of TRIF/MyD88 DKO T cells, reduction of GVHD was associated with impairment of donor T cell expansion and production of TNF-□ and IFN-□. In marked contrast though, TRIF/MyD88 DKO T cells were activated equally to wt T cells in unirradiated B6D2F1 mice after adoptive transfer, thus activation of DKO T cells was impaired only in recipient mice heavily pretreated with TBI. These results suggest that T cell TLR signaling provides critical co-stimulation for T cells in an inflamed environment. T cell TLR signaling was also required for optimal graft-versus-leukemia activity. These results challenge the current paradigm that TLR functions are primarily attributable to their role in APCs and monocytes/macrophages in GVHD, and reveal a previously unrecognized critical role for T cell TLRs in inducing GVHD and GVL after hematopoietic stem cell transplantation. Pathological scores T BM Survivals(%) Clinical scores Serum IFN □ (ng/ml) Liver Intestine Skin *P<0.05 vs wt, ND; not detected syn syn 100 0.2±0.2* ND 1.0±0.6 1.0±0.0 0.0±0.0 wt wt 27 6.2±0.9 4.3±1.2 18.3±2.3 16.7±3.0 1.7±0.8 wt DKO 25 5.5±0.8 DKO wt 100* 1.8±0.4* 0.4±0.1* 7.9±1.0* 10.9±1.7 0.1±0.1* DKO DKO 88* 2.2±0.4*

Abstract The curative Graft-vs-Tumor effect (GvT) of allogeneic Stem cell transplantation (SCT) is frequently complicated with life threatening Graft-vs-Host Disease (GvHD). In mice, prevention of GvHD, without abrogation of GvT is possible by co-transplantation of naturally occurring regulatory T cells (Tregs) with SC grafts. Consistent with these murine studies, we recently demonstrated that also human Tregs possess potent GvHD-downregulatory capacities in a xenogeneic(x) model, where x-GvHD is induced by infusion of autologous human T cells in RAG2−/−γc−/− mice (Mutis et al. Clin. Cancer Res.2006, 12: 5520–5525). Towards clinical application of Tregs, we now explored the impact of human Treg-administration on GvT in a bioluminescence imaging (BLI) based human-GvT model in the RAG2−/−γc−/− mice. In this model, mice inoculated with luciferase (LUC)-transduced human myeloma (MM) cell lines developed BLI-detectable, progressive, MM-like multifocal tumors exclusively in the bone marrow (BM). Full blown tumors were effectively eliminated by infusion of allogeneic human PBMC. This treatment also caused lethal x-GvHD as expected. In this setting, co-infusion of human PBMC with autologous, in vitro cultured Tregs at a 1:1 Treg: T effector cell ratio had no adverse effects on the development of GvT while significantly reducing the lethality of x-GvHD. In vitro analyses of sacrificed mice at day 21 revealed that administered Tregs homed to BM and spleen, significantly downregulated the total numbers of IFN-γ-producing CD4+ and CD8+ T cells responding to CD3 mediated signals, but had no downregulatory effect on the frequencies of IFN-γ-producing T cells responding to tumor cells. There was also no downregulation of cytotoxic activity against tumor cells in Treg-treated mice. Conclusively, these results showed that Tregs, at doses which are inhibitory for x-GvHD-inducing T cells, could maintain the GvT effect by allowing T cell reactivity against tumor cells. Human Tregs thus still hold promise as attractive cellular tools for separating GvT from GvHD.

Abstract It has been reported that naive CD4+CD62LhiCD44lo T cells induce severe GVHD in a complete MHC mismatched allogeneic model of mouse bone marrow transplantation (BMT), but that effector memory CD4+CD62LloCD44hi T cells obtained from normal donors do not induce GVHD. The lack of GVHD-inducing capacity of effector memory cells from unprimed donors may reflect their lack of previous exposure to host alloantigens. We tested this hypothesis in a complete MHC mismatched allogeneic model of BMT by comparing the ability of effector memory T cells obtained from untreated C57BL/6 donors and donors immunized against host BALB/C alloantigens to induce GVHD. C57BL/6 donors were immunized by injecting 50 x106 host BALB/C spleen cells i.p. and after one week with 10x 106 cells. Both the unprimed and alloantigen primed CD4+ T cells expressed similar levels of lymph node homing chemokine receptor CCR7, and activation markers like CD69 and CD25. We sorted naive (CD62LhiCD44lo) and effector memory (CD62LloCD44hi) CD4+ T cell subsets from C57BL/6 donor mice four weeks after immunization, and compared their alloreactivity to BALB/C in an in vitro MLR. Interestingly effector memory CD4+ T cells from primed mice produced significantly higher levels of IFNγ compared to the effector memory from unprimed donors. We found that CD62LloCD44hi cells from unimmunized donors failed to induce GVHD in 85% of the hosts over 100 days while CD62LloCD44hi cells from immunized donors caused progressive weight loss and death in 100% of hosts (p <0.001). Whereas naive CD4+ T cells from unimmunized donors accumulated rapidly in the lymph nodes and spleen of irradiated hosts, effector memory CD4+ T cells had markedly reduced accumulation in these tissues. Furthermore, at day 6 after transplantation effector memory CD4+ T cells from primed mice, showed hundred fold higher accumulation in the host liver compared to unprimed effector memory donor CD4+ T cells. Long term surviving hosts transplanted with primed effector memory cells showed histopathological features of chronic GVHD in liver characterized by portal tract inflammation and lymphocyte infiltration with bile duct injury. In conclusion, memory CD4+ T cells from donors immunized to host alloantigens are able to induce chronic GVHD , but memory cells from unimmunized donors do not.

