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Jian-Min Wang,
Wei-Ping Zhang,
Xian-Min Song,
Cao-Bo Feng,
Jian-Min Yang,
Li Chen, Jun Hou,
Hong Zhou,
Xiong Ni,
Lei Gao,
Hui-Ying Qiu,
Hong-Mei Li,
Xiao-Qin Ding
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ABSTRACT: To evaluate the overall efficacy and transplant-related mortality (TRM) of related and unrelated allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT) in chronic myeloid leukemia (CML) patients conditioned with fludarabine-busulfan (FB) reduced intensity regimen.
Forty-four patients received FB (Flud 30 mgxm(-2)xd(-1) x 5 d, BU 4 mgxkg(-1)xd(-1) x 3 d) conditioning followed by allo-PBSCT. Of them, 29 patients were transplanted with related donor and 15 unrelated donor (URD). All patients received mycophenolate mofetil (MMF), CsA and MTX for acute GVHD (aGVHD) prophylaxis. 5 mg/kg rabbit-antithymocyte globulin (ATG-Fresenius) was incorporated in 15 URD recipients.
All patients were successfully engrafted. The median times to ANC above 0.5 x 10(9)/L in related (RG) and unrelated groups (URG) were 13.7 (9 - 18) d and 13.6 (12 - 17) d, and PLT above 20 x 10(9)/L were 15.3 (9 - 20) d and 14.7 (10 - 26) d, respectively. Two patients in RG. 1 in URG developed graft rejection 5 - 8 months after transplantation. One of the two patients in RG received second transplantation and engrafted. The cumulative incidence of aGVHD and cGVHD were 13.8% (4/29) and 46.4% (13/28) in RG, and were 33.3% (5/15) and 57.1% (8/14) in URG respectively. Two patients in RG relapsed after transplantation, and obtained CR again after donor stem cell infusion (DSI). Median time of follow-up was 34.7 (2 - 73) months. Thirty-four patients were alive and 10 died. The main causes of death were IP, GVHD, graft rejection and infection. The 5-year overall survival (OS) probability was 77.0%, and the disease-free-survival (DFS) was 73.9%, of which, 79.0% and 74.1% were in RG, and 73.3% and 73.3% in URG, respectively.
Fludarabine-busulfan based reduced intensity conditioning for allo-PBSCT with either related or unrelated donors is a safe, less toxic and curative approach to CML.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 02/2010; 31(2):77-81.
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ABSTRACT: The response to remission induction in elderly patients with acute myeloid leukemia (AML) remains poor. The purpose of this paper is to evaluate the efficacy and toxicity of a plant alkaloid, homoharringtonine, in combination with cytarabine as an induction therapy for AML in elderly patients (> or =60 years).
Twenty-three patients were treated with the HA regimen consisting of homoharringtonine (2 mg/m2/day for 7 days) and cytarabine (Ara-C, 100 mg/m2/day for 7 days). The overall response rate was 56.5% with complete remission (CR) rate of 39.1% and partial remission of 17.4%. There was no early death in this cohort of patients. The estimated median overall survival (OS) time of all patients was (12.0 +/- 3.0) months. The estimated OS time of the CR patients was 15 months. The estimated one-year OS rate of all patients treated with HA protocol was (49.3 +/- 13.5) %. The estimated one-year OS rate of the CR patients was (62.5 +/- 17.1) %.
HA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate.
Journal of Hematology & Oncology 08/2009; 2:32. · 3.99 Impact Factor
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ABSTRACT: Biphenotypic acute leukemia is a rare disorder that is difficult to diagnose. It displays features of both myeloid and lymphoid lineage. There is still a lack of studies in biphenotypic acute leukemia in a Chinese population. We present here a comprehensive investigation of the clinical and biological characteristics, and outcome of biphenotypic acute leukemia in our hospital in over a seven year period.
We retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and biphenotypic acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in biphenotypic acute leukemia patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period.
Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as biphenotypic acute leukemia. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was T/B lymphoid and one (4.8%) was trilineage differentiation. When compared with acute myeloid leukemia and acute lymphoblastic leukemia, patients with biphenotypic acute leukemia showed significantly higher incidence of CD34 antigen expression, unfavorable karyotypes, and extramedullary infiltration (p<0.05). In this cohort of patients with biphenotypic acute leukemia, t(9;22) was the most common abnormality in chromosome structure. The median disease-free survival and overall survival in biphenotypic acute leukemia patients was five months and ten months, respectively, significantly shorter than those in acute myeloid leukemia and acute lymphoblastic leukemia patients (p<0.05).
The prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse.
Haematologica 06/2009; 94(7):919-27. · 6.42 Impact Factor
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Xiao-qian Xu,
Jian-min Wang,
Shu-qing Lu,
Li Chen,
Jian-min Yang,
Wei-ping Zhang,
Xian-min Song,
Yan-qun Xu,
Sheng-lan Gong, Jun Hou,
Xiong Ni
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ABSTRACT: To investigate the WHO classification, clinical and hematological features and risk group of International Prognostic Scoring System (IPSS) in patients with myelodysplastic syndrome (MDS).
The diagnosis and classification of MDS patients were defined according to the WHO classification. The clinical manifestations, hemogram, bone marrow biopsy and prognosis were retrospectively analyzed.
