Nomogram for Predicting Early Mortality after Umbilical Cord Blood Transplantation in Children with Inborn Errors of Immunity.

PURPOSE: Pediatric patients with inborn errors of immunity (IEI) undergoing umbilical cord blood transplantation (UCBT) are at risk of early mortality. Our aim was to develop and validate a prediction model for early mortality after UCBT in pediatric IEI patients based on pretransplant factors. METHODS: Data from 230 pediatric IEI patients who received their first UCBT between 2014 and 2021 at a single center were analyzed retrospectively. Data from 2014-2019 and 2020-2021 were used as training and validation sets, respectively. The primary outcome of interest was early mortality. Machine learning algorithms were used to identify risk factors associated with early mortality and to build predictive models. The model with the best performance was visualized using a nomogram. Discriminative ability was measured using the area under the curve (AUC) and decision curve analysis. RESULTS: Fifty days was determined as the cutoff for distinguishing early mortality in pediatric IEI patients undergoing UCBT. Of the 230 patients, 43 (18.7%) suffered early mortality. Multivariate logistic regression with pretransplant albumin, CD4 (absolute count), elevated C-reactive protein, and medical history of sepsis showed good discriminant AUC values of 0.7385 (95% CI, 0.5824-0.8945) and 0.827 (95% CI, 0.7409-0.9132) in predicting early mortality in the validation and training sets, respectively. The sensitivity and specificity were 0.5385 and 0.8154 for validation and 0.7667 and 0.7705 for training, respectively. The final model yielded net benefits across a reasonable range of risk thresholds. CONCLUSION: The developed nomogram can predict early mortality in pediatric IEI patients undergoing UCBT.

Clinical characteristics of a patient with de novo acute promyelocytic leukemia with JAK2 v617f mutation.

BACKGROUND: The V617F mutation of Janus-associated kinase 2 (JAK2) is common in myeloproliferative neoplasms (MPN). JAK2 V617F mutation can be detected in patients with de novo acute myeloid leukemia (AML), but de novo acute promyelocytic leukemia (APL) with JAK2 V617F mutation is rare. CASE PRESENTATION: We report a case of APL with both the t(15;17) translocation as well as the JAK2 V617F mutation that transformed into MPN (PV/ET). CONCLUSIONS: A de novo APL patient presented initially with JAK2 V617F. After ATRA and ATO dual induction and chemotherapy consolidation, the patient achieved complete remission (CR) with undetectable PML/RARα. However, the JAK2 V617F remained positive, and the patient developed MPN (PV/ET) 22 months later, which responded well to interferon therapy.AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; ATO, arsenic trioxide; BM, bone marrow; CR, complete remission; ET, essential thrombocythemia; Hb, hemoglobin; JAK2, Janus-associated kinase 2; MPN, myeloproliferative neoplasms; PLT, platelets; PMF, primary myelofibrosis; PML/RARα; PV, polycythemia vera; WBC, white blood cells.

Durable Cord Blood Cell Engraftment in a Patient with Severe Aplastic Anemia after a Matched Sibling Bone Marrow Transplantation and an Unrelated Cord Blood Transplantation.

OBJECTIVE: Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34+ cells collected from a matched donor is often lower than expected. To overcome the problem, this study was conducted to combine a matched sibling donor with an unrelated cord blood transplantation for the treatment of a patient with SAA. CASE REPORT: A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34+ cells, an unrelated umbilical cord blood stem cell transplantation (UCBT) with 9/10 HLA matching was subsequently carried out. Successful hematopoietic reconstitution was achieved by the dual transplantation. Unexpectedly, beginning in the fourth month after transplantation, the sibling donor chimerism was transformed to a stable and complete UCB source. CONCLUSION: This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

[Clinical Analysis of Patient with Esophageal Granulocytic Sarcoma Derived from Chronic Myelocytic Leukemia].

