Extracellular matrix controls insulin signaling in mammary epithelial cells through the RhoA/Rok pathway.

Cellular responses are determined by a number of signaling cues in the local microenvironment, such as growth factors and extracellular matrix (ECM). In cultures of mammary epithelial cells (MECs), functional differentiation requires at least two types of signal, lactogenic hormones (i.e., prolactin, insulin, and hydrocortisone) and the specialized ECM, basement membrane (BM). Our previous work has shown that ECM affects insulin signaling in mammary cells. Cell adhesion to BM promotes insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and association of PI3K with IRS-1, whereas cells cultured on stromal ECM are inefficient in transducing these post-receptor events. Here we examine the mechanisms underlying ECM control of IRS phosphorylation. Compared to cells cultured on BM, cells on plastic exhibit higher level of RhoA activity. The amount and the activity of Rho kinase (Rok) associated with IRS-1 are greater in these cells, leading to serine phosphorylation of IRS-1. Expression of dominant negative RhoA and the application of Rok inhibitor Y27632 in cells cultured on plastic augment tyrosine phosphorylation of IRS-1. Conversely, expression of constitutively active RhoA in cells cultured on BM impedes insulin signaling. These data indicate that RhoA/Rok is involved in substratum-mediated regulation of insulin signaling in MECs, and under the conditions where proper adhesion to BM is missing, such as after wounding and during mammary gland involution, insulin-mediated cellular differentiation and survival would be defective.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

The Role of Whole Body DWI in the Evaluation of Bone Disease in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage.@*METHODS@#The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI- group and DWI+ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared.@*RESULTS@#The plasma cell percentage of the patients in DWI+ group was higher than those in DWI- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI+ group were significantly higher than those in DWI- group and normal control group. The ADC values of each part of the patients in DWI- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ.@*CONCLUSION@#DWI+ in MM patients is related to higher tumor invasion. The ADC values of the DWI+ group are higher than those of the DWI- group; the bone ADC values of the DWI- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Interpretation of ASTCT Consensus Responses by Chimeric Antigen Receptor T Cell Therapy CRS/ICANS--Review / 中国实验血液学杂志

Chimeric antigen receptor T cell (CAR-T) therapy was awarded as the largest research breakthrough in 2017 by the American Society of Clinical Oncology, at present, it is rapidly becoming the most promising new treatment for hematological malignancies. However, this therapy also produces a new challenge: toxic adverse events such as cytokine release syndrome (CRS) and neurotoxicity, partial of them can bring death to the patients. The incidence and severity of the above toxic events in different multi-center trial reports are also different, which may be attributed to the different in the considerably variable assessment and grading of toxicities between clinical trials and across institutions. The ASTCT published at 2018 advanced the consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells, it was focusing on CRS and neurotoxicity associated with immune effector cells. In order to provide reference for the development of relevant work in this field and the formulation of security strategies in our country, the main content of the consensus was summarized briefly.

Application of Conditioning Regimen with Busulfan and Cyclophosphamide in Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the safety and efficacy of BUCY (busulfan and cyclophosphamide) conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 72 MM patients received transplantation in the Hematology Department of the First Affiliated Hospital of Soochow University from May 2012 to June 2015 were retrospectively analyzed. Among them, 36 patients received BUCY conditioning regimen while the others received high-dose melphalan (HDM) conditioning regimen. The complication, post-transplantation hematopoietic reconstitution and efficacy between the two groups were compared.@*RESULTS@#There were no significant differences in sex, age, isotype, stage, induction therapy, mobilization method and proportion of conditioning regimen with Bortezomib between the two groups. The median time of neutrophil engraftment for the patients in BUCY and HDM groups was 10 (8-17) and 10 (9-13) d (P=0.046), and the median time of platelet engraftment was 10 (8-18) and 11 (9-47) d (P=0.017), respectively. The transplant related mortality of the patients in both groups was 2.7%. The CR rates of the patients after ASCT (38.9% and 50.0%) were higher than those before ASCT (27.8% and 19.4%) in the two groups. For the patients in BUCY group, the median follow-up time was 45 (0-61) months. Fifteen patients (41.7%) achieved disease progression. While for the patients in HDM group, the median follow-up time was 52(0-75) months. Twenty-two patients (61.1%) achieved disease progression.@*CONCLUSION@#The BUCY conditioning regimen is a safe and effective therapy for ASCT in patients with MM. Besides, in terms of safety and efficacy, BUCY regimen is not inferior to HDM regimen. BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in MM.

