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.

[Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of 1 case EBV negative extranodal NK/T cell lymphoma (ENKTL) patients. METHODS: The clinical manifestations, diagnosis and treatment of one case ENKTL patients with EBV negative were analyzed retrospectively. RESULTS: A 46-year-old woman diagnosed as positive for exosanal NK/T cell lymphoma (EBER+) in September 2016 was treated by 6 courses of CHOEP regimen chemotherapy and local nasopharyngeal radiotherapy, without regular follow-up review. On March 20, 2020, the patient was admitted to our hospital for multiple rashes and rupture of the right knee joint for morethan 2 months. Histopathology showed inflammatory exudation and necrotic tissue, atypia lymphocytes were observed, and part of them were grew around the blood vessels. Immunohistochemistry showed: heterotypic lymphocytes CD3 (partial +) , CD43+, CD20-, PAX-5-, CD4-, CD8-, CD56+, GrB+, TIA-1+, Ki-67 (10%+) , and chromogenic in situ hybridization (CISH): EBER-, the patient was diagnosed as recurrent NK/T cell lymphoma (nasal type) stage IV B group (CA stage) and skin involvement of NK/T cell lymphoma by combining PET-CT, bone marrow cell morphology, flow cytometry, chromosome karyotype analysis and TCR rearrangement, etc. On April 4, 2020, the patient was treated by CEOP-L regimen (4 courses) and central lymphoma prophylactic intrathecal chemotherapy. PET-CT re-examination showed the patient achieved PR, and the treatment regimen was changed to Gemos-L regimen. CONCLUSION: EBV negative ENKTL is rare in clinic and easy to be misdiagnosed, so it should be distinguished from peripheral T cell lymphoma. This case was treated with EBV positive ENKTL regimen, with good short-term efficacy.

[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.

Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes multiple myeloma resistance through the JAK2/STAT3 pathway.

AIMS: Bone marrow stromal cells (BMSCs) have been reported to interact with multiple myeloma (MM) and exert a vital function of the survival of MM cells. Heme oxygenase-1 (HO-1), a cytoprotective enzyme, has the potential to become a hematological malignancies targeted gene. This study aimed to investigate the role of HO-1 in MM resistance of BMSCs and its possible mechanisms. MAIN METHODS: In this study, the expression of related proteins was detected by RT-qPCR and Western blot. HO-1 expression was regulated by lentivirus transfection. Cell viability and apoptosis were detected by Flow cytometry and CCK-8. Cytokine secretion was assayed by ELISA. The survival and carcinogenic abilities was detected by clone formation assay. KEY FINDINGS: HO-1 expression in the BMSCs of stage III MM patients was substantially increased, compared with that of healthy donors and stage I/II patients. The results of co-culture of BMSCs and MM cells indicated that, the upregulated HO-1 inhibited the apoptosis of co-cultured MM cells, while downregulated HO-1 promoted the chemosensitivity of co-cultured MM cells, moreover, the upregulated HO-1 in BMSCs increased the colony-formation ability of MM cells. This protective capability may be regulated by CXCL12/CXCR4 signaling. High HO-1 expression in BMSCs can promote the phosphorylation of the JAK2/STAT3 pathway, thereby increasing secretion of SDF-1 in BMSCs and activating CXCL12/CXCR4 signaling. In addition, direct contact between BMSCs and MM cells may cause drug resistance. SIGNIFICANCE: These results indicated that the regulation of HO-1 in BMSCs may be a new effective method of MM therapy.

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.

[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.

[Distribution of Pathogenic Bacteria and Its Influence on Expression of BCL-2 and BAX Protein after HSCT in the Patients with Hematological Malignancies].

OBJECTIVE: To investigate the distribution of pathogenic bacteria in the patients with hematologic malignancies received hematopoietic stem cell transplantation (HSCT) and its influence on the expression of BCL-2 and BAX proteins. METHODS: The clinical data of 64 patients with malignant lymphoma (ML) received auto-HSCT from January 2011 to December 2015 in our hospital were analyzed. On basis of post-treansplant infection, the patients were divided into infection group (36 cases) and non-infection group (28 cases). The distribution of pathogenic bacteria in 2 groups was identified, the T lymphocyte subsets of peripheral blood, expression level of apoptotic proteins and C-reaction protein (CRP) in 2 group were detected. RESULTS: Thirty-six strains of pathogenic bacteria were isolated from 36 case of hematological malignancy after HSCT, including 24 strains of Gram-negative bacteria (66.67%) with predominamce of klebsiella pneumoniae (19.44%). The periperal blood CD4+ (t=2.637, P<0.01), CD4+/CD8+ ratio (t=8.223, P<0.01), BCL-2 protein (t=5.852, P<0.05), BCL-2/BAX ratio (t=14.56, P<0.01) in infection group were significantly lower than those in non-infection group, while CD8+ (t=2.285, P=<0.01), CRP (t=39.71, P<0.01), BAX level in infection group were higher than those in non-infection group. The pearson correcation analysis showed that the CD4+/CD8+ ratio in infection group positively correlated with BCL-2/BAX ratio (t=0.341, P<0.05), while serum CRP level in infection group negatively correlated with BCL-2/BAX ratio (t=-0.362, P<0.05). CONCLUSION: The pathogenic bacteria infecting ML patients after HSCT were mainly Gram-negative bacteria. The post-transplant infection can promote the expression up-regulation of related inflammatory factors and apoptotic proteins. The pathogens may be involved in cell apoptisis that provides a new strategy to treat the hematologic malignancies.

Effect of Decitabine Combined with Unrelated Cord Blood Transplantation in an Adult Patient with -7/EVI1+ Acute Myeloid Leukemia: a Case Report and Literature Review.

Patients with relapsed or refractory acute myeloid leukemia (rAML) have a poor prognosis if they do not undergo hematopoietic stem cell transplantation (HSCT). We describe a case herein of acute myeloid leukemia (AML) with monosomy 7 and EVI1(+)(-7/EVI1(+)) in a patient who failed to achieve a complete remission (CR) after two cycles of standard induction chemotherapy. He subsequently received decitabine (DAC) as "bridge therapy" and directly underwent unrelated cord blood transplantation (UCBT) due to the absence of an available sibling donor. Although DAC treatment did not induce CR, it did produce hematologic improvement and control disease progression with acceptable side effects, thus effectively bridging the time of donor search. Following UCBT, the marrow showed complete hematologic and cytogenetic remission. At present, 18 months after the transplantation, the patient's general condition is still good.

[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.