Abstract Abstract 1924 Bone is among the most frequently transplanted tissue with about 1 million procedures annually in Europe. Allografts and autografts account for more than 80% of total graft volume, despite their considerable disadvantages, including the risk of disease transfer and immunologic rejection, limited supply of bone, costs and complications. Significant growth opportunities exist for synthetic bone grafts in association with mesenchymal stromal cells (MSC) from autologous or allogeneic sources as alternatives to biological bone grafts in orthopaedic and maxillofacial surgery. The objective of REBORNE is to perform clinical trials using advanced biomaterials and cells triggering bone healing in patients. To reach this goal, five phase I clinical studies with 20 patients have been planned in 12 clinical Centers spread in 8 European countries. Aim of the Immunological Unit of Reborne is to assess the MSC immunomodulatory properties in presence of the biomaterial used as scaffold for MSC delivery. All the functional experiments were performed in parallel, by comparing the effects of standard culture conditions and three-dimensional culture setting using MBCP (Biomatlante). Material and methods: Bone marrow MSC were provided from REBORNE Consortium Centers. To perform proliferation assays, different immune effector cells (T, B and NK cells) were stained with CFSE according to manufacturer's protocol. Active caspase-3 cell staining was used for survival quantification of immune effector cells after co-culture experiments. Differentiation potential was evaluated by culturing MSC with two different media containing either bone morphogenetic protein 4 (BMP4) or dexamethasone. After three weeks, osteogenic differentiation was quantified by qRT-PCR, alkaline phosphatase activity and alizarin red staining. Results: We found that primed MSC, pre-treated with the inflammatory cytokines IFNg and TNFa, displayed upregulation of HLA-ABC, CD54, CD106 and de novo expression of HLA-DR, both in standard culture conditions and in association with MBCP. Immune effector cells could be cultured and collected even in presence of MBCP and no significant differences were found between standard- (MSC + effector cells) and 3D-coculture conditions (MSC + MBCP + effector cells), in terms of immune effector cell proliferation. In both experimental conditions MSC suppressed T and NK cell proliferation (% suppression: MSC + T = 68.4; MSC + MBCP + T = 62.4; MSC + NK = 17.5; MSC + MBCP + NK = 20.2) and increased B cell proliferation (MSC + B = +13%; MSC + MBCP + B = +12.3%). In addition, immune effector cells viability was not affected by MBCP and MSC co-culture increased their survival even in presence of MBCP; in fact, in each culture condition the percentage of inhibition of T, B and NK cell apoptosis was higher than 20% in comparison to immune effector cells cultured without MSC. Dexamethasone and BMP4 were capable of inducing MSC differentiation into osteoblast-like cells, as confirmed by qRT-PCR analysis. We demonstrated that BMP4-based medium led to fully differentiated osteoblasts (Osterix+, RUNX2+, DLX5+ and alkaline-phosphatase+). Moreover, MBCP was more efficient in increasing osteoblastic differention as compared to standard culture conditions, as shown by the higher expression of Osteocalcin and Osterix. These data show that the association of MBCP and MSC does not affect MSC properties and suggest that it could be a treatment of choice of bone defects instead of allograft and autograft transplantation. Disclosures: No relevant conflicts of interest to declare.