OBJECTIVE: To investigate the diagnosis and treatment of esophageal granulocytic sarcoma derived from chronic myelocytic leukemia (CML). METHODS: The clinical manifestations, diagnosis and treatment of 1 case of esophageal granulocytic sarcoma secondary from chronic myelocytic leukemia were retrospectively analyzed and the related literature was reviewed. RESULTS: The patient was a 72-year-old woman with poststernal pain accompanied by general weakness. Gastroscopy was performed in a local hospital. At the same time, the increase of peripheral blood leucocytes was obvious. Under gastroscopy, 1.0 cm×0.5 cm irregular protuberance was found at 28 cm from the esophagus to the incisor teeth, and the surface was covered with erosion and a small amount of blood. Pathological results showed that heterotypic lymphoid cell infiltration, cytoplasmic red staining and more neutrophils were seen. Immunohistochemical staining results showed that AE1/AE3, CK5/6 and p63 displayed squamous epithelium (+); atypical lymphoid cells CD20-, CD23-, CD3-, CD5-, CD79a-, MP0+, Ki-67+ (80%) were observed; FISH examination showed positive expression of BCR/ABL. The patient was further examined on myelogran and was diagnosed as chronic myelocytic leukemia with esophageal granulocytic sarcoma. Imatinib was given orally and the patient was followed up in the clinic. CONCLUSION: Esophageal granulocytic sarcoma is rare in clinic, its clinical symptoms are not specific. Gastroscopy should be routinely screened for esophageal discomfort, and the esophageal granulocytic sarcoma derived from CML is treated according to the therapeutic regimen of the acute transformation of chronic myelocytic leukemia.

eIF3b regulates the cell proliferation and apoptosis processes in chronic myelogenous leukemia cell lines via regulating the expression of C3G.

OBJECTIVE: To investigate the functions of eIF3b in chronic myelogenous leukemia (CML). METHODS: The expression of eIF3b was inhibited by transfecting aspecifically designed shRNA into the CML cell lines of TK-6 and K562. The CCK8 assay was conducted to determine cell viability, and flow cytometry was used to examine the change in the cell cycle and cell apoptosis. RNAsequencing was applied to screen the candidate targets of eIF3b to identify the underlying mechanisms of eIF3b.An in vivo tumour xenograft mouse model was established by injecting shRNA transfected cells into the NCG mice. The tumour size and body weight of mice were monitored every other day. The mice were sacrificed 2 weeks after the tumour cell injection. The expression of eIF3b and target genes in the tumour tissues were determined by immunohistochemical staining and Western blotting. RESULTS: The group with inhibited expression of eIF3b led to about 50% lower cell viability compared with that of the control group (P < 0.05). Flow cytometry suggested that the percentage of increase in apoptotic cells was eight times higher than those in control group for TK-6 and K562 cells (P < 0.05). However, the difference between the cell amounts in the S phase for the experiment and control groups was not significant. After RNAsequencing and further validation via qPCR, C3G was screened as the potential target of eIF3b involved in the cell proliferation and apoptosis of CML cell lines. Subsequent in vivo analysis proved that the inhibition of eIF3b suppressed tumour formation and decreased C3G expression, thereby indicating that C3G was the potential target of eIF3b. CONCLUSION: eIF3b is correlated with the cell proliferation and cell apoptosis of CML. Moreover, eIF3b regulation most probably occurs via regulating the expression of C3G.

Inhibition of eukaryotic initiation factor 3B suppresses proliferation and promotes apoptosis of chronic myeloid leukemia cells.

BACKGROUND: Eukaryotic translation initiation factor 3B (eIF3b) has been reported to be overexpressed in colon, bladder and prostate cancers as well as in glioblastoma. However, there is no report on any correlation of eIF3b gene expression with cell proliferation and apoptosis in chronic myeloid leukemia (CML). OBJECTIVES: In this study, we evaluated the role of eIF3b in cell proliferation and apoptosis in CML. MATERIAL AND METHODS: Samples from patients with CML and CML cell lines were used. Quantitative RT-PCR, siRNA transfection, flow cytometry, and western blot analysis were performed. RESULTS: Quantitative RT-PCR revealed that the expression of eIF3b mRNA in CML patients was higher than that in the non-malignant controls. The proliferation of CML cells decreased after transfection of the cells with siRNA. The proportion of cells in the G1 and S phases in the experimental group decreased after transfection, while the number of cells in the G2/M phase increased, as compared with the control group. The total cell apoptosis percentage in the sheIF3b group (transduction with lentivirus-anti-eIF3b in K562 cells) was higher than the shCtrl group (transduction with empty-vector lentivirus in K562 cells) after transfection. Caspase 3/7 activity was higher and the expression of anti-apoptotic protein BCL-2 was lower in the sheIF3b group than in the shCtrl group after transfection. CONCLUSIONS: Our results suggest that downregulation of eIF3b expression inhibits proliferation and induces apoptosis in CML cells.