The median age at diagnosis of MDS was 47 yrs being younger than that in some foreign reports. The frequency of abnormal karyotype was 35.14% and +8 was the most frequent abnormal karyotype in our study. Eleven of 74 patients transformed into leukemia. Univariate analysis showed that age, chromosome abnormality, percentage of bone marrow blast cells and number of cytopenias were significantly related to prognosis. There was a statistical difference in cum survival rate between IPSS subcategories (P < 0.05) except that between low- and intermediate I-risk subcategory (P > 0.05). There were statistical differences for refractory anemia (RA) vs RA with excess blast (RAEB), refractory cytopenias with multilineage dysplasia (RCMD) vs RAEB and RAEB-I vs RAEB-II (P < 0.05).
There were differences in age of disease onset, distribution of WHO, sub-classification and abnormal karyotype in this cohort of MDS patients as compared with those in Europe and Japan. It is helpful in diagnosis, treatment and prognosis to divide RAEB into RAEB-I and RAEB-II. IPSS was well applicable in Chinese MDS patients.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 12/2008; 29(11):723-7.
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ABSTRACT: ObjectiveTo evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients
with non-Hodgkin’s lymphoma.
MethodsThirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell
lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m2 days 1∼3, mitoxantrone 8∼10 mg/m2 day 1, and dexamethasone 20∼30 mg/m2 days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole,
fluconazole, acyclovir and immunoglobulin.
ResultsOf the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR)
rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7%
and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of
partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity
was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4
neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a
median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)%
and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.
ConclusionFMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell
lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.
Chinese Journal of Clinical Oncology 11/2008; 5(6):433-436.
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ABSTRACT: Retroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo.
FIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice.
Muscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24 h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2.
LTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.
Chinese medical journal 07/2004; 117(6):893-8. · 0.86 Impact Factor
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ABSTRACT: To investigate the relationship between interleukin-18 (IL-18) and human acute graft-versus-host disease (aGVHD), 26 patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were included in this study. IL-18 secreted by peripheral blood mononuclear cells (MNCs) was measured by enzyme-linked immunosorbent assay (ELISA) before transplantation and during aGVHD. The results showed that grade I GVHD and grades III-IV GVHD developed in 10 and 5 cases, respectively. The levels in the supernatants of MNCs from patients with aGVHD were significantly higher than those in the cases without aGVHD. The levels of IL-18 were correlated with the severity of aGVHD. It is concluded that IL-18 plays an important role in the development of aGVHD.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 11/2002; 10(5):452-4.
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ABSTRACT: To evaluate the efficacy of combination of mycophenolate mofetil (MMF) with cyclosporine (CsA) and methotrexate (MTX) on prophylaxes of acute graft-versus-host disease (GVHD) in HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT).
Thirty-nine patients with acute leukemia (n = 21) and chronic myeloid leukemia (n = 17) and severe aplastic anemia (n = 1) were treated with allo-PBSCT from HLA matched siblings (n = 36) or unrelated donors (n = 3). Twenty-six patients were in CsA + MTX group. CsA was given at a dosage of 2 mg.kg(-1).d(-1) by continuous intravenous injection for 24 h, since on day(-1) and injection of CsA was changed to oral administration of CsA around day 18. CsA was tapered by 10% per week after day + 90. MTX was given at the dosage of 15 mg at day + 1, and 10 mg at day + 3, + 6 and + 11, respectively. Thirteen patients were included in MMF + CsA + MTX group with the same dosage of CsA and MTX as above but omitted at day + 11. MMF of 2 g/day was added orally from day + 1 to day + 28 post transplantation.
All patients in both groups were successfully engrafted. The days of recovery of neutrophils and platelets were not significantly different between two groups (P > 0.05). The incidence of acute GVHD in MMF + CsA + MTX group (7.6%) was significantly lower than that in CsA/MTX group (46.2%, P < 0.05). Incidence of grade II approximately IV GVHD in MMF group was 0 while that in control group was 23.0%. The incidence of severe mucositis was lower in MMF group (15.4%) than in the control group (30.8%) (P < 0.05).
The regimen of MMF + CsA + MTX for prevention of acute GVHD in allo-PBSCT is more efficient than that of CsA + MTX, without adversely affecting the engraftment and relapse rate.
Zhonghua yi xue za zhi 04/2002; 82(8):507-10.
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ABSTRACT: Embryonic stem cells are continuously growing stem cell lines of embryonic origin. The distinguishing features of ES cells are their capacity to be maintained in an undifferentiated state indefinitely in culture and their potential to develop into various kinds of cells in the body. At molecular level, in vivo and in vitro differentiation of ES cells are similar in many ways. To date, ES cells can differentiate in vitro into myocytes and myocardial cells, neural precursor cells, hematopoietic cells and endothelial cells. Recent evidence suggests that hematopoietic stem cells (HSCs) originate from a region within the embryo proper. It is likely that the genesis of HSCs is regulated by embryonic growth factors, which have not been discovered yet. ES cells have provided a convenient and effective experimental approach to define early hematopoietic process within embryos. Research on ES cells has broad application prospect.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 01/2002; 9(4):372-375.
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ABSTRACT: Human immunodeficiency virus type-I (HIV-I), one kind of lentiviruses, was characterized by a complex genome that encodes two regulatory proteins and four accessory proteins in addition to the common gag, pol and env gene products. So far, a few of different types of replication-defective vectors were constructed, the highest viral titer from one of which was above 10(7) TU/ml. Several studies on packaging cell line found that eliminating the four accessory genes would have few effect on transduction ability of vector and split-genome package system could reduce the possibility of producing replication-competent virus. There are two kinds of characters on HIV-I vectors. Firstly, it was highly efficient in transducing CD34(+) human hematopoietic stem/progenitor cells; secondly, repeated injections of the HIV-I vector into animal did not elicit the rejection response. HIV-I vector had an extensive host range.
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 04/2000; 8(1):75-78.