The Effects of Chidamide Combined with Anti-myeloma Drugs on the Proliferation and Apoptosis of Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of chidamide combined with anti-myeloma drugs on the proliferation and apoptosis of myeloma cells.@*METHODS@#The proliferation inhibition of the cells was detected by CCK-8 method, and flow cytometry was used to detected the apoptosis of the cells.@*RESULTS@#Chidamide could inhibit the proliferation of myeloma cells and promote the apoptosis of primary myeloma plasma cells in a time- and dose-dependent manner (P<0.05). In NCI-H929 cell line, chidamide combined with low-dose bortezomib and lenalidomide showed synergistic effect, while combined with dexamethasone and pomalidomide showed additive effect. In MM.1s cell line, chidamide combined with bortezomib, dexamethasone, lenalidomide and pomalidomide all showed synergistic effects.@*CONCLUSION@#Chidamide inhibits proliferation of myeloma cells in a time- and dose-dependent manner and promotes apoptosis of primary myeloma plasma cells. Furthermore, it can enhance the inhibitory effect of anti-myeloma drugs.

Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review / 中华血液学杂志

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

Clinical implication of minimal residual disease monitoring by 10-color flow cytometry in multiple myeloma / 中华血液学杂志

Objective: To evaluate the prognostic significance of minimal residual disease (MRD) monitoring by 10-color flow cytometry in multiple myeloma (MM) patients after treatment. Methods: 150 patients with MM who were admitted to the First Affiliated Hospital of Soochow University from July 2015 to July 2017 were retrospectively analyzed. Clinical data, MRD data monitoring by 10-color flow cytometry and prognosis were analyzed. Results: 39.1% (34/87) patients were MRD negative after induction chemotherapy, and 49.3% (34/69) patients were MRD negative within 1 year after autologous hematopoietic stem cell transplantation (ASCT) . MRD-negative patients after induction chemotherapy or after transplantation have better progress-free survival (PFS) than MRD-positive patients (P=0.022 and P<0.001) . According to the changes of MRD pre-ASCT and after ASCT, the patients were divided into 4 groups: patients with MRD continued negativity,improved from MRD positive to MRD negative, MRD continued positivity, transformed from MRD negative to MRD positive. The two-year PFS of the four groups were 83%, 82%, 44%, 0, respectively, (P=0.002) . Multivariate analysis showed that the level of MRD after induction chemotherapy was an independent factor for PFS (P=0.002) , HR=4.808 (95%CI 1.818-12.718) . Conclusion: Patients with MRD negative after treatment is a better prognosis marker than complete remission or even the best marker, which can evaluate prognosis by combining R-ISS and cytogenetic changes.

Efficacy and Safety of the Induction Therapy with Different Doses of Anthracyclines for Patients with Newly Diagnosed Acute Promyelocytic Leukemia / 中国实验血液学杂志

@#]Objective:To investigate the efficacy and safety of induction regimens containing arsenite, allo-transretinoic acid (ATRA) and anthracyclines of different doses as induction chemotherapy for acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 129 consecutive hospitalized newly diagnosed APL patients from January 2011 to December 2017 were collected and retrospectively analyzed. Sixty-six patients received arsenite, ATRA and anthracyclines of low doses (low dose group), while other 63 patients received arsenite, ATRA and anthracyclines of standard doses (standard dose group), the efficacy and safety were compared and analyzed in 2 groups.@*RESULTS@#There were no statistically significant differences in terms of age, sex, routine blood indexes,LDH level, bone marrow promyelocyte count,prognostic stratification between patients in two groups (P>0.05). During the treatment, WBC count peak and its time point were not significantly different between two groups (P>0.05). Both induction regimens showed good efficacy, the PML-RARα gene conversion rate from positive into negative, the 2-year overall survival rate and disease-free survival rate in the low-dose group were similar to those in the standard dose group(P＞0.05). The recovery time of neutrophils and platelets in the low-dose group was 0 d and 11 d, respectively, which were statistically  significantly shorter than those in the standard dose group (3 d,15 d) (both P=0.000). The median value of platelet and erythrocyte transfusion in the low-dose group was 6.9 U and 4.2 U, respectively, which were statistically significantly lower than that in the standard dose group (8.4 U,6.8 U) (P=0.037，0.000). And the inpatient time in the low and the standard dose groups were 30.98 and 30.71 days, respectively (P=0.770).@*CONCLUSION@#For newly diagnosed patients with APL, the efficacy was similar between induction therapy containing arsenite,ATRA and low dose anthracyclines and the induction therapy containing arsenite, ATRA and standard dose anthracyclines, however, the former appears even safer.

