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.

Causal inference of gene regulation with subnetwork assembly from genetical genomics data.

Deciphering the causal networks of gene interactions is critical for identifying disease pathways and disease-causing genes. We introduce a method to reconstruct causal networks based on exploring phenotype-specific modules in the human interactome and including the expression quantitative trait loci (eQTLs) that underlie the joint expression variation of each module. Closely associated eQTLs help anchor the orientation of the network. To overcome the inherent computational complexity of causal network reconstruction, we first deduce the local causality of individual subnetworks using the selected eQTLs and module transcripts. These subnetworks are then integrated to infer a global causal network using a random-field ranking method, which was motivated by animal sociology. We demonstrate how effectively the inferred causality restores the regulatory structure of the networks that mediate lymph node metastasis in oral cancer. Network rewiring clearly characterizes the dynamic regulatory systems of distinct disease states. This study is the first to associate an RXRB-causal network with increased risks of nodal metastasis, tumor relapse, distant metastases and poor survival for oral cancer. Thus, identifying crucial upstream drivers of a signal cascade can facilitate the discovery of potential biomarkers and effective therapeutic targets.

[Quantitative Detection and Integrality Analysis of Plasma Circulating Cell-Free DNA in Multiple Myeloma].

OBJECTIVE: To investigate the role of plasma circulating cell-free DNA (cf-DNA) in the screening and diagnosis of patients with newly diagnosed multiple myeloma (MM) and explore the changes of cf-DNA in terms of content and integrality in the assessment of disease in patients treated with chemotherapy. METHODS: Peripheral blood specimens were collected from 35 newly diagnosed MM patients and 18 healthy volunteers, and 13 of the 35 patients who had finished 3 courses of standard induction chemotherapy were selected as follow-up group. The ALU247 and ALU115 fragments were used as the target genes, and the cf-DNA content in the plasma of patients and healthy controls was measured by quantitative polymerase chain reaction (qPCR). The integrality of cf-DNA was calculated by the ratio of ALU247 to ALU115. RESULTS: Both the concentration of ALU247 and ALU115 fragments and the integrality of cf-DNA in patients were significantly higher than those in healthy controls (all P < 0.05). Patients who had underwent 3 courses of induction chemotherapy had significantly decreased concentration of ALU247 and ALU115 fragments and integrality of cf-DNA after treatment (all P < 0.05), and strong positive correlations were manifested between cf-DNA integrality and serum M protein content, as well as proportion of abnormal plasma cells in bone marrow before and after treatment (r =0.703, 0.705). CONCLUSIONS: Cf-DNA has certain positive significance for the screening and diagnosis of MM. Furthermore, cf-DNA may be a synergism or alternative to serum M-protein content and proportion of abnormal plasma cells in bone marrow in assessing the condition, curative effect and prognosis of patients.

Effective treatment with Gilteritinib-based regimens for FLT3-mutant extramedullary relapse in acute promyelocytic leukemia.

OBJECTIVE: Extramedullary relapse (EMR) is rare in acute promyelocytic leukemia (APL) and, there is a lack of information on its management. Current practices for EMR in APL are always to adopt strategies from other subtypes of Acute lymphoblastic leukemia (ALL) and Acute myeloid leukemia (AML). Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated a remarkable effect on EMR in FLT3-mutant AML. Therefore, it is worthwhile exploring if FLT3 mutation can be a therapeutic target and assessing the efficacy of Gilteritinib on FLT3-mutant EMR in APL. METHODS: We described three cases of FLT3-mutant EMR in APL, comprising two isolated EMR cases and one systemic relapse. The patients underwent treatment with Gilteritinib-based regimens based on FLT3 mutation. RESULTS: All three patients achieved complete regression of EMR, and no signs of tumor lysis syndrome during Gilteritinib-based therapy, only patient 1 showed mild granulocytopenia. They all maintained molecular complete remission (mCR) during the follow-up period. CONCLUSIONS: The Gilteritinib-based regimen shows a high and sustained therapeutic effect with minimal adverse effects, and provides a valuable experience for further evaluation in EMR APL patients.

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.

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.

[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.

Interdigitating dendritic cell sarcoma presenting simultaneously with acute myelomonocytic leukemia: report of a rare case and literature review.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare tumor derived from interdigitating dendritic cells. We report the first case of a 64-year-old Chinese woman who was diagnosed with simultaneous IDCS and acute myelomonocytic leukemia (AML-M4). The patient had undergone chemotherapy for breast cancer 6 years previously. Based on the laboratory results, both the IDCS and the AML-M4 in this patient were determined to be of myelogenous origination. Furthermore, a review of 62 IDCS cases (Medline database, key word: IDCS) reported to date revealed that as many as 17 % of the patients had malignant disease and received radiotherapy and/or chemotherapy prior to developing IDCS, and that this group of patients showed worse prognosis compared with counterparts. The patient in the present report showed poor response to four cycles of sequential chemotherapy, and died 6 months after the initial diagnosis.