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.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

The Expression of WTAP Gene in Acute Myeloid Leukemia and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance.@*METHODS@#74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed.@*RESULTS@#The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients.@*CONCLUSION@#The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.

In vitro study of black phosphorus quantum dot-loaded liposomes for photothermal therapy of cervical cancer / 药学学报

In this study, black phosphorus quantum dots (BPQDs)-loaded liposomes (liposome-BPQDs) were prepared to explore physicochemical properties and photothermal effects on cervical cancer cells. BPQDs were fabricated by ultrasonic method. Liposome-BPQDs were prepared by thin film dispersion. Surface morphology, particle size, zeta potential and Raman spectra of liposome-BPQDs were characterized. The cytotoxicity of the liposome-BPQDs against human cervical cancer cells (HeLa) was examined by CCK-8 assay. Confocal laser scanning microscope (CLSM) and fluorescence microscopy were used to observe the uptake and apoptosis of HeLa cells. The results indicated that liposome-BPQDs were ellipsoidal or spherical under scanning electron microscope, TEM observation showed liposome-BPQDs were about 90-110 nm in diameter. The particle size measurements showed liposome-BPQDs were (104.2±0.35) nm in diameter, and zeta potential were examined to be (-11.3±3.01) mV. The encapsulation efficiency was (84.40±2.13)%.Under natural conditions with outdoor ventilation, temperature range of 25 ℃-34 ℃ and relative humidity of 80%-82%, the photothermal effects of liposome-BPQDs was better and the degradation denaturation of liposome-BPQDs were slower than those of BPQDs. The results also reflected that liposome-BPQDs could be uptaken by HeLa cells easily. After near-infrared laser irradiation, the mortality of HeLa cells rise significantly when the amount of BPQDs reach 20 μg·mL-1. In summary, liposome-BPQDs with high stability exhibited good photothermal effects, which can be expected to be applied to photothermal therapy of cervical carcinoma.

Metabolomics of Chronic Myelogenous Leukemia Based on GC-MS / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the metabolism characteristics, to search for potential biomarkers associated with disease and to explore related metabolic pathways by analyzing the plasma metabolic profile of patients with chronic myelogenous leukemia (CML) through metabolomies.</p><p><b>METHODS</b>Twenty-six newly diagnosed CML patients in the First Affilated Hospital of Soochow University from February 2015 to April 2015, 26 allogeneic hematopoietic stem cell donors as healthy controls and 26 patients treated with tyrosine kinase inhibitors (TKI) to obtain the best efficacy as post-treatment controls were enrolled in this study. All the metabolites of plasma were extracted by Gas Chromatography-Mass Spectrometer(GC-MS) to collect metabolic fingerprint. Multivariate pattern recognition analysis and t test were combined to screen out the metabolic biomarkers at different time points. The receiver operating characteristic curve analysis was used to evaluate the clinical efficacy of metabolites, and the metabolic pathway analysis was performed.</p><p><b>RESULTS</b>Significantly different metabolite expression mode was found seen between CML and healthy control groups. Six changed metabolites in CML were confirmed by multivariate and variate statistical analyses. Compared with the healthy controls, the levels of tetradecanoic acid and glycerol were decreased, the lactic acid, myo-inositol, d-galactose and glycine in CML patients also increased (all VIP>1,P<0.05, AUC>0.7). The plasma metabolites in CML patients after treatment with tyrosine kinase inhibitors (TKI) showed a recovery trend toward to normal levels. The plasma metabolic pathways of CML were mainly related with galactose, pyruvate, glycerolipid, inositol phosphate and glycine, serine and threonine metabolism (all impact value>0.10).</p><p><b>CONCLUSION</b>Significant changes in plasma metabolite levels were found in CML patients. Metabolomics combined with multivariate pattern recognition analysis may be a new tool to assist diagnosis.</p>