Comparison of haploidentical hematopoietic stem cell transplantation and matched-sibling donor transplantation for the treatment of paroxysmal nocturnal hemoglobinuria / 中华血液学杂志

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion: The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.

Outcomes of allogeneic hematopoietic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria compared to paroxysmal nocturnal hemoglobinuria-aplastic anemia syndrome / 中华血液学杂志

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10(8)/kg in the PNH group and 10.81 (3.96-33.40) ×10(8)/kg in the PNH-AA group (P=0.668) . The median doses of CD34(+) cells infused were 5.00 (3.14-8.42) ×10(6)/kg and 3.57 (1.97-6.17) ×10(6)/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions: allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.

Comparison of the efficacy of decitabine combined with micro-transplantation or priming regimen as consolidation treatment for older patients with acute myeloid leukemia / 中华血液学杂志

Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period. Results: There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ(2)=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively). Conclusion: DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.

Comparison of efficacy of first-line administration of generic dasatinib or imatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia treated by hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+) ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph(+) ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph(+) ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ(2)=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ(2)=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ(2)=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ(2)=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions: First-line administration of generic dasatinib could improve EFS for Ph(+)ALL patients treated by HSCT when compered with imatinib.

Outcome of combination of HLA-haploidentical hematopoietic SCT with an unrelated cord blood unit for 127 patients with acquired severe aplastic anemia / 中华血液学杂志

Objective: To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA). Methods: The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). Results: The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×10(8)/kg in the haploidentical grafts and 2.22 (1.10-7.30)×10(7)/kg in the cord blood units, respectively. The median doses of CD34(+) cells infused were 3.49(1.02-8.89) ×10(6)/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×10(5)/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively. Conclusion: Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.

Clinical characteristics of healthcare-associated infection in initially treated patients with multiple myeloma during the induction period / 中国感染控制杂志

Objective To explore the infection status and clinical characteristics of healthcare-associated infection (HAD in patients initially diagnosed with multiple myeloma(MM) during the induction period.Methods Clinical data of 116 patients diagnosed with MM and initially treated with PAD(bortezomib + adriamycin + dexamethasone)or PDD(bortezomib + liposome doxorubicin + dexamethasone) regimen in a hospital were collected,infection rates and clinical characteristics of patients during the induction therapy period were analyzed statistically.Results Among 116 patients,69 received PAD regimen,and 47 received PDD regimen,infection rates in two groups were 79.7％ and 89.4％ respectively;73 patients received subcutaneous injection of bortezomib,43 received intravenous injection of bortezomib,infection rates in subcutaneous injection group and intravenous injection group were 78.1％ and 93.0％ respectively,difference was statistically significant between two groups(P＜0.05).During the induction period,HAI rate was 83.6％ (n =97),81 patients developed infection during the first course,infection status of 3 patients were not clear due to therapy outside the hospital,the actual infection rate was 71.7 ％ (81/113);infection rate during the second course was 56.6 ％ (64/113);a total of 98 patients completed three therapy courses,infection rate was 43.9％ (43/98);66 patients completed four therapy courses,infection rate was 28.8％ (19/66).With the increase of the therapy course,infection rate showed a downward trend.Infection sites from high to low were respiratory system,skin and mucosa,oral and gastrointestinal system,bloodstream,and urinary tract.Difference in constitute of clinical diagnosis between patients receiving and without receiving prophylactic antifungal agents during chemotherapy period was not statistically significant (P =0.063).Conclusion Infection rate is very high during induction period,the main infection site is respiratory system,clinicians and patients need to pay more attention to the prevention and treatment of respiratory system infection.

Busulfan Combined with Cyclophosphamide as the Conditioning Regimen in Patients with Multiple Myeloma Treated by Autolo-gous Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the safety and efficacy of busulfan (BU) combined with cyclophosphamide (CY) as the conditioning regimen of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The safety and efficacy of the BUCY regimen were evaluated through observing the adverse reactions, recovery of hematopoietic reconstitution, response and survival in 20 patients after auto-HSCT.</p><p><b>RESULTS</b>In 20 MM patients with median age 52.5 (38-66), the neutrophil and platelet counts recovered at 10(8-18) d and 10 (8-17) d after auto-HSCT respectively, the treatment related mortality during 100 days after auto-HSCT was 0, the partial remission (PR) rate decreased from 31.58% to 0 (P < 0.05) after auto-HSCT, only 1 patient was in progression of disease, all patients were alived.</p><p><b>CONCLUSION</b>For patients with MM treated with Auto-HSCT, the BUCY regimen is ideal in safety and response, but the long-term effect still should be observed.</p>