[Methylation of CHD5 Gene Promoter Regulates p19Arf/p53/p21Cip1 Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia].

OBJECTIVE: To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19Arf/p53/p21Cip1 pathway. METHODS: Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19Arf, p53 and p21Cip1 was determined by real-time quantitative reverse transcriptase PCR and Western blot. RESULTS: The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P＜0.01), but did not correlate with the patient's sex, age and clinical classification (P＞0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19Arf, p53 and p21Cip1 in AML with CHD5 methylation promoter decreased. CONCLUSION: The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19Arf, p53 and p21Cip1 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19Arf, p53 and p21Cip1 pathway, thus promotes the occurence of AML.

Analysis of peripheral blood T-cell subsets and regulatory T-cells in multiple myeloma patients.

To study the peripheral blood T-cell subsets and regulatory T-cells of multiple myeloma (MM) patients. 48 MM patients and 24 healthy controls were enrolled. Changes in peripheral blood T-cell subsets in the MM patients i.e. CD4+CD25+T cells and CD4+CD25+CD127lowT regulatory cells (CD4+CD25+CD127lowTregs) and in healthy controls were measured using flow cytometry and immunohischemistry. The total T-cells (CD3+) in peripheral blood lymphocyte and auxiliary/induced T-cells (CD3+CD4+ T cell) of the 48 MM patients showed no statistical significance when compared with those of the control group. Suppressor/cytotoxicity T-cells (CD3+CD8+ T cell) increased (p < 0.05). CD4+CD25+T cells and CD4+CD25+CD127low Tregs were significantly higher than corresponding values in the healthy group (p < 0.05). The CD4+/CD8+ T cell ratio of Stage III MM patients was significantly lower than that of the control group (p < 0.05). The CD4+CD25+T cells and CD4+CD25+CD127low Tregs of MM patients in the stable and the progressive stages  were significantly higher than those of MM patients in the control group (p < 0.05). The abnormality of the peripheral blood T-cell subset, increased expression of CD4+CD25+CD127low Tregs, and low cellular immunity of MM patients are related to clinical staging and progression of the disease. The quantity of CD4+CD25+CD127lowTregs of peripheral blood cells of MM patients could be significantly increased through the inhibition of CD4+ and CD8+T cell activities. CD4+CD25+CD127low Tregs promotes tumor growth through the inhibition of immunologic cell proliferation. Immunological dysfunction based on Tregs cells plays an important role in the pathogenic course.

Late Relapse of Multiple Myeloma with Testicular Plasmacytoma after Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Review of the Literature.

High-dose chemotherapy combined with autologous hematopoietic stem-cell transplantation (ASCT) is the first-line treatment for multiple myeloma. Yet, some patients will relapse. Testicular plasmacytoma which rarely happens can be isolated or associated with progressive multiple myeloma. Here, we report a case of multiple myeloma (MM) undergoing ASCT when the patient obtained complete remission. He developed painless right testicular swelling after nearly 3 years since the ASCT. After radical orchiectomy, histopathology showed diffuse abnormal plasma cells infiltration of the testicular tissue. At the same time, he experienced a bone marrow relapse, and relapse of multiple myeloma with plasmacytoma of testis was confirmed. It is also important to note that at the time of initial diagnosis with MM, he had no mutation of TP53 and MYC in FISH, but at a relapse with testicular plasmacytoma, some high-risk karyotypes were detected, including amplification with 1q21 and absence of p53, RB1/D13S319 and rearrangement with IGH. Similarly, the rearrangement with IGH was found in the histological sections of testicular neoplasm by FISH. The clinical characteristics and altered chromosomes of the case are discussed in the context of previous reports. In common with reports, testicular plasmacytoma with relapsed multiple myeloma had a worse outcome and our findings suggest that chromosome monitoring can be added in multiple myeloma after ASCT.

