Advances in Pathobiology of Primary Central Nervous System Lymphoma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Primary central nervous system lymphoma (PCNSL) is a specific type of non-Hodgkin lymphoma with poor prognosis. The rare incidence of this disease and difficulty to obtain sufficient tissue material impede deep research into PCNSL. However, application of modern molecular techniques makes it possible to find biological characteristics exclusive to PCNSL. Therefore, we systematically reviewed the latest research progress on biological characteristics and pathogenesis of PCNSL.</p><p><b>DATA SOURCES</b>The data analyzed in this review were from the articles listed in PubMed database.</p><p><b>STUDY SELECTION</b>Articles focusing on the biology of PCNSL at the cytogenetic or molecular level were reviewed, including clinical, basic research, and review articles.</p><p><b>RESULTS</b>With respect to histopathology, perivascular growth pattern and reactive perivascular T-cell infiltration are regarded as typical histopathological manifestations of tumor cells in PCNSL. Moreover, tumor cells of PCNSL predominantly express an activated B-cell-like phenotype, including CD10- BCL-6+ MUM1+, CD10- BCL-6- MUM1+, and CD10- BCL-6- MUM1-. On the molecular level, some molecular and genetic alterations may contribute to malignant transformation, including mutations of proto-oncogenes and tumor suppressor genes, gains and losses of genetic material, as well as aberrant activation of some important signaling pathways, such as nuclear factor-κB and JAK/STAT pathway.</p><p><b>CONCLUSIONS</b>The integrated molecular mechanisms involved in pathogenesis of PCNSL are not well understood. The important biomarkers indicating prognosis are not identified. Multicenter studies should be carried out to elucidate pathogenesis of PCNSL to find novel and effective therapeutic strategies.</p>

Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation Using Tumor-ablative Conditioning Regimen for Patients with Refractory/Relapsed Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) using tumor-ablative conditioning regiment for patients with refractory/relapsed non-Hodgkin's lymphoma.</p><p><b>METHODS</b>The clinical data of 16 patients with refractory/relapsed non-Hodgkin's lymphoma received above-mentioned therapeutic regimen from January 2013 to July 2015 was analyzed retrospectively, and conditioning-related toxicity, engraftment, infection, relapse and survival rate were evaluated.</p><p><b>RESULTS</b>No conditioning-related organs' failure and mortality were found. Only 1 patient had not been engrafted, and the engraftment rate was 93.7%. The incidence of serious infection was 31.2%. The median follow-up was 20.5(1-30) months, and 3 patients died, out of them 2 patients died of relapse. Two year overall survival (OS) , disease-free survival (DFS) and relapse rates were 80.2%, 74.5% and 20.6% respectively.</p><p><b>CONCLUSION</b>Auto-HSCT using tumor-ablative conditioning regimen is safe and effective for patients with refractory/relapsed non-Hodgkin's lymphoma, and it possess a certain effect for reducing disease relapse after transplantation.</p>

Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic Syndrome-RAEB and Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy and side effects of treating patients with myelodysplastic syndrome-RAEB (MDS-RAEB) and with refractory acute myeloid leukemia (AML) by using decitabine combined with CAG regimen.</p><p><b>METHODS</b>Clinical data of 21 patients with MDS-RAEB or refractory AML from July 2011 to July 2014 were analyzed retrospectively. Among 21 patients there were 4 cases of MDS-RAEB and 17 cases of refractory AML; 12 cases were beyond 60 years old; 13 cases had high-risk karyotypes. All the patients received decitabine combined with CAG regimen consisting of decitabine 20 mg/(m(2) · d), d 1-5; aclarubicin 10 mg/d, d 6-13; cytarabine 20 mg/d, d 6-19; G-CSF 300 µg/d, d 6-19.</p><p><b>RESULTS</b>After 1 cycle of treatment with DCAG regimen, the outcome of 21 patients showed that 8 cases achieved complete remission (42.1%), 8 cases achieved partial remission (42.1%), 2 cases achieved hematologic improvement, 1 cases achieved non-remission and 2 cases died; and the 1 year overall survival rate was 67.5%. The outcome of 12 patients beyond 60 years old showed that 6 cases achieved complete renission (60%, 6/10), and the 1 year overall survival rate was 62.5%. The outcome of 13 patients with high-risk karytype showed that 6 cases achieved complete renission (54.5%, 6/11), and the 1 year overall survival rate was 61.5%. The main adverse event was myelosuppression, and non-hematological toxicity included liver dysfunction and gastrointestinal tract reaction.</p><p><b>CONCLUSION</b>Decitabine combined with CAG regimen is effective and safe for treatment of MDS-RAEB and refractory AML patients, which can prolong lives of patiens with refractory hematological diseases.</p>

Clinical observation of haploidentical-hematopoietic stem cell transplantation combined with human umbilical cord-derived mesenchymal stem cells for severe aplastic anemia-II / 中国实验血液学杂志

This study was purposed to investigate the efficacy and safety of haploidentical hematopoietic stem cells (allo-HSCT) transplantation combined with human umbilical cord-derived mesenchymal stem cell infusion (hUC-MSC) for severe aplastic anemia-II (SAA-II). Eight SAA-II patients received haploidentical allo-HSCT, the G-CSF mobilized peripheral hematopoietic stem cells and bone marrow haploidentical hematopoietic stem cells were selected as graft, the human umbilical cord-derived mesenchymal stem cells (hUC-MSC) were infused as the third party. Conditioning regimen consisted of rabbit anti-thymic lymphocytes protein(ATG), cyclophosphamide(CTX) and fludarabine(Flu). For two patients out of 8 SAA-II patients the conditioning regimen was combined with busulfan(BU). The graft versus host disease(GVHD) was prevented with CSA, MTX, ATG, CD25 and mycophenolate mofetil. The results showed that the average number of nucleated cells were 9.13×10(8)/kg, and number of CD34(+)cells were 3.76×10(6)/ kg. All the 8 SAA-II patients achieved hematopoietic reconstitution. The average time of neutrophils count>0.5×10(9)/L was 11.9 days, and average time of Plt level >20×10(9)/L was 14.6 days. The incidence of acute GVHD of I-II grade was 25%, and that of III-IVgrade was 12.5%, the transplantation-related mortality was 25%. It is concluded that haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA.