Abstract Natural killer (NK) cell alloreactivity based on inhibitory killer immunoglobulin-like receptor (KIR)-ligand incompatibility (i.e., missing KIR ligand) in the graft-vs-host (GVH) direction has been described to favorably influence engraftment, GVHD, and graft-vs-tumor (GVT) effect following haploidentical or matched unrelated HSCT in patients with hematologic malignancies. The degree and effect of KIR-ligand incompatibility has recently been explored following HLA-identical sibling HSCT (Hsu et al., Blood2005;105:4878). Based on a murine model, we developed a clinical trial with a goal of deliberately inducing a GVHD-free mixed chimeric platform following nonmyeloablative conditioning (consisting of equine ATG, cyclophosphamide, thymic irradiation, and a brief course of cyclosporine) and HLA-matched sibling HSCT. Donor leukocyte infusions (DLI) were given as early as five weeks post-HSCT to patients without GVHD in an attempt to achieve a conversion to full donor chimerism (FDC) with the goal of fully capturing GVT effect with little or no GVHD. In this study we hypothesized that KIR-ligand incompatibility in the GVH direction and KIR-ligand compatibility in the host-vs-graft (HVG) direction would reduce the rate of graft failure, decrease the incidence of GVHD, and improve overall survival following HLA-matched sibling HSCT. Fourteen transplant recipients (bone marrow, n=9; peripheral blood stem cell, n=5) with refractory hematologic malignancies (NHL, n=7; HD, n=3; MM, n=2; CLL, n=1; AML, n=1) were analyzed. KIR typing was accomplished using PCR amplified DNA from both donor and recipient patient samples. Typing of the amplified DNA was performed using the Lifecodes KIR-SSO typing kits (Tepnel Lifecodes Corporation). By using the SSO (sequence-specific oligonucleotides) technology in conjunction with the Luminex Instrument, KIR loci were identified for each patient and donor sample. KIR-ligand (HLA) incompatibility in the GVH and HVG directions were assessed based on HLA and KIR genotyping (KIR2DL1, KIR2DL2, KIR2DL3 and KIR3DL1) of 14 donors and 12 of the 14 recipients. Six of the 14 patients eventually lost their grafts despite DLI. Seven patients spontaneously achieved FDC and one converted to FDC following DLI. The missing KIR ligand analysis showed 12 patients (86%, n=12/14) with KIR-ligand incompatibility in the GVH direction (1 missing ligand, n=9; 2 missing ligands, n=3) and 10 patients (83%, n=10/12) with KIR-ligand incompatibility in the HVG direction (1 missing ligand, n=9; 2 missing ligands n=1). The presence or the degree of KIR-ligand incompatibility in GVH or HVG direction was not found to be predictive of spontaneous FDC or graft rejection. There was no significant relationship between the number of missing KIR ligands in either direction and the development of acute or chronic GVHD. This study shows a higher rate of KIR-ligand incompatibility in the GVH (86%) and HVG (83%) directions in the setting of HLA-matched sibling HSCT than previously reported. Although the small number of patients does not allow for statistically meaningful conclusions regarding clinical outcome, the observation of a high incidence of KIR-ligand incompatibility in this population justifies the study of larger patient cohorts to determine the influence of NK cell alloreactivity on transplant outcomes.

Abstract Limitations resulting from the reduced availability of related donors have been solved by the development of haplo-identical transplantation or by the use of cord blood as an alternative source of hematopoietic stem cells (HSC) to the bone marrow or peripheral blood. However, these kinds of transplantation remain associated with an impaired immune reconstitution, leading to an increased risk of infection and require an efficient modulation of post-transplant alloreactivity. In this setting, we and others demonstrated the possibility to control the alloreactivity by suicide gene transfer into donor T cells after ex-vivo T-cell culture. Such ex vivo culture was associated with the acquisition of a memory-like phenotype and with a decreased alloreactivity of gene-modified T cells, leading to an impaired potential of GvHD induction in murine models of allogeneic bone marrow transplantation (BMT). Chen and al. (Blood 2004) showed in an allogeneic BMT murine models that memory T cells were less alloreactive than naive T cells, leading to a less severe GvHD, but improved the immune reconstitution as compared with mice transplanted with bone marrow cells (BMC) only. By analogy with these results, we investigated the potential of ex-vivo expanded T cells (consisting of Con-A-activated splenocytes cultured ex vivo for 12 days in the presence of 500 UI/ml IL-2) to improve immune reconstitution without inducing GvHD. As compared with recipients of T-cell-depleted (TCD) BMC only, the administration of 106ex-vivo-expanded splenocytes (T) from CD45.1 C57Bl/6 mice together with 106 TCD-BMC from CD45.2 C57Bl/6 donors into 8 Gy-irradiated Balb/c allogeneic recipients significantly increased survival of transplanted mice at day 45 (58.3% vs 23.4% for BMC + T vs BMC only; p=0.0012, log rank test). Improved survival was associated with accelerated lymphoid and myeloid reconstitution as evidenced by day 15 lymphocyte and granulocyte blood counts: 212 (median) [range: 15–991]) vs 135 [14–632] lymphocytes/μl (p=0.0220) and 802 [6–5648] vs 114 [5–2411] granulocytes/μl (p=0.0006) for BMC + T (n=61) vs BMC only (n= 55). Importantly, FACS analysis demonstrated that enhanced lymphoid and myeloid reconstitution induced by ex-vivo expanded donor T-cells was due to enhanced donor bone-marrow-derived cells (lymphocyte and granulocyte blood counts: 129 [0–932] vs 11 [0–603] lymphocytes/μl (p=0.0014) and 801 [2–5637] vs 114 [2–2409] granulocytes/μl (p=0.0007) for BMC + T vs BMC only) and not ex-vivo expanded donor cells or residual recipient cells. Within the lymphoid compartment, enhanced reconstitution was observed mainly for CD3+CD8+ cells. Co-infusion of ex-vivo expanded donor T-cells did not induce GvHD (no GvHD-induced mortality or weight loss) while co-infusion of fresh splenocytes from CD45.1 C57Bl/6 mice induced severe GvHD (p<0.001 vs BMC only). Our results establish that ex-vivo expanded donor T-cells have a graft-facilitating effect and that they could be considered as a new cell therapy product allowing improving immune reconstitution after hematopoietic stem cell transplantation. Mechanisms involved in this graft-facilitating effect of ex-vivo expanded donor T cells remain to be elucidated.