WITHDRAWN: Inhibition of eukaryotic initiation factor 3B suppresses cells proliferation and promotes cells apoptosis in chronic myeloid leukemia.

Ahead of Print article withdrawn by publisher..

[Advances in Diagnosis and Treatment of Primary Breast Lymphoma -Review].

Primary breast lymphoma(PBL) is a rare and unique type of lymphoma. Female patients are the majority, but its pathogenesis is not clear, and the estrogen may be related with the pathoganesis. Women who have breast implants have more chance to be suffered. The painless breast masses are the most common clinical manifestations, which is similar to breast cancer. Surgical resection of the mass and core needle biopsy are helpful for the diagnosis. The most common pathological type of PBL is diffuse large B cell type, with non GCB type, and it is prone to extranodal relapse in which central nervous system relapse is common which has poor prognosis. Therapy combined with surgery, chemotherapy and radiotherapy are requied, but rituximab added failed to improve its survival. Small molecular targeted drugs may be beneficial to PBL. In this article, the pathogenesis, clinical characte ristics, diagnosis and treatment of PBL are briefly summarized.

[Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation for Treating Patient with Primary Cutaneous Î³Δ T Cell Lymphoma].

OBJECTIVE: To investigate the clinical characteristics of primary cutaneous Î³Δ T cell lymphoma and its treatment methods. METHODS: The clinical data and treatment process of one woman case of primary cutaneous γ Δ T cell lymphoma diagnosed in our department were analysed. The multiple subcutaneous nodules were the main clinical features, the diagnosis of primary cutaneous Î³Δ T cell lymphoma was comfired by skin biopsy pathology. The immunophenotypes of lymphocytes showed CD20-, CD3+, CD4-, CD8-, CD56+, TIA-1+, Ki-67+ (about 60%); plasma cells kappa+(part)/lambda predominate+(part); histocytes CD4+, CD68/PGM1+; ßF1-, epstein-barr (EB) virus showed negative EBER in situ hybridization. RESULTS: By means of the chemotherapy regimens containing L-Asparaginase, the complete remission (CR) was achieved. Then, the patients were given autologous hematopoietic stem cell transplantation. Neutrophils were implanted after 16 days, and platelet was implanted after 18 days. Now, the patient is still in remission. CONCLUSION: primary cutaneous Î³Δ T cell lymphoma is rare and easy to be misdiagnosed. This disease is aggressive and its prognosis is poor. The large dose chemotherapy with L-asparaginase shows a certain curative efficacy, the autologous hematopoietic stem cells can prolong survival time of the patient.

[Clinical and Pathological Analysis of 9 Patients with Primary Breast Diffuse Large B-cell Lymphoma].

OBJECTIVE: To explore the clinical features, diagnosis and treatment of primary breast diffuse large B- cell lymphoma (PBDLBCL). METHODS: Clinical records of 9 PBDLBCL patients treated in Department of Hematology of Yijishan Hospital Affiliated to Wannan Medical College from August 2001 to January 2014 were analyzed retrospectively. RESULTS: All of the 9 patients were female, with an average age of 48 years (range 28 to 75), 8 cases had unilateral breast tumors and 1 case had bilateral. According to the Ann Arbor stage standard, 2 cases were of stage IE and 7 were IIE. None of them was concurrent with B symptoms; 6 cases had IPI (International prognostic Index) score 0 and 3 had score 1. 2 cases belonged to germinal center B cells type (GCB) and 7 belonged to non-GCB. Double-Hit lymphomas were presented in 3 cases. Out of 9 cases, 3 cases were diagnosed by using tubular needle biopsy, 5 cases were diagnosed by using resection of breast mass, and 1 case was diagnosed by using modified radical mastectomy. 1 case received radical mastectomy, 1 case received unilateral breast removal, 1 case gave up, 1 case received mass excision with chemotherapy and radiotherapy, 5 cases received mass excision with chemotherapy and 1 case received central prophylaxis. A complete response (CR) was observed in 6 cases after first-line chemotherapy. The median follow-up time was 18 months (range 0.1 to 150), 3 cases relapsed and 5 cases died. CONCLUSION: PBDLBCL mostly occurs in female. The main pathological type is non-GCB coupled with Double-Hit lymphoma. Tubular needle biopsy offers benifit in the diagnosis of PBL, R-CHOP or R-CHOP combined with chemotherapy/radiotherapy produce best outcome among all the treatments. Intrathecal injection of chemotherapy drugs may help to prevent recurrence of PBL central.