Transplantation of umbilical cord mesenchymal stem cells combined with haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed myeloid leukemia / 中国实验血液学杂志

This study was purposed to analyse the clinical efficacy of transplantation of umbilical cord mesenchymal stem cells (UC-MSC) combined with haploidentical hematopoietic stem cells (haplo-HSCT) for patients with refractory/relapsed myeloid leukemia. The clinical data of 36 patients received transplantation of UC-MSC combined with haplo-HSCT from January 2007 to June 2013 were summarized retrospectively, the engraftment, GVHD and 2 years-overall survival (OS) were analysed. The results showed that the median times of neutrophil count>0.50×10(9)/L and platelet count>20×10(9)/L were 12.0 days and 14.0 days, respectively. Grade III to IV aGVHD occurred in 5 out of 36 patients (13.8%). cGVHD occurred in 12 out of 32 patients (37.5%) and extensive cGVHD occurred in 2 patients. Additionally, only 3 patients (8.3%) experienced relapse. The 2-year OS rate of patients was 76.9%. It is concluded that the transplantation of UC-MSC combined with haplo-HSCT has good therapeutic efficacy for patients with refractory/relapsed myeloid leukemia, and may be served as a therapeutic method especially for patients with high risk and without well matched donor.

Clinical study on recombinant humanized anti-CD25 monoclonal antibody used for treating steroid-resistant acute graft versus host disease following allo-hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to investigate the efficacy and feasibility of recombinant humanized anti-CD25 monoclonal antibody for treating steroid-resistant acute graft-versus-host disease (aGVHD ) following allo-hematopoietic stem cell transplantation (allo-HSCT) . Twenty-one cases with II-IV grade steroid-resistant aGVHD after allo-HSCT were treated by intravenous injection of recombinant humanized anti-CD25 monoclonal antibody at a dose of 1 mg/(kg·d) on days 1, 4, 8. Injection was repeated after 1 week for the patients who did not achieve CR. The results indicated that 13 cases (61.9%) got complete response (CR), 4 cases out of them have been still in disease-free survival, 8 cases have been in survival with mild cGVHD, 1 cases died from AML relapse, 6 cases (28.57%) got partial response (PR), 3 cases out of them have been in survival with mild cGVHD, 3 case died from pulmonary infection, 2 cases without response died from GVHD. Overall response rate was 90.5% and long term survival rate was 71.48%. There were no infusion-associated side-effects after treatment with recombinant humanized anti-CD25 monoclonal antibody.It is concluded that recombinant humanized anti-CD25 monoclonal antibody is effective and feasible for treatment of steroid-refractory grade II-IV aGVHD after allo-HSCT.

Efficacy of donor's purified CD34(+) cells for treatment of poor graft function following allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to evaluate the efficacy and safety of donor's purified CD34(+) cells for treatment of secondary poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Ten patients suffering from secondary PGF after allo-HSCT in our hospital from January 2009 to December 2011 were treated with the donor's purified and G-CSF mobilized CD34(+) cells. All the patients were observed for infusion-related complication and survival status. CliniMACS system was used to separate cells, the results of sorting purified and recovery rate were calculated and statistically analysed. The results showed that the purified of CD34(+) cells reached to (89.31 ± 1.73)%, and the recovery rate reached to (93.27 ± 8.14)%; 10 patients in the process of infusion did not suffer from seriously adverse complications, all of them obtained hematopoietic recovery, neither GVHD nor infection occurred after infusion of donor's purified CD34(+) cells. It is concluded that using CliniMACS system for donor's peripheral CD34(+) separation, both the purified and recovery of CD34(+) cells are satisfied, and the infusion of donor's purified CD34(+) cell is a safe and effective method to treat secondary PGF after allo-HSCT.

The study on freezing intercostal nerves for the relief of postoperative chest pain / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the best freezing time and the optimum analgesia modality.</p><p><b>METHODS</b>In dogs, intercostal nerves were froze at -70 degrees C at different time including 30, 60, 90, 120, 180 s. Samples were got at the operative day, in 10 days and 60 days respectively, then carried on the pathology exam. In clinical study, 150 patients undergoing thoracotomy were randomly designated into 5 groups, all patients were recorded the heart rate, blood pressure, SO2, VAS, the dosage of dolantin, and observed the complications and side effects.</p><p><b>RESULTS</b>At operative day, the freezing nerves appeared brown print macroscopically, and presented degeneration, necrosis of the nerve fiber microscopically with more than 90 s. After 10 days, nerves with more than 90 s became thinner than normal. After 60 days, all nerves had no obvious differentiation than normal. In clinical study, both 90 s group and 90 s with PCIA group were significantly better than 60 s group or PCIA group; The VAS of 90 s with PCIA group was significantly lower than 90 s group but had more side effects such as vomiting, nausea.</p><p><b>CONCLUSIONS</b>At -70 degrees C, the freezing time should be no less than 90 s. The freezing intercostal nerves can safely and effectively relieve postoperative chest pain. The effect of analgesia of 90 s with PCIA group is the best, but has many side effects.</p>