Objective To summarize the clinical features of graft failure (GF)after non-T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HCT), and to investigate the causes and treatment. Methods A retrospective analysis was carried out on 174 patientswho accepted the non-T-cell depleted Haplo-HCT from Jan 2012 to Dec 2013. The patients′ donor specific anti human leukocyte antigen antibodies (DSA) from the peripheral blood serum were detected and those DSA positive patients were treated by immunoglobulin or plasma exchange before transplatation. Results A total of three patients with acute myeloid leukemia got GF, the incidence rate was 1.72%. The patient with primary GF was given a secondHaplo-HCT, but did not get implanted with leukemia remission and three lineages persistently low , he was died of pulmonary infection eight monthes after the second transplant. One of the secondary GF patients was given peripheral blood mononuclear cells(PBMNCs) mobilized by granulocyte colony stimulating factor (G-CSF) from the donor, and got full donor chimerism on day 16 after infusion. The disease-free survival has been for 18 months. The other case was found that DSA was positive, the mean fluorescence intensity (MFI) value was 15000, then Rituximab and PBMNCs mobilized by G-CSF were administrated successively. On day 14 after infusion the partient got full donor chimerism , and MFI turned negative. The patient has been disease-free survival for 41 months. Conclusion Graft failure is a rare but fatal complication after non-T-cell depletedHaplo-HCT, Rituximab followed by PBMNCs are effective measures for DSA related GF, as were worthy of further study.

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions: The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.
Cardiovascular Agents ; Coronary Artery Disease ; Drug-Eluting Stents ; Humans ; Percutaneous Coronary Intervention ; Prognosis ; Prospective Studies ; Risk Assessment ; Risk Factors ; Sirolimus ; Treatment Outcome

OBJECTIVETo screen the high risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) respectively, then to compare the contribution of each risk factor to relapse and investigate the relevant mechanisms.

METHODSA retrospective study from single center involved in 262 evaluable cases of leukemia received allo-HSCT over the past 8 years, of them 69 cases with ALL, 90 AML (except APL) and 103 CML. Cox proportional hazard regression model was used for univariate and multivariate analysis to screen the high risk factors.

RESULTSThe risk factors significantly affecting relapse in ALL included: Cytogenetic risk classification, the cycles of initial induction chemotherapy; AML: Cytogenetic risk classification, minimal residual disease (MRD) level before transplant, reconstitution of WBC, and CD4(+)/CD8(+) lymphocyte ratio in the graft; CML: disease stage before transplant.

CONCLUSIONSThe relapse risk after HSCT of ALL mainly depends on the grade of malignancies, and the relapse risk of AML is closely related to the course of transplant. Chronic phase of CML favors a good prognosis after HSCT. Cytogenetic risk classification is the most relevant predictor of relapse after HSCT.

Adolescent ; Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; pathology ; surgery ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; Transplantation, Homologous ; Young Adult

Objective To explore the eff cacy and safety of 6-month and 12-month dual antiplatelet therapy(DAPT)after implantation of biodegradable polymer-drug eluting stents(BP-DES) in elderly patients. Methods This study was a subgroup analysis of the I-LOVE-IT 2 trial, which was a prospectively randomized study enrolling 2737 patients receiving either a BP-SES or a DP-SES in a 2:1 ratio. This studied further divided the patients who were randomized to the BP-SES group,whose age ≥ 65 year old, in a 1:1 ratio to receive a 6-month DAPT (n=319) or 12-month DAPT (n=308)randomly before the index PCI. The primary end point of this study was 12-month target lesion failure (FhF, including cardiac death,target vessel myocardial infarction and clinically indicated target lesion revascularization)and the secondary end points was 12-month net adverse clinical and cerebral events (including all-cause death, all myocardial infarction, stroke and all bleeding). Results Rates of TLF at 12 months were 7.1% in the 6-month DAPT group and 7.2% in the 12-month DAPT group (P=0.980). No diff erences were observed in the occurrence of events in the secondary endpoint at 12 months follow-up between the 6-month DAPT group and 12-months DAPT group(14.1% versus 13.0%, P=0.726). There were no signifi cant diff erences in stent thrombosis or bleeding complications between the 2 groups. Conclusions This study shorted that 6-month DAPT did not increase the risk of TLF at 12 months after implantation of DES in elderly patients compared with 12-month DAPT. Elderly patients are at high risk of bleeding and ischemic events and study show that 6-month DAPT would be adequate. These results need to be confi rmed with trials of scale in the future.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; therapy ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Retrospective Studies ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cells (MSCs) infusion in patients with steroid-resistant severe acute graft-versus-host disease (aGVHD).

METHODSA total of 19 patients with steroid-resistant severe aGVHD received MSCs infusion treatment. The treatment response, transplantation-related mortality, events associated with infusion and relapse rate were analyzed.

RESULTSTwo patients with grade II, 5 patients with grade III and 12 patients with grade IV aGVHD received a total of 58 infusions of MSCs. The mean total dose of MSCs was 2.13 (range 0.60 - 7.20)×10(6) cells per kg bodyweight. Seven patients received one infusion, 2 patients received two infusions, and 10 patients received three or more infusions. Eleven patients had a complete response and 4 had a partial response and 4 had no response. No patients had side-effects during or immediately after infusions, and no MSCs related tumorigenesis was detected to date. Eleven patients survived and 8 died, 4 for aGVHD, 1 for infection and 2 for aGVHD with concomitant infection and 1 for underlying leukemia relapse. The cell viability of freshly prepared MSCs is 93% (92% - 95%) by trypan blue staining. The cell viability of programmatically frozen and thawed MSCs is 72% (70% - 74%).