In vitro degradation, hemolysis, and cytocompatibility of PEO/PLLA composite coating on biodegradable AZ31 alloy.

Magnesium and its alloys have large potential as degradable and absorbable biomaterials because of their mechanical properties and biocompatibility. However, their corrosion resistance is usually inadequate especially in physiological environment, which limits their broad applications in biomedical areas. In this work, plasma electrolytic oxidized/poly(l-lactide) (PEO/PLLA) composite coating was successfully fabricated on biodegradable AZ31 alloy by combing PEO process and sealing with PLLA. The microstructure, elemental composition, and phase composition of the PEO/PLLA composite coating were investigated. The in vitro degradation of the PEO/PLLA composite coating in simulated body fluid (SBF) was also systematically evaluated. The results revealed that the PEO/PLLA composite coating improved the corrosion resistance of AZ31 alloy significantly. The corrosion potential shifted from -1.663V to more positive position -1.317 V and the corrosion current density was reduced with six-order of magnitude. The Mg(2+) ions, hydrogen release, and pH value change of solution caused by degradation were all decreased significantly. Moreover, the PEO process played a critical role in sustaining the integrity of the implant in long-term service. The result of hemolysis test showed that the PEO/PLLA composite coating vested AZ31 alloy a low hemolysis ratio (0.806 ± 0.771)%, which is much lower than the safe value of 5% according to ISO 10993-4. For the cytocompatibility test, compared with bare AZ31 alloy and PEO coating, MC3T3-E1 cells showed much better adhesion and proliferation on the PEO/PLLA composite coating with nearly 4-fold increase of cells after 7-day cultivation, indicating that the PEO/PLLA composite coating has good biocompatibility for biomedical applications.

Hemocompatibility and selective cell fate of polydopamine-assisted heparinized PEO/PLLA composite coating on biodegradable AZ31 alloy.

Biodegradable magnesium and its alloys have attracted much attention, as they have been used as cardiovascular stents recently because of their biodegradation after implantation. However, their corrosion resistance, hemocompatibility and surface biocompatibility are needed for practical applications. In this work, heparinization of the plasma electrolytic oxidation/poly(l-lactic acid) (PEO/PLLA) composite coating on biodegradable AZ31 alloy was achieved by the strong adhesion of mussel-inspired polydopamine (PDAM). The corrosion resistance of the coated substrates was evaluated in simulated body fluid. In particular, the hemolysis ratio and platelet adhesion tests were conducted to evaluate the hemocompatibility of the composite coatings. The in vitro cytotoxicity of the composite coatings was evaluated with human umbilical vein endothelial cells (HUVECs). The adhesion and proliferation of HUVECs and human umbilical artery smooth muscle cells (HUASMCs) directly incubated on the composite coatings were also investigated. The results showed that although PDAM modification and further heparinization reduced the corrosion resistance of the PEO/PLLA composite coating, the protection of the coating for the substrate was mainly maintained. Moreover, PDAM modification and further heparinization significantly suppressed the adhesion of platelets and had little influence on sustaining a low hemolysis ratio thus resulting in good surface hemocompatibility of the composite coating. The in vitro cell test demonstrated that none of the composite coatings presented obvious cytotoxicity. Significantly, after surface heparinization, the composite coating became more suitable for HUVEC growth and simultaneously inhibited HUASMC growth. The results show that further modification of the PEO/PLLA composite coating on biodegradable magnesium alloy is a promising method to obtain good surface hemocompatibility for anticoagulation and to regulate the cell fate for fast re-endothelialization while sustaining the corrosion resistance of biodegradable magnesium-based cardiovascular stents.