Influence of HLA-E polymorphism on cytomegalovirus infection after HLA-matched hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to explore the potential association of HLA-E polymorphism with the incidence of cytomegalovirus (CMV) infection after HLA-matched hematopoietic stem cell transplantation, 119 HLA-genoidentical sibling pairs for HLA-E polymorphism were analyzed, HLA-E DNA was amplified by polymerase chain reaction (PCR), and the amplified DNA products was also sequenced directly after purification to confirm the genotype. The results showed that the homozygous HLA-E*0101/0101 accounted for 20.17%, the homozygous HLA-E*0103/0103 accounted for 27.73%; heterozygous HLA-E*0101/0103 accounted for 52.10%; in homozygous HLA-E*0101/0101 group, 15 cases were infected with CMV and the CMV infection rate was 62.50%; in homozygous HLA-E*0103/0103 group, 16 cases were infected with CMV and the CMV infection rate was 48.48%; in heterozygous HLA-E*0101/0103 group 20 cases were infected with CMV and the CMV infection rate was 32.25%. As compared with the homozygous HLA-E*0101/0101 group, the CMV infection rate in HLA-E*0103 group displays statistical significance (P = 0.0295). The CMV infection rate occurred higher and its significance is statistical (P = 0.0074). It is concluded that the HLA-E gene polymorphism is associated with CMV infection after HLA-genoidentical bone marrow transplantation.

The impact of HLA high resolution typing mismatching of donor-recipient pairs on outcome of unrelated donor hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the impact of various human leukocyte antigen (HLA) high resolution typing mismatching of donor-recipient pairs on prognosis of unrelated donor hematopoietic stem cell transplantation.</p><p><b>METHODS</b>835 donor-recipient pairs of CMDP data from 2005 to 2010 were analyzed retrospectively. HLA-A, B, C, DRB1 and DQB1 typing were performed using SBT, SSOP and SSP methods. The diseases involved in acute myeloid leukemia (AML) (n = 288), acute lymphoid leukemia (ALL) (n = 227), chronic myeloid leukemia (CML) (n = 187), myelodysplastic syndrome (MDS) (n = 52), non-hodgkin's lymphoma(NHL) (n = 25), aplastic anemia(AA) (n = 42) and thalassemia (n = 14). Of 835 donor-recipient pairs, 362 were completely matched, 159 had a mismatch for a single allele, 125 had a mismatch for a single antigen, 95 had mismatched for both single allele and single antigen, 29 were mismatched at double allele, 20 at double antigen, 45 at multiple allele and antigen. The follow-up assessment was completed before March 2011.</p><p><b>RESULTS</b>HLA-matched pairs had higher overall survival (OS) than HLA-mismatched pairs (79.83% vs 73.15%), but there was no statistically significant differences (P > 0.05). HLA mismatch for a single allele plus a single antigen was a significantly risk factor for OS, disease free survival (DFS) and transplant-related mortality (TRM). The OS from high to low in different diseases were thalassemia, AA, CML, MDS, AML, NHL, and ALL. OS of HLA locus mismatch were DRB1 (94.4%), DQB1 (83.3%), B (75%), A (74.4%) and C (71.4%), respectively. OS of single allele mismatch at HLA locus from high to low were DRB1, C, A, B and DQB1.HLA-A, B, C locus mismatch were statistically significantly associated with lower OS and grade II-IV acute GVHD compared with HLA-matched pairs (P < 0.05). The donor-recipient pairs with HLA-B*15:01/B*15:05, DRB1*12:01/DRB1*12:02, C*04:01/C*03:04, DQB1*03:02/DQB1*03:03 alleles mismatch were given priority. But the donor-recipient pairs with HLA-B*39:01/B*39:05, C*15:02/C*14:02, C*08:01/C*03:04, C*07:02/C*15:02 alleles mismatch were risk factors for influence of OS and aGVHD.</p><p><b>CONCLUSION</b>The high resolution typing for HLA-A, B, C, DRB1, DQB1 can be identified nonpermissive mismatch, which is beneficial for the selection of a suitable donor improves survival on unrelated donor HSCT.</p>

