Application of bronchoalveolar lavage fluid in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10(9)/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion: BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.

Treatment of 30 elderly patients with advanced myeloid neoplasm by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm. Methods: From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively. 18 patients received RIC while 12 patients received MAC conditioning regiments consisted of Busulfan, cytarabine, fludarabine or clarithromycin±TBI, respectively. Results: Five patients died early in the conditioning stage, 24 patients successfully engrafted. The median time of neutrophil engraftment was 14(10-18) d, whereas platelet engraftment was 15(10-19) d. Six cases (25%) experienced aGVHD grades Ⅱ, 8 cases (32%) cGVHD, including moderate to severe cGVHD in 2 cases (8%). Seven, 7 and 5 cases developed CMV viremia, pneumonia and herpeszoster, respectively after transplantation, but no patients died of infections. The median follow-up time of the patients was 7(0.5-38) months. Twenty-one patients were still alive. The estimated 2 years OS and LFS were 62.5% (95% CI 39.2%-85.8%) and 59.2% (95% CI 26.9%-91.5%), respectively. Univariate analysis showed that HCT-CI was the only factor influencing OS. Conclusion: Allogeneic hematopoietic stem cell transplantation could improve the survival of elderly patients with myeloid neoplasm.

Outcomes of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation for 10 patients with myelofibrosis / 中华血液学杂志

Objective: To evaluate the efficacy of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo-HSCT) for patients with myelofibrosis (MF). Methods: The clinical data of 10 patients with myelofibrosis (MF) who underwent RIC-allo-HSCT. Results: Of all 10 patients, 6 were male and 4 women, with a median age of 28.5 (22-54). Using fludarabine/busulfan plus total body irradiation (FB+TBI) pretreatment scheme based. Hematopoiesis reconstitution was achieved in 9 patients (90%). The median time of neutrophil and platelet engraftment was 13.5 (10-22) day and 16.5 (13-40) day, respectively. Acute GVHD occurred in 4 cases while chronic GVHD in 5 cases. The prospective OS for 3 years was (90.0±8.5)% after a median follow-up time of 17 months. Transplant related mortality was 1 case. Conclusion: RIC-HSCT with FB+TBI is a feasible and effective alternative for MF patients.

DNA methyldtion and asthma: Recent progress / 第二军医大学学报

DNA methylation is one of the most common forms of epigenetic modification, and t is closely related to the development of bronchial asthma, but its mechanism is unclear. Without altering the sequences of genes, DNA methylation can transfer the cytosine on the 5 end of CpG dinucleotide into methyl cytosine by DNA methyltransferase. Hence, DNA methylation can regulate gene expression, leading to the development and progression of diseases. In this review, we summarized the roles of DNA methylation in bronchial asthma, including related predisposing factors and mechanisms of action.

Isolated peripheral neuropathy as an unusual presentation for an extramedullary relapse of acute leukemia

A 23-year-old man in remission from acute myeloblastic leukemia after allogeneic peripheral blood stem cell transplantation developed peripheral neuropathy presenting as sciatic and peroneal nerve deficits. Electrophysiological tests localized the lesions to the left sciatic and common peroneal nerve. Magnetic resonance imaging revealed nerve thickening and enhancement, while a positron emission tomography-computed tomography scan demonstrated increased fluorodeoxyglucose uptake tracking along the nerve, suggesting peripheral nerve infiltration. This report demonstrates an unusual presentation of acute leukemia relapse presenting as focal neuropathy

Item function analysis on the Quality of Life-Alzheimer's Disease(QOL-AD)Chinese version, based on the Item Response Theory(IRT) / 中华流行病学杂志

<p><b>OBJECTIVE</b>To introduce the Item Function Analysis(IFA) of Quality of Life- Alzheimer's disease(QOL-AD)Chinese version and to explore the feasibility of its application on Chinese patients with AD.</p><p><b>METHODS</b>Two hundred AD patients were interviewed and assessed by QOL-AD, through the stratified cluster sampling method. Multilog 7.03. was used for Item Function Analysis. Difference scale(a), difficulty scale(b)and Item Characteristic Curve(ICC) of each item of QOL-AD were provided.</p><p><b>RESULTS</b>Different scales of the item 1, 7 were below 0.6, while all the others were above 0.6. As for ICC. The first and last lines for the other items were monotonic in which the two in between were in inverted V-shape, with very steep slopes, except for the item 1 and 7.</p><p><b>CONCLUSION</b>Results form the IFA showed that QOL-AD was applicable to be used in the Chinese patients with AD.</p>

