Graft vs Host Disease ; drug therapy ; Humans ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; therapeutic use

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.
Female ; Male ; Humans ; Child ; Retrospective Studies ; Osteomyelitis/drug therapy* ; Arthralgia ; Diphosphonates ; Fever ; Graft vs Host Disease

Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; therapy ; Recurrence

BACKGROUNDMinimal residual disease (MRD)-directedmodified donor lymphocyte infusion (mDLI) is used to treat relapse after hematopoietic stem cell transplantation (HSCT). For patients who experience an unsatisfactory response tomDLI, relapse is usually inevitable. Therefore, we sought to evaluate the efficacy ofinterferon α therapy in these patients.

METHODSRegular MRD monitoring was carried out after the HSCT. The patients who were MRD-positive underwent mDLI. Patients with an unsatisfactory response to mDLI received interferon α therapy (3 million units, twice weekly) with regular monitoring of MRD. To ensure the immunomodulatory effects of interferon α, immunosuppressant treatment would be stopped before interferon α treatment.

RESULTSFive patients with an unsatisfactory response to mDLI treatment received interferon α (3 had t (8;21) chromosomal translocation acute myeloid leukemia, and 2 had common acute leukemia). They had significantly reduced or resolved MRD. Four patients developed chronic graft-versus-host disease. Two of the 5 patients reported transient fevers, and no significant bone marrow suppression was observed. All of them were in continuous complete remission after interferon a treatment. The median survival time was 469 days (range 368-948 days).

CONCLUSIONSIn patients with an unsatisfactory response to MRD-directed mDLI, interferon a may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.

Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Neoplasm, Residual ; drug therapy ; therapy

Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.
Antibodies, Monoclonal/therapeutic use* ; B-Lymphocytes ; Graft vs Host Disease ; Humans ; Immunosuppressive Agents ; Lupus Erythematosus, Systemic/drug therapy*

Graft-versus-host disease (GVHD) is the most common complication after allogeneic hematopoietic stem cell transplantation, and also an important factor affecting the survival and quality of life in patients after transplantation. Currently, immunosuppressive therapy is commonly used for GVHD, but the curative effect is not ideal. How to effectively prevent and treat GVHD is one of the difficulties to be solved urgently in the field of transplantation. In this paper, we summarize the latest progress in pathogenesis, prevention and treatment of GVHD with Chinese medicine (CM). We hope it will provide ideas and methods for exploring the mechanism and establishing a new comprehensive therapy for GVHD with CM.
Allografts ; Graft vs Host Disease ; drug therapy ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Medicine, Chinese Traditional ; Quality of Life

To overcome poor graft function after allogeneic bone marrow transplantation (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is gaining more popularity because of its advantages. There may, however, be an increased risk of graft-versus-host-disease (GVHD) because of the large number of lymphocytes present in a leukapheresis product. An 18-year-old man with severe aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After initial excellent graft take for 8 months, his blood counts gradually decreased to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor mobilized PBSC rescue, the patient's blood counts recovered satisfactorily. Around 1 year after the boost, he developed chronic GVHD that responded to prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055 after PBSC rescue. The present case is the first experience of a long-term follow-up who underwent allogeneic PBSC rescue in Korea.
Adolescence ; Anemia, Aplastic/therapy ; Anemia, Aplastic/blood ; Bone Marrow Transplantation/adverse effects* ; Chronic Disease ; Cyclosporine/therapeutic use ; Female ; Graft vs Host Disease/pathology ; Graft vs Host Disease/etiology* ; Graft vs Host Disease/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Human ; Male ; Prednisolone/therapeutic use

Acute Disease ; Anti-Inflammatory Agents ; therapeutic use ; Budesonide ; therapeutic use ; Child, Preschool ; Graft vs Host Disease ; drug therapy ; Humans ; Intestinal Diseases ; drug therapy ; Male ; Treatment Outcome

OBJECTIVETo compare the efficacy of the Ph⁺ acute lymphoblastic leukemia (ALL)patients treated with combination of tyrosine kinase inhibitors (TKI)and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Ph⁻ ALL patients with allo-HSCT.

METHODSA total of 19 Ph⁺ALL patients were matched with 19 Ph⁻ALL patients from 55 B-ALL patients receiving allo-HSCT in our hospital between January 2003 and August 2014 and were analyzed retrospectively.

RESULTSGender, median age, number of patients with blood white count more than 30 × 10⁹/L, number of patients with meningeal leukemia, disease status before allo-HSCT, period of allo-HSCT, the source of stem cell from donors, HLA disparities between donor and recipient, conditioning regimens and number of infused mononuclear cells and CD34⁺ cells were comparable between two groups of Ph⁺ and 19 Ph⁻ALL patients. The median time of engraftment of neutrophil cells was 12 days versus 13 days (P= 0.284) and that of platelet 14 days versus 17 days (P=0.246), which were comparable between two groups. The estimated 3-year overall survival (OS) in Ph⁺ and Ph⁻ALL groups was (67.5 ± 12.4)% versus (74.3 ± 11.4)% (P=0.434) and 3-year disease free survival (DFS)was (67.8 ± 12.4)% versus (74.3 ± 11.4)% (P= 0.456), respectively. The cumulative incidence of degree Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD)in Ph⁺ and Ph⁻ ALL group was (15.8±8.4)% versus (21.1 ± 9.4)% (P=0.665)and that of degree Ⅲ-Ⅳ aGVHD was (5.6 ± 5.4)% versus (11.5 ± 7.6)% (P=0.541), respectively. The cumulative incidence of cGVHD was (44.1 ± 14.0)% in Ph⁺ALL group versus (44.1 ± 13.0)% in Ph⁻ALL group (P=0.835) and that of extensive cGVHD was (13.1 ± 8.7)% versus (6.2 ± 6.1)% (P=0.379), respectively. The cumulative relapse rate and the cumulative non-relapse rate in both group also have no statistical difference [(10.8 ± 7.2)% versus (20.0 ± 10.7)% (P=0.957) and (23.9 ± 12.4)% versus (7.1±6.9)% (P=0.224), respectively].

CONCLUSIONThe efficacy of Ph⁺ALL treated with combination of chemotherapy and TKIs and followed by allo-HSCT is comparable to that of Ph⁻ALL with allo-HSCT.

Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）. METHODS: From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed. RESULTS: Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×10⁸/kg, and the median CD34⁺ cell number was 11.8×10⁶/kg, ranging in (5.0-18.3)×10⁶/kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%. CONCLUSION Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.
Adult ; Child ; Cyclophosphamide ; Female ; Graft vs Host Disease/drug therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Transplantation Conditioning ; Treatment Outcome