Construction of has-miR-335 lentiviral vector and verification of the target gene of miR-335 / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a lentiviral vector of miR-335 gene and verify the target gene of miR-335.</p><p><b>METHODS</b>The precursor sequence of miR-335 gene was amplified from the genomic DNA by PCR and cloned into the lentiviral vector PLVTHM labeled with GFP. Real-time quantitative RT-PCR was used to detect miR-335 and RASA1 expression in different colorectal cancer cell lines. A recombinant vector psiCHECK-2-RASA1 containing RASA1 3'UTR was constructed followed by site-directed mutagenesis of RASA1 3'UTR to establish the vector psiCHECK-2-RASA1-Mut. Co-transfection of hsa-mir-335 or a NC with these recombined vectors in HEK293A and SW480 cells was performed, and dual-luciferase reporter assay was utilized to examine the changes in luciferase activities. The recombinant PLVTHM-miR335 plasmid was packaged into mature lentivirus by 293FT cells and used to infect SW620 cells. Flow cytometry was employed for sorting the GFP+ cells. The expression of miR-335 and RASA1 were determined by qRT-PCR, and Western blotting was used to detect the expression of RASA1 protein in SW620 cell lines.</p><p><b>RESULTS</b>The recombinant lentiviral vector PLVTHM-miR335, psiCHECK-2-RASA1 and the mutation expression vector psiCHECK-2-RASA1-Mut were successfully constructed. Dual-luciferase reporter assay showed that miR-335 decreased luciferase activity in cells co-transfected with psiCHECK-2-RASA1. The expression of miR-335 in SW620 cells infected with the lentivirus PLVTHM-miR335 was significantly increased, but the expression of RASA1 showed only slight changes. Overexpression of miR-335 suppressed the expression of RASA1 protein in SW620 cells.</p><p><b>CONCLUSION</b>We have successfully constructed the lentiviral vector containing mir-335 gene and a SW620 cell line with miR-335 overexpression. MiR-335 can suppress RASA1 gene expression by targeting the specific sequence of RASA1 3'UTR.</p>

Long-term culture and identification of CD133⁺ hematopoietic progenitor cells from human umbilical cord blood / 南方医科大学学报

<p><b>OBJECTIVE</b>To isolate CD133(+) hematopoietic progenitor cells from human umbilical cord blood and optimize the culture condition for maintaining their stem cell characteristics.</p><p><b>METHODS</b>CD133(+) hematopoietic progenitor cells were isolated from human umbilical cord blood using magnetic cell sorting system, and the cells were detected by flow cytometry. Four methods were used for culturing cells. After 8 weeks' culture, cytomorphology, flow cytometry, immunocytochemistry and immunofluorescence assay were used to identify the characteristics of the stem cells.</p><p><b>RESULTS</b>Over 80% of CD133(+) hematopoietic progenitor cells were isolated from human umbilical cord blood using magnetic cell sorting system. The cells were effectively expanded using optimized serum-free medium after 8 weeks of cell culture, whereas the cells in other media differentiated into adherent cells in a poor state.</p><p><b>CONCLUSION</b>The optimized serum-free medium allows effective expansion of CD133(+) hematopoietic progenitor cells that maintain stem cell characteristics after a long-term culture.</p>

Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with peripheral T cell lymphomas: a single centre report / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy. The place for high-dose chemotherapy and autologous stem cell transplantation (ASCT) in these patients is still not clear. In this study, we presented the outcomes of PTCL patients followed these treatments in our centre.</p><p><b>METHODS</b>We retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010.</p><p><b>RESULTS</b>The 3-year overall survival (OS) of 61.9% and 3-year progression free survival (PFS) of 35.7% were observed in the 39 patient. Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further analysis revealed that patients with elevated lactate dehydrogenase, at least 2 international prognostic index (IPI) points, and extranodal involvement had a poorer outcome compared with the control group.</p><p><b>CONCLUSION</b>These findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.</p>

Selection and identification of specific-binding peptides for cancer stem cell surface marker CD133 / 南方医科大学学报

<p><b>OBJECTIVE</b>To select the peptides that specifically bind human cancer stem cell surface marker CD133 from the Ph.D.-7>(TM) phage peptide library.</p><p><b>METHODS</b>With a biotinylated extracellular fragment of human cancer stem cell surface marker CD133 as the target protein, the CD133 high-affinity peptides were screened from the phage peptide library by liquid phase panning. The clones with high-binding force with human CD133 were then identified by sandwich ELISA and their single-stranded DNA was extracted to test the specificity by competitive ELISA. The amino acid sequences of the selected peptides derived from the phage DNA sequences were synthesized after sequence alignment analysis, and their capacity of binding with colorectal carcinoma cells was assessed by immunofluorescence technique.</p><p><b>RESULTS</b>After 4 rounds of liquid phase selection, the phages capable of specific binding with human CD133 were effectively enriched, with an enrichment ratio of 388 times compared to that at the fourth and first rounds. Thirteen out of the 20 clones from the fourth round of panning were identified as positive clones, among which 11 had identical amino acid sequence of TISWPPR, and 2 had the sequence of STTKLAL, and the former sequence showed a stronger binding specificity to CD133.</p><p><b>CONCLUSION</b>We have successfully obtained a peptide that specifically binds human CD133 from the Ph.D.-7(TM) phage peptide library, demonstrating the feasibility of screening small molecule high-affinity polypeptides from phage peptide library by liquid-phase panning.</p>