Abstract Background Natural Killer (NK) cells have been widely studied due to their non-major histocompatibility complex (MHC)-restricted cytotoxicity towards transformed or virally infected target cells. In the setting of hematopoietic stem cell transplantation (HSCT), donor NK cells may be "alloreactive" as their killer immunoglobuline-like receptors (KIRs) do not recognize their ligands on recipient human leukocyte antigen (HLA) class I molecules (i.e. KIR-ligands), leading to NK activation. NK alloreactivity can often occur in haploidentical HSCT (Haplo-HSCT), by means of KIR/KIR-L mismatch in graft versus host (GvH) direction, contributing to graft-versus leukemia (GvL) effect, clearing residual leukemic blasts. In the last decade, several studies have shown that NK cells alloreactivity plays a role in T-depleted Haplo-HSCT leading to higher disease free survival rates for patients transplanted from NK-alloreactive donors; recent studies have also shown that donors having KIR B haplotypes (characterized by the presence of more activating KIR) or expressing KIR2DS1 correlated with a better clinical outcome of transplantation. Thus, these NK cell features might be positively considered in the donor selection strategy. Materials and Methods: We analyzed NK-alloreactivity in the setting of unmanipulated Haplo-HSCT with post-transplant cyclophosphamide for patients affected by acute myeloid leukemia or myelodisplastic syndromes. 101 consecutive patients transplanted from September, 2010 to October, 2014 were enrolled, with the big majority of donors and patients studied for HLA-genotype and KIR. Results: Disease status at HSCT was the most relevant factor affecting outcome (p <0.0001), with 3 y 78% overall survival (OS) and 76% disease free survival (DFS) rates for "early" patients (CR1+CR2, n=61) versus 33% OS and 28% DFS rates for "advanced" patients (CR3 or active disease, n=40). Nor NK-alloreactivity nor the presence of donor KIR-B haplotype nor the presence of donor KIR2DS1 seemed to play a role in preventing leukemia relapse. NK alloreactive patients had DFS rate similar to non-NK alloreactive group (62% vs 59%, p 0.47) with a better, still non-significant trend in OS (72% vs 60%, p 0.14) for NK-alloreactive patients. Similarly, Haplo-HSCT from donors with KIR-B haplotype (with B-content score>=2) or who had KIR2DS1 was not associated with better outcome (p 0.67 and p 0.89, respectively). We observed an high expression of CD56 and inhibitory receptors such as NKG2A on surface of NK cells in post-HSCT samples, suggesting that NK-cell function could be inhibited in unmanipulated haploidentical setting. Conclusions NK alloreactivity seems not to play a role in preventing leukemia relapse in unmanipulated haploidentical transplantation with post-transplantation. The different immunosuppressive approach of this Haplo-HSCT setting compared to T-depleted Haplo-HSCT, with concomitant use of cyclosporine from early transplant days, which has been shown to interact and possibly inhibit NK cells in vivo, and post transplant cyclophosphamide effects, selectively killing activated T-cell and inducing long-term tolerance, could affect NK efficacy. Further studies are needed to better understand the complexity of this intriguing issue, leading to a more complete definition of NK cell functions in this Haplo-HSCT setting. Disclosures No relevant conflicts of interest to declare.

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.