Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group (P = 0.03 and P = 0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%-86.7%) and 58.4% (95% CI: 41.9%-81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%-35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%-38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.
Adult ; Busulfan/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Graft vs Host Disease/prevention & control* ; Hematopoietic Stem Cell Transplantation ; Humans ; Neoplasms ; Peripheral Blood Stem Cell Transplantation ; Pharmaceutical Preparations ; Prospective Studies ; Transplantation Conditioning ; Vidarabine/analogs & derivatives*

OBJECTIVE: To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL). METHODS: A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined. RESULTS: The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05). CONCLUSION Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.
Apoptosis ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; MicroRNAs ; Phosphatidylinositol 3-Kinases ; Vidarabine ; analogs & derivatives ; genetics ; therapeutic use

OBJECTIVETo explore the clinical efficacy and safety of rituximab combined with fludarabine and cyclophosphamide for the treatment of the chronic lymphocytic leukemia (CLL).

METHODSForty cases of CLL patients treated in our hospital from March 2010 to March 2014 years were selected and divided into the observation group (20 cases) and control group (20 cases) by random number table method. The patients in control group were treated with CHOP chemotherapy, the patients in observation group were treated with rituximab combined with fludarabine, cyclophosphamide treatment. The therapeutic efficacy of patients in 2 groups was analyzed according to the peripheral hemogram indexes, symptom and sign disappeared time as well as adverse reaction incidence.

RESULTSthe remission rate in observation group was 90.00%, which was significantly higher than that in control group (70.00%) (P < 0.05); the peripheral hemogram indexes in 2 groups before treatment showed no significant difference (P > 0.05), and were significantly improved after treatment, but the white blood cell count and lymphocyte absolute number were significantly lower in observation group as compared to the control group (P < 0.05); symptom and sign disappeared time in observation group were significantly shorter as compared with the control group (P < 0.05); adverse reaction incidence in obseovation group was significantly lower as compared with control group (P < 0.05).

CONCLUSIONapplication of rituximab combined with fludarabine and cyclophosphamide in the treatment of CLL shows the higher curative effect, can effectively improve the symptoms and reduce the incidence of adverse reactions. It is worthy to be popularized.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Doxorubicin ; therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Prednisone ; therapeutic use ; Rituximab ; administration & dosage ; therapeutic use ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Vincristine ; therapeutic use

OBJECTIVETo evaluate the efficacy of FLAG regimen for treating patients with refractory/relaspse AML and their progonistic factors.

METHODSThe 38 patients with median age 40.5 (range 13-69) were treated with FLAG regimen from July 2006 to July 2013 in hospital. According to disease status, all the patiens were divided into 4 different groups: early relapse group (3 patients), late relapse group (12 patients), first induction failure group (16 patients) and second induction failure group (7 patients); meanwhile, based on risk status, all above-mentioned patients were stratified into better (8 patients), intermediate (26 patients) and poor (4 patients) groups, respectively.

RESULTSTwenty two cases achieved complete remission, 5 cases achieved partial remission among 38 patients. The complete remission (CR) rate was 57.9% and the overall response (OR) rate was 71.7%. The CR rate was higher in first induction failure group (12/16, 75%) than that in second induction failure group (3/7, 42.9%) and late relapse group (6/12, 50%). In better group and intermediate group, the CR rates (5/8, 62.5%; 16/26, 61.5%) were higher than that in poor group (1/4, 25%). The risk status was associated with the CR rate (P = 0.03) [OR = 25.9(95% CI 1.2-545.4)]. The intermediate risk was favorable factor to CR. Out of 22 patients with CR, 12 patients received allogenetic hematopoietic stem cell transplantation (allo-HSCT) and 10 patients received large dose of cytarabine or other regimens as consolidation treatments, 6 patients who accepted allo-HSCT are still alive. The overall survival (OS) was 25 months. The univariate analyses showed that the response to FLAG was accociated with OS [HR = 0.246, CR vs NR (95% CI 0.07-0.79) P = 0.03]. The 2-year cumulative survial rates in CR group and PR group were 62% and 48%, respectively. The 18- month cumulative survival rate was 73% in better group, 52% in intermediate group, 36% in poor group (P = 0.17); and 65% in first induction failure group and 32% in second induction failure group (P = 0.19).

CONCLUSIONThe efficacy of FLAG regimen has been confirmed to be effective for patients with refractory and relapse AML. The patients who achieved remission could acquire benefit from following HSCT or other consolidation chemotherapy, and their survials could be improved.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chronic Disease ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Middle Aged ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance.

METHODSA total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used.

RESULTSAll the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%).

CONCLUSIONThese data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

Antilymphocyte Serum ; therapeutic use ; Busulfan ; therapeutic use ; Cyclosporine ; therapeutic use ; Graft vs Host Disease ; prevention & control ; HLA Antigens ; genetics ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Leukemia ; therapy ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; Vidarabine ; analogs & derivatives ; therapeutic use

OBJECTIVETo analyze the treatment outcome of a consecutive series of 100 leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical data of leukemia patients received allo-HSCT were analyzed retrospectively, the therapeutic efficacy was summarized. 100 evaluable cases of leukemia included 47 cases of AML, 33 cases of ALL, 2 cases of AL (biphenotypic), 16 CML and 2 CMML. Before transplantation, 76 cases were in first complete remission, 9 cases in second or greater complete remission and 15 cases in non-remission or relapse. All the patients received peripheral blood hematopoietic stem cell transplantation (PBHSCT). The conditioning regimen of human leukocyte antigen (HLA)-matched allo-HSCT group was modified BuCy, but in HLA-mismatched group Fludarabine and anti-human thymocyte globulin (ATG) was added. CsA+MTX regimen was used for prophylaxis of graft-versus-host disease (GVHD) in HLA-identical allo-HSCT, while additional MMF was added in HLA-mismatched group. The average time of follow-up was 13 months.