The role of FDG-PET in staging of lymphoma and evaluation of therapeutic efficiency / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the application of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to the staging and detecting residual masses of lymphoma.</p><p><b>METHODS</b>The clinical data of 179 patients with lymphoma were analyzed retrospectively. The results of FDG-PET, computed tomography (CT) and bone marrow biopsy (BMB) were compared for detection of lymph node/extranodal lymphoid tissue and bone marrow infiltration. Therapeutic efficiency was assessed by International Workshop Criteria (IWC) and Revised Integrated International Workshop Criteria (IWC + PET).</p><p><b>RESULTS</b>In the detection of 286 disease focuses in 98 patients before chemotherapy, the sensitivities of FDG-PET and CT were 73% and 70% (P < 0.01) in detecting nodal focus,and 87% and 45% (P < 0.01) in detecting extranodal lymphoma respectively. In detection of 104 lesions in 81 patients after chemotherapy,the sensitivities of FDG-PET and CT were 81% and 55% respectively (P < 0.01), and the specificities were 68% and 33%, respectively (P < 0.01) in detecting residual masses. According to IWC criteria, 33 patients achieved complete response/unconfirmed complete response (CR/CRu) , and 8 (24%) relapsed. Patients with PET-positive residual masses had a relapse rate of 40%, whereas only 21% of those with no such masses relapsed. Based on IWC + PET criteria, 25 patients achieved CR, with a relapse rate of 20%. Both FDG-PET and BMB produced positive results in 133/179 (74%) patients. Twenty-two patients with positive FDG-PET results were not detected by BMB. The sensitivities and specificities of FDG-PET for BM infiltration were 52% and 83%, respectively.</p><p><b>CONCLUSIONS</b>FDG-PET is a high sensitive and specific technique in staging and detecting residual masses of lymphoma.</p>

Comparison of STR-PCR and FISH value for monitoring chimerism after sex-mismatched allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to compare the significance of multiplex short tandem repeat polymerase chain reaction (STR-PCR) and fluorescent in situ hybridization (FISH) for monitoring chimerism after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism of bone marrow or peripheral blood cells from 38 patients was analyzed by STR-PCR and FISH on days 14, 28 and at 3 months after allo-HSCT. The results indicated that on day 14, the complete chimerism (CC) was detected in 14 of 30 cases by STR-PCR and in 8 of 30 cases by FISH (p > 0.05). On day 28, the CC was detected in 26 of 31 cases by STR-PCR and in 15 of 31 cases by FISH (p < 0.01). At 3 months, the CC was observed in 22 of 24 cases by STR-PCR and 17 of 24 cases by FISH (p > 0.05). 14 cases were found to have a graft rejection or relapse among 28 cases which were continuously monitored more than 3 months post the transplants. Donor cell decrease in 9 of 14 cases was proved by FISH alone. It is concluded that FISH is more sensitive than STR-PCR in early monitoring chimerism status of post-transplant and in predicting graft rejection or disease relapse.

Allogeneic hematopoietic stem cell transplantation following reduced intensity conditioning regimen for treatment of refractory leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) following reduced intensity conditioning (RIC) regimen for treatment of refractory leukemia.</p><p><b>METHODS</b>Twenty patients with refractory leukemia received allo-HSCT following RIC regimen consisting of fludarabine plus small or moderate dose total body irradiation (TBI). Graft versus host disease (GVHD) prophylaxis was CsA plus mycophenolate mofetil (MMF) or short-term MTX, or these three drugs combination; CD25 monoclone antibody(McAb) and ATG were also used in some of the patients.</p><p><b>RESULTS</b>Seventeen patients engrafted successfully, the median time for ANC > 0.5 x 10(9)/L was 13 (11 - 17) days, and for BPC > 50 x 10(9)/L 19 (12 -42) days. Detected by short tandem repeat (STR)-PCR, complete donor chimerism was confirmed in 16 patients with a median of 14 (7 -35) days. The incidence of acute and chronic GVHD was 47.1% (8/17) and 38.5% (5/13) respectively. The transplant related mortality (TRM) was 25.0% (5/20), mainly from graft failure, intracranial hemorrhage and severe infection. Up to now, 7 patients relapsed and 9 were alive with leukemia free. The overall survival (OS) at 2 year was (35. 3 +/- 14.2)% for all patients and (52.5 +/- 18.6)% for acute non-lymphocytic leukemia (ANLL) patients.</p><p><b>CONCLUSION</b>Allo-HSCT following fludarabine and TBI based RIC regimen can be used for treatment of refractory leukemia with well tolerance and low TRM and there is a better prognosis for ANLL patients than that for acute lymphocytic leukemia patients.</p>