Clinical study of imatinib for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and therapeutic outcome of imatinib combined with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia chromosome positive acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Thirty patients from Jan 2006 to Mar 2009 were enrolled in this study. All patients received CDOLP induction chemotherapy regimen. Sixteen patients insensitive to chemotherapy were given imatinib simultaneously. Eleven of 30 patients underwent HSCT. The other 19 cases received consolidation therapy including HD-Ara-C, HD-MTX and HD-CTX. Maintenance therapy regimens were VP combined with imatinib.</p><p><b>RESULTS</b>The white blood cell (WBC) count in 17 patients was higher than 30 x 10(9)/L. Of 30 patients, 29 were B cell phenotype and 1 T cell phenotype, 24 had additional chromosomal abnormalities. The overall complete remission (CR) rate was 96.7%. The median CR duration was 9 (2 - 20) months. The 1-year and 3-year overall survival (OS) rates were (64.7 +/- 9.8)% and (30.0 +/- 12.4)%, and the event free survival (EFS) rates were (28.8 +/- 9.5)% and (19.2 +/- 10.1)%, respectively. The bcr-abl transcripts in 13 of 30 patients were continuous negative. The OS rate in patients with negative bcr-abl transcripts was higher than that with positive bcr-abl (70.7% vs 61.3%) (P = 0.189). The EFS rate of patients with continuous negative bcr-abl transcripts was significantly higher than that of patients with continuous positive bcr-abl transcripts (P = 0.01). The median overall survival duration of higher WBC count group and normal WBC count group were 10 (4 - 18) and 29(5 - 36) months, respectively. The patients of higher WBC count had lower OS and EFS rates than that of normal WBC count (46.9% and 15.5% vs 83.5% and 50.8%, respectively) (P = 0.003 and 0.009, respectively).</p><p><b>CONCLUSION</b>Imatinib can significantly improve molecular CR rate and CR duration for Ph(+) ALL patients. Imatinib combined with allo-HSCT is expectable to improve the curative ratio of these patients.</p>

Clinical study of allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and toxicity of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory acute lymphocytic leukemia (ALL).</p><p><b>METHODS</b>Forty-seven patients with relapsed/refractory ALL received allo-HSCT, which containing 19/47 from HLA-identical sibling donors (sib-HSCT), 18/47 from HLA-identical unrelated donors (URD-HSCT) and 10/47 from haplo-identical donors (Hi-HSCT). Conditioning regimens included "TBI plus Cyclophosphamide (Cy) (42/ 47)" or "busulfan (Bu) plus Cy (5/47)". Cyclosporine (CsA) combined with a short-course Methotrexate (MTX) were used for graft versus host disease (GVHD) prophylaxis. In addition, patients receiving URD-HSCT or Hi-HSCT were given mycophenolate mofetil (MMF) and anti-thymocyte immunoglobulin (ATG). Patients with molecular or cytogenetic relapse tendency on minimal residual disease (MRD) monitoring received donor lymphocyte infusion (DLI).</p><p><b>RESULTS</b>All patients tolerated the therapy well except for mucositis. Renal dysfunction occurred in 2 patients on CsA therapy. Epilepsy occurred in 1 patient, fatal infectious complications in 9 (including 3 interstitial pneumonia), grade III-IV acute GVHD (aGVHD) in 7, chronic GVHD (cGVHD) in 22 and hemorrhagic cystitis (HC) in 4 patients. Thirteen patients relapsed after transplantation. The median time of hematopoietic reconstitution was + 17 ds. Nineteen patients received DLI, and 6 of them had no disease progression. With a median follow-up duration of 43 (10-77) months, the estimated 5-year overall survival (OS) and disease free survival (DFS) rates were 49.65% and 46.55%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT is an effective therapy for relapsed/refractory ALL. Relapse after transplantation, fatal infection, and severe acute GVHD are the main causes for failure. DLI might decrease the relapse rate after transplantation.</p>