Single center comparative analysis of hematopoietic cell transplantation from alternated donor in patients with hematologic malignancies / 中国实验血液学杂志

<p><b>OBJECTIVE</b>One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, as only 1/4 of patients who require an allogeneic hematopoietic cell transplant will have a HLA-matched sibling donor. Thereby, three alternative graft sources: umbilical cord blood (UCB), haploidentical (hi) related donor and mismatched unrelated donor hematopoietic cell transplantation (MMUDT) are available. This study was purposed to compare the characteristics of umbilical cord blood transplantation(UCBT), haplaidentical (hi) related donor hematopoieetic cell transplantation(hi-HSCT) and MMUDT.</p><p><b>METHODS</b>The clinical date of 93 patients with hematologic malignancies who received UCBT (n = 22), hi-HSCT (n = 42) and MMUDT (n = 29), and the days of hematopoietic reconstration and engraftment, rate of acute graft-versus-host disease (GVHD), relapse rate, and overall survival (OS) were analysed.</p><p><b>RESULTS</b>The median days of hematopoietic reconstitution (WBC>1.0×10(9)) among UCBT recipients were significantly longer than those among hi-HSCT/MMUDT recipients, (19 in UCBT, 12 in hi-HSCT and 12 in MMUDT)(P < 0.001), whereas the median days of full engraftment (STR >95%) among hi-HSCT recipients were longer than those among UCBT/MMUDT recipients (26 in hi-HSCT, 15 in UCBT and 20 in MMUDT, P = 0.028), the implant failure rate of UCBT recipients was higher than others (26% in UCBT, 5% in hi-HSCT, 3% in MUUDT)(P < 0.05). Multivarite analysis demonstrated no apparent differences in the rate of aGVHD (50% in UCBT,57.1% in hi-HSCT and 72.4% in MMUDT) (P = 0.498), and the rate of III-VI aGVHD also was no significant defference (27.3% in UCBT, 28.6% in hi-HSCT and 17.2% in MMUDT)(P = 0.543), the rate of chronic GVHD of UCBT recipients was lowered (19.0% in UCBT, 45.5% in hi-HSCT, 58.3% in MMUDT, P = 0.026). Overall survival at 2 years was 79.9% in UCBT, 80.9% in hi-HSCT and 88.0% in MUUDT (P = 0.097), and the TRM in 100 days was 23.8% in UCBT, 20.0% in hi-HSCT and 11.1% in MMUDT (P = 0.245) respectively.</p><p><b>CONCLUSIONS</b>The UCBT is characterised by lowest rate of cGVHD, but its hematopoietic recostruction is slow; the hi-HSCT has more alternative donors for using in clinic and can achieve post-transplant adoptive cellular immunotherapy, but its TRM has been found to be higher; the first important problem for MMUDT is to decrease the higher incidence of aGVHD and cGVHD.</p>

CD20 Expression in Adult Patients with B-lineage Acute Lymphoblastic Leukemia and Its Prognostic Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the expression of CD20 antigen and clinical characteristics in adult patients with B-acute lymphoblastic leukemia(B-ALL).</p><p><b>METHODS</b>The CD20 expression of 126 acute lympho-blastic leukemia patients in our hospital from July 2009 to July 2012 were determined by flow cytometry. The characteristics, examination results and outcome were analyzed retrospectively. The complete remission rate (CR rate), relape rate, 2-year survival rate and 2-year event-free survival (EFS) of patients with CD20 positive and negative after the first cycle of chemstherapy were compared.</p><p><b>RESULTS</b>Positive rate of CD20 antigen expression in 126 patients was 24.4% (31 cases), negative rate of CD20 antigen expression in 126 patients was 75.6% (95 cases). No significant relationship was found between CD20 antigen expression and sex, age, peripheral blood leucocytes count and chromosomal changes. The relapse rate, 2-year survival rate (OS) and 2-year event-free survival (EFS) of adult patients with B-ALL in CD20 positive and negative groups were 53.3% and 38.0%, 52.1% and 92.3%, 33.7% and 70.8% respectively.</p><p><b>CONCLUSION</b>Expression of CD20 in adult patients with B-ALL did not related with clinical features, but related with poor prognosis.</p>