Clinical significance of dynamic monitoring of cell chimerism following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship of chimerism status of cell subsets with engraftment, occurrence of acute graft versus host disease (aGVHD), graft rejection and disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Chimerism status in peripheral blood (PB) and bone marrow (BM) of 65 patients received allo-HSCT were monitored at regular intervals post-transplant. Fluorescence-activated cell sorter (FACS) was used to sort CD3(+)T lymphocytes in 65 cases, CD3(-)CD56(+)CD16(+)NK cells in 52 cases, CD15(+) granulocytes in 32 cases and CD19(+)B lymphocytes in 20 cases post transplants. The chimerism status of different lineage cells was analyzed by polymerase chain reaction amplification of short tandem repeats (PCR-STR).</p><p><b>RESULTS</b>On day +7, NK-cells donor chimerism (DC 55.5%) was higher than other cell subsets. T lymphocyte was the latest one to reach complete donor chimerism (CDC) with a median on day +21. Patients whose T lymphocytes donor chimerism was more than 70% on day +7 and more than 95% on day +14 had a high risk for acute aGVHD. In all cases except those with ALL, the decreased DC of T lymphocytes were observed before molecular or hematological relapse occurred.</p><p><b>CONCLUSION</b>Serial and quantitative T cell chimerism analysis provides a reliable and rapid screening method for the early detection of engraftment, graft rejection, disease relapse and occurrence of aGVHD, therefore, is a prognostic tool to identify patients at high risk of aGVHD and disease relapse following allo-HSCT.</p>

Evaluation of the subsets of lymphocytes and their activated status in patients with myelodysplastic syndrome / 中国实验血液学杂志

This study was purposed to investigate the clinical significance of the amount and activated status of T cell subsets, B cells, NK cells in peripheral blood from patients with myelodysplastic syndrome (MDS). The proportion of T cells, B cells, NK cells in peripheral blood from 30 patients with MDS and their surface activation markers of CD28, CD45RA, CD45RO, CD69, HLA-DR were analyzed by flow cytometry. Twenty-two patients were in the low risk group (RA + RAS) while eight patients were in the high risk group (RAEB + RAEBT). The result showed that the amounts of T cells (CD3+ cells) in peripheral blood from patients with MDS were lower than those in control group. The amounts of naive CD4+ cells (CD4+ CD45RA+ cells) in MDS patients were lower than those in control. The expression rates of early activation marker (CD69) and late activation marker (HLA-DR) on CD3+ cells in MDS patients were significantly higher than those in control. The abnormalities of the immunologically competent cells were mainly observed in the low risk group (RA + RAS), and were characterized by the high expression rates of CD69+ and HLA-DR+ on CD3+ cells, the decrease of B cell amounts. The amount abnormalities of T cell subsets were mainly observed in high risk group (RAEB + RAEBT), and were characterized by the decrease of CD3+ cells and CD3+ CD4+ CD8- cells (Th cells) amounts without high expression of the CD69 and HLA-DR, the decrease of NK cells amounts. It is concluded that there are the abnormalities of T cell subsets and function in the patients with MDS and may change with disease progression, so the measurement of amount and activated status of T cell subsets in peripheral blood from MDS patients can have predictive role for diagnosis of disease progression and guide of therapy.

Transfection of chk1/2 antisense oligonucleotide to HL-60 cell line increases the apoptotic sensitivity to irradiation / 中华血液学杂志

<p><b>OBJECTIVE</b>To block signal transduction of cell cycle checkpoints by antisense blocking of chk1/2 gene to increase the radiation sensitivity of HL-60 cell line.</p><p><b>METHOD</b>To transfect the HL-60 cell with chk1/2 antisense and sense chain alone and in combination, expose the cells to irradiation at 24 h after the transfection, the chk1 protein change was assayed by Western blot and the cell cycles and annexin V apoptosis rates by FCM.</p><p><b>RESULTS</b>The irradiated apoptosis sensitivity was increased by antisense blocking of chk1 gene in HL-60 cell line, the apoptotic rate was 26.31% being significantly higher than that of the sense blocking (10.34%) (P < 0.05), Furthermore, the G(2)/M phase blocking phenomenon decreased and a synergic effect was observed in antisense blocking both the chk1 and chk2 genes.</p><p><b>CONCLUSION</b>Antisense blocking of chk1/chk2 could increase the apoptotic sensitivity to irradiation.</p>