Relationship between CMV reactivation and KIR haplotype/HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between CMV reactivation and KIR haplotype or HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>From January 2003 to December 2008 the HLA-Cw/KIR genotype of 48 patient-donor pairs were determined by polymerase chain reaction with sequence specific primers (PCR-SSP) and sequence specific nucleotide (PCR-SSOP). Posttransplant CMV reactivation was performed by immune histochemically assay.</p><p><b>RESULTS</b>Of 48 patients, 15 were transplanted from unrelated donors with an antigen mismatch for HLA Cw and 33 patient-donor pairs were matched for HLA-Cw. The CMV reaction rate was 66.7% for HLA-Cw mismatch group and 48.5% for HLA-Cw match group (chi(2) = 1.39, P = 0.2375). Thirty-seven donor-patients pairs belonged to group C1 and 11 to group C2, and CMV reaction rate was 64.9% in group C1 and 18.2% in group C2 (chi(2) = 18.13, P < 0.0001). Twenty-six patients received graft from KIR haplotype A (group A donor) and 22 from KIR haplotype B donors (group B donor) and CMV reaction rate was 57.7% in group A donor and 50.0% in group B donor (chi(2) = 0.28, P = 0.5941). The number of donor activating KIRs (aKIRs) was less than that of recipient aKIRs in 34 patient-donor pairs in which the CMV reaction rate was 70.6%, and the number of donor aKIRs was more than that of recipient aKIRs in 14 patient-donor pairs in which the CMV reactivation was 14.3%. There was a significan difference between the two group (chi(2) = 12.44, P = 0.0004).</p><p><b>CONCLUSION</b>KIR and HLA-Cw genotypes influence the rate of CMV reactivation following non-T cell deleted unrelated donor hematopoietic cell transplantation.</p>

A comparison of clinical outcomes between unrelated donor and HLA-haploidentical donor hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the clinical outcomes between unrelated donor hematopoietic stem cell transplantation (URD-HSCT) and HLA-haploidentical (Hi)-HSCT.</p><p><b>METHODS</b>Twenty-five patients with hematologic malignancies received URD-HSCT and thirty patients received Hi-HSCT. The conditioning regimen consisted of modified BUCY or modified total body irradiation (TBI) plus CY. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of cyclosporin ( CsA), short-term methotrexate (MTX), mycophenolate mofetil (MMF), or the combination of CsA, MTX and MMF plus antithymocyte globulin (ATG) or antilymphocyte globulin (ALG), or the combination of CsA, MTX, MMF, ATG/ ALG and CD25 monoclonal antibody.</p><p><b>RESULTS</b>All patients in the URD-HSCT group and 29 patients in the Hi-HSCT group were engrafted successfully. The median follow-up duration was 7 (2 -59) months for URD-HSCT group and 7.3 (1 - 35) months for Hi-HSCT group. The 3-year probabilities of disease-free survival (DFS) for URD-HSCT and Hi-HSCT group were (54.1 +/- 11.9)% and (43.1 +/- 9.1)%, respectively (P =0.13). Grade III - IV aGVHD occurred in 10 patients in URD-HSCT group and 11 in Hi-HSCT group (the cumulative incidence 40.0% vs 37.9%, P > 0.05), respectively. Ten patients (40.0%) died of transplantation-related mortality (TRM) in URD-HSCT group and 17 (56.7%) in Hi-HSCT group (P >0. 5). Two patients relapsed in each group (the rate of relapse 8.0% vs 6.0%, P >0.05). The primary causes of death included severe aGVHD with infection,severe pulmonary infection and relapse.</p><p><b>CONCLUSION</b>Both URD-HSCT and Hi-HSCT are effective and curable treatment for refractory or high-risk hematologic malignancies. The optimal donor should be chose individually. The severe aGVHD and consequent infection are still the main cause of TRM.</p>