CONCLUSIONInfusion of umbilical cord-derived MSCs expanded in vitro is an effective therapy for patients with steroid-resistant severe aGVHD without negative impact on relapse. Freshly prepared MSCs are superior to frozen and thawed cells in terms of cell viability.

Adolescent ; Adult ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; etiology ; surgery ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Middle Aged ; Steroids ; pharmacology ; Survival Rate ; Umbilical Cord ; cytology ; Young Adult

OBJECTIVETo investigate the clinical and biological characteristics and prognosis of mixed phenotype acute leukemia (MPAL).

METHODSThirty two patients were diagnosed as MPAL by bone marrow examination, immunophenotyping, cytogenetic and molecular assay and were treated with combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia. Two cases were received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

RESULTS(1) The incidence of MPAL in acute leukemias was 2.6%. There were 16 cases (50.0%) of mixed myeloid and B-lymphoid (M/B), 14(43.8%) myeloid and T-lymphoid (M/T), one each (3.1%) of trilineage (M/B/T) and B- and T-lymphoid (B/T) phenotype. (2) The positive rates of CD34 and HLA-DR were 87.5% and 62.5%, respectively. (3) Abnormal karyotypes were detected in 70.0% of 30 MPAL patients, which were structural and numerical abnormalities including t(9;22), 11q23 and complex karyotypes. (4) The total complete remission (CR) rate was 75.0% and the overall survival (OS) and disease-free survival (DFS) at 2 years were 14.8% and 14.2% respectively. The CR rates for M/B and M/T cases were 75.0% and 71.4% respectively. No statistical difference was observed in OS and DFS between M/B and M/T cases.

CONCLUSIONSMPAL is a rare type of acute leukemia with a high heterogeneity. The unfavorable indicators of MPAL may be factors such as abnormal karyotypes, high expression of CD34 and extramedullary infiltration. Combined regimens and more intensive therapy including allo-HSCT might contribute to improving survival.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Immunophenotyping ; Karyotype ; Leukemia, Biphenotypic, Acute ; classification ; genetics ; immunology ; Leukemia, Myeloid, Acute ; genetics ; immunology ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; Prognosis ; Young Adult

OBJECTIVETo explore the possible role of CD28/CTLA-4 co-stimulators in immune pathophysiology of acquired aplastic anemia(AA).

METHODSBy 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.

RESULTS(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.

CONCLUSION(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.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; immunology ; metabolism ; Antigens, CD ; immunology ; metabolism ; CD28 Antigens ; immunology ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CTLA-4 Antigen ; Child ; Female ; Humans ; Male ; Middle Aged ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor (CAG) regimen for refractory biphenotypic acute leukemia (BAL).

METHODSWe treated 5 refractory BAL patients by CAG regimen (10 mg x m(-2) cytosine arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg x m(-2) aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200 microg x m(-2) x d(-1) granulocyte colony-stimulating factor subcutaneously) from November 2002 to April 2007. The efficacy of the regimen was evaluated by response rate, and the side effects were also measured.

RESULTSThe complete remission rate was 80%, median duration of absolute neutrophil count < 5.0 x 10(8)/L and platelet count < 2.0 x 10(10)/L was day 13 and day 1, respectively; and the infection rate was low (III-IV infection rate, 20.00%).

CONCLUSIONCAG regimen as remission induction chemotherapy for BAL patients is effective with a high remission rate and low toxicity.

Aclarubicin ; administration & dosage ; adverse effects ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Cytarabine ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; adverse effects ; Humans ; Leukemia, Biphenotypic, Acute ; drug therapy ; Male ; Remission Induction ; Treatment Outcome ; Young Adult

This study was aimed to analyze the survival status of patients with diffuse large B-cell lymphoma (DLBCL) and to investigate the influence of autologous hematopoietic stem cell transplantation (auto-HSCT), different pathological types, International Prognosis Idex (IPI) on prognosis. One hundred and sixteen cases of DLBCL were analyzed retrospectively. The treatment efficacy of R-CHOP alone and R-CHOP combined with auto-HSCT as well as the influence of different immunopathologic types, IPI, hypersensitive C-reactive protein (HSCRP), α-hydroxybutyric acid deaminase (HBDH) on the prognosis of DLBCL patients including overall survival (OS) rate, progression-free survival (PFS) rate were analyzed. The results indicated that the 5-year OS for all patients was 72.4%. in which 30 patients with Ann Arbor staging III-IV received auto-HSCT plus R-CHOP. The prognosis of the 30 patients was better than that of 86 cases received R-CHOP chemotherapy alone (5-year OS was 82.5% vs 69.0%, 5-year PFS was 77.1% vs 68.3%) (P < 0.05). The prognosis of patients in germinal center B-cell-like group (GCB group) was better than that of patients in activated B-cell-like group (ABC group). Some clinical features were associated with poor prognosis including OS and PFS, such as age, B symptoms, IPI scores, the level of LDH, HSCRP and HBDH (P < 0.05) in which the level of LDH, age ≥ 60 years and B symptoms were independent prognostic factors in DLBCL patients (P < 0.05). It is concluded that auto-HSCT combined with R-CHOP can improve the long-term survival of DLBCL patients. The prognosis of patients in GCB group is better than that of patients in the ABC group. The clinical features such as age, B symptoms, IPI scores and LDH are associated with prognosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; therapy ; Male ; Middle Aged ; Prednisone ; Prognosis ; Retrospective Studies ; Vincristine ; Young Adult