RESULTSAt the last follow-up, 66.0% (66/100) patients survived, 53.0% (53/100) patients survived without leukemia, 28.0% (28/100) patients relapsed and 34.0% (34/100) patients died, 44.1% patients of them died from infectious pulmonary complications. During transplantation, 65.0% of the patients were suffered from lung infection. The overall survival (OS) and disease-free survival (DFS) of all cases was 60.9% and 48.8%, respectively. The recurrence rate was significantly higher in non-remission (66.7%) than in CR (21.2%) patients (P < 0.05). The cumulative incidence of GVHD in HLA-mismatched transplantation was 60.8%, which was significantly higher than that of HLA-matched transplantation (38.8%) (P < 0.05).

CONCLUSIONAllo-HSCT can cure a significant proportion of leukemia patients, especially for those in CR status. Since the incidence of infectious pulmonary complications after allo-HSCT is still high, much more attention should be paid to it. The comprehensive prognosis of HLA-matched transplantation is better than the HLA-mis-matched transplantation.

Antilymphocyte Serum ; therapeutic use ; Disease-Free Survival ; Graft vs Host Disease ; prevention & control ; HLA Antigens ; genetics ; Humans ; Incidence ; Leukemia ; therapy ; Peripheral Blood Stem Cell Transplantation ; Recurrence ; Retrospective Studies ; Transplantation Conditioning ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use

OBJECTIVETo evaluate the outcomes of allogeneic hematopoietic stem cell transplantation（allo-HSCT）for paroxysmal nocturnal haemoglobinuria（PNH）and aplastic anemia（AA）- PNH syndrome.

METHODSThe clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT（1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation）, 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow: 13 patients received modified BU/CY- based regimens, 5 non- myeloablative regimens ［fludarabine （Flu） + antithymocyte globulin（ATG）+ cyclophosphamide（CY）or busulfan（BU）］. Prophylaxis for graft- versushost disease（GVHD）: the patients with HLA-identical sibling donor received cyclosporine（CsA）plus short-term methotrexate（MTX）, the patients with HLA -haploidentical donor or HLA-identical unrelated donor received CsA or tacrolimus（FK506）+ mycophenolate mofetil（MMF）+ short- term methotrexate （MTX）.

RESULTSAll patients were engrafted successfully（1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation）. The median days of neutrophils（ANC）above 0.5 × 109/L and platelets （PLT） more than 20 × 10⁹/L were 11（10- 26）days and 15（11- 120）days, respectively. Three patients（17.6%）developed acute GVHD（aGVHD）, 2 for grade Ⅱ aGVHD, 1 for grade Ⅳ aGVHD. Of 16 patients, 2 occurred limited chronic GVHD（cGVHD）. After a median follow-up of 14.6（2.0-86.7）months, 3 patients（17.6%）died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplant- associated thrombotic microangiopathy. The 5- year estimated disease free survival was（80.5 ± 10.2）%. No patient relapsed.

CONCLUSIONAllo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.

Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Busulfan ; Cyclophosphamide ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal ; therapy ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies ; Siblings ; Tacrolimus ; Transplantation Conditioning ; Treatment Outcome ; Unrelated Donors ; Vidarabine ; analogs & derivatives

OBJECTIVETo investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu).

METHODSA total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively.

RESULTSAll patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS.

CONCLUSIONBu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

Busulfan ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Recurrence ; Remission Induction ; Retrospective Studies ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; Vidarabine ; analogs & derivatives

Animals ; Bone Marrow Transplantation ; Busulfan ; Disease Models, Animal ; Drug Combinations ; Graft vs Host Disease ; Mice ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives

OBJECTIVEThis study was aimed to investigate the morphological, immunophenotype, cytogenetic characteristics, clinical and therapy features in one elderly patient with chronic lymphocytic leukemia (CLL) combined with invasive aspergillose infection(IAI).

METHODSThe morphological features of bone marrow cells from patient were observed by light microscope, the immunophenotype were detected by flow cytometry, the cytogenetic characteristics were assayed by conventional chromosomal analysis and fluorescence in situ hybridization (FISH).

RESULTSat onset of disease, the patient was diagnosed as B-CLL, Rai stage is II. He was treated with a course of RF(fludarabine 50 mg×5, rituximab 600 mg×5) chemotherapy, and achived complete remission (CR) lasting for five years, then the patient was treated with multiple courses of chemotherapy and maintained at a steady state of disease. After the last chemotherapy, this patient developed a fever, his temperature fluctuated at 37.2-38.7°C, the lung CT showed the presence of massive shadow, repeated 1-3-β-D-glucan test was positive,and he was considered as invasive aspergillosis infection, voriconazole was intravenously injected him for 2 months, his lung CT showed better efficacy. However, the leukemia continued progress, his hemogram was extremely low, invasive aspergillosis infection relapsed,voriconazole treatment was poor effect,ultimately this patient died of the rapid progress of leukemia and multiple organ invasive aspergillosis. Autopsy showed chronic lymphocytic leukemia with multiple metastases and multiple organ invasive aspergillosis.

CONCLUSIONinvasive aspergillosis is a serious complication for CLL patients,once occurs, the prognosis is poor,so early diagnosis and prophylactic antifungal therapy may reduce fungal infection complication.

Aged ; Antibodies, Monoclonal, Murine-Derived ; Antifungal Agents ; Antineoplastic Combined Chemotherapy Protocols ; Aspergillosis ; Flow Cytometry ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Remission Induction ; Rituximab ; Vidarabine ; analogs & derivatives