Preliminary study of the effect of HLA-Cw on haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of HLA-Cw on haploidentical hematopoietic stem cell transplantation (HHSCT) without T-cell depletion.</p><p><b>METHODS</b>HLA-Cw were detected with PCR-SSP, the clinical data of 21 cases of haploidentical hematopoietic stem cell transplantation, including 8 standard risk and 13 high risk cases from July 2002 to March 2006 were summarized, and the effect of HLA-Cw in HHSCT was analyzed.</p><p><b>RESULTS</b>Twenty patients achieved sustained, full-donor-type engraftment. The HLA-Cw matched and mismatched groups attained neutrophil recovery at a median of 12 days and 13 days, and platelet recovery to more than 20 x 10(9)/L at a median of 20 days and 23 days respectively (P > 0.05). The cumulative incidences of grades II-IV acute GVHD were 76.9% in HLA-Cw matched group and 14.3% in the mismatched group(P < 0.05). The incidences of chronic GVHD were 85.7% in HLA-Cw matched group and 57.1% in the mismatched group(P > 0.05). The 28 months disease-free survival probabilities were 49.0% in HLA-Cw matched group, and 85.7% in the mismatched group (P > 0.05). The Karnofsky score of survival patients was over 90%.</p><p><b>CONCLUSION</b>HLA-Cw mismatched in donor and recipient of HHSCT is beneficial for reducing II-IV aGVHD, and being in favor of long term survival.</p>

Role of CD28/CTLA-4 co-stimulators in immune pathophysiology of aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the possible role of CD28/CTLA-4 co-stimulators in immune pathophysiology of acquired aplastic anemia(AA).</p><p><b>METHODS</b>By FACS, the percentages of CD28, CTLA-4 expressing CD3+ CD4+ T cells and the level of Th1, Th2 in bone marrow were detected in 23 AA patients at active phase, 10 at recovery phase and 15 normal controls. The relationship between the co-stimulators, Th1, Th2, and absolute neutrophil counts (ANC) was evaluated.</p><p><b>RESULTS</b>(1) The percentage of CD28 and CTLA-4 expressing CD3+ CD4+ T cells in bone marrow, and CD28+/CTLA-4+ ratios were (31.40 +/- 10.83)%, (2.45 +/- 1.30)% , and 17.02 +/- 13.44 in normal controls respectively, (39.84 +/- 10.89)%, (1.43 +/- 0.67)%, and 43.04 +/- 37.61 in AA at active phase, respectively, (22 +/- 9.08)%, (3.46 +/- 2.26)%, and 10.49 +/- 7.8 in AA at recovery phase, respectively. The percentage of CD28 and CD28+/CTLA-4+ ratio were significantly higher, while CTLA-4 were lower in active phase AA patients than in normal controls (P < 0.05). These values in recovery phase AA were comparable to those in normal controls. (The Th1, Th2, and Th1/Th2 in bone marrow were (4.21 +/- 2.11)%, (1.99 +/- 1.27)%, and 2.46 +/- 1.28 in normal controls respectively, (11.13 +/- 4. 96)%, (2.46 +/- 1.65)%, and 5.20 +/- 1.98 in active phase AA and (5.39 +/- 4.2)9%, (2.53 +/- 2.41)%, and 2.87 +/- 1.43 in recovery phase AA, respectively. The percentage of Th1 and Th1/Th2 ratio were significantly higher in AA patients at active phase than in normal controls (P < 0.05). (3) The CD28+/CTLA-4+ ratio was positively related to the Th1+ /Th2+ ratio (P < 0.05). ANC was negatively related to CD3+ CD4+ CD28+ T cells (P < 0.01), and positively to CD3 + CD4 ' CTLA-4' T cells (P < 0.01) respectively.</p><p><b>CONCLUSION</b>(1) The expression of CD28 was increased while CTLA-4 decreased on the membranes of CD3+ CD4+ T cells in bone marrow of AA patients. (2) The abnormal expression of CD28 costimulator promoted the shift of immune balance to Thl type. (3) The unbalance of CD28+ / CTLA-4+ is important for the immune pathophysiology of AA.</p>

Pulmonary disease caused by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation--a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To report a case with pulmonary disease caused by nontuberculous mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a literature review.</p><p><b>METHODS</b>Case report and literature review.</p><p><b>RESULTS</b>A patient with acute non-lymphocytic leukemia was treated by allo-HSCT. Her NTM lung disease developed after HSCT was successfully treated with a 3 antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10 months.</p><p><b>CONCLUSION</b>NTM infections are infrequent in allo-HSCT recipients and have a good clinical prognosis if correctly treated.</p>