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Outcome of acute promyelocytic leukemia with homoharringtonine (HHT) and ATRA.

Ye YUAN ; Wei LI ; Dong LIN ; Ying-chang MI ; Ying WANG ; Hui WEI ; Bing-cheng LIU ; Chun-lin ZHOU ; Kai-qi LIU ; Jin-Yu WANG ; Shu-ning WEI ; Ben-Fa GONG ; Xing-Li ZHAO ; Ming-yuan SUN ; Jian-xiang WAN

Chinese Journal of Hematology.2011;32(11):752-757.

OBJECTIVETo assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen).

METHODS115 APL patients (54 in HHT group, 61 in DNR group) after long-term follow-up were enrolled in the analyses of clinical feature, chromosome karyotype, molecular biology, OS and EFS.

RESULTSThe overall CR of 115 patients was 100%, the median interval to achieve hematological CR was 32 (22 - 43) days, the overall median OS was within 0.23 - 77.34 months, median EFS was within 0.23 - 77.34 months. 3-year OS rate was 93%, 5-year OS rate 93%, 3-year EFS rate 85% and 5-year RFS rate 75% respectively. Converting to PML-RARα PCR-negative after the induction therapy in the HHT and DNR group was 31.3% and 15.5% respectively, at the end of 1 consolidation course was 68.6% and 77.6% respectively, while the remaining 4 patients tested PML-RARα PCR-negative at the end of 2 consolidation courses in the DNR group. While both groups obtained the identical molecular biology relapse rate (9.8% and 8.6%, respectively). Survival analysis indicated that no significant difference was found on OS and EFS between the HHT group and the DNR group (P = 0.206 and 0.506). 5-year OS rate was 87% for the HHT group while 98% for the DNR group, 5-years EFS rate was 80% for the HHT group while 71% for the DNR group. And the risk group was not the factor affecting OS and EFS (P = 0.615 and 0.416). Grade 2 fever in the HHT group was less than in the DNR group during induction therapy. And no difference was found in terms of liver dysfunction, renal dysfunction, cardiac dysfunction, and hematologic toxicity between two groups.

CONCLUSIONOur study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Harringtonines ; administration & dosage ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Tretinoin ; administration & dosage ; Young Adult

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Predictable recurrence by regular monitoring minimal residual disease with flow cytometry in the patients with both AML and ALL: a single-center study of 163 cases.

Chun-rong TONG ; Hui WANG ; Jun-fang YANG ; Yue-hui LIN ; Xian ZHANG ; Jie ZHAO ; Xin-hong FEI ; Jiang-ying GU ; Dao-pei LU

Chinese Journal of Hematology.2011;32(11):748-751.

OBJECTIVETo study the predictable value of monitoring minimal residual disease (MRD) regularly by flow cytometry (FCM) in patients with acute leukemia (AL) in the first complete remission (CR(1)).

METHODSFrom April 2005 to July 2009, AL patients who had got CR(1) after chemotherapy were regularly monitored for MRD in bone marrow by FCM to relapse or to July 2010 in Beijing Daopei Hospital (not including those received stem cell transplantation). The special antibody combinations were employed for each patient according to aberrant expression of leukemia cells. MRD(+) was defined as the aberrant cells more than 0.01%. The probability of continuous CR (CCR) was calculated by Kaplan-Meier formula, and the statistical difference between two CCR probabilities was evaluated by log-rank test.

RESULTSA total of 163 AL patients in CR(1) were monitored to relapse or to July 2010. Among 89 AML patients referred to our hospital within 1 year after diagnosis, 30 cases were in MRD(+) and 59 cases MRD(-) till 12 months following chemotherapy, 3/30 patients in MRD(+) and 47/59 remained in CCR to July 2010. The probability of CCR at 24, 36 months was 13%, 13%in MRD(+) group, 94%, 78% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Among 35 ALL referred to our hospital within 5 months after diagnosis, 13 cases were MRD(+) and 22 cases MRD(-) till 5 months following chemotherapy, 0/13 patients in MRD(+) and 20/22 patients in MRD(-) remained in CCR to July 2010. The probability of CCR at 24, 36 months was 0% in MRD(+) group, 96%, 96% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Over the time point above, all patients with MRD(+) or their MRD from negative to positive relapsed finally, and most patients with MRD(-) remained CCR to July 2010.

CONCLUSIONIt had a clinical prognostic value to monitor MRD regularly by FCM in the patients with AL after CR(1).

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; pathology ; Middle Aged ; Neoplasm, Residual ; diagnosis ; Predictive Value of Tests ; Prognosis ; Recurrence ; Young Adult

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The type I insulin-like growth factor receptor highly expressed in clonal cells of myelodysplastic syndromes.

Qi HE ; Xiao LI ; Zheng ZHANG ; Qing-xia ZHANG ; Lian-ping YANG

Chinese Journal of Hematology.2011;32(11):744-747.

OBJECTIVETo probe the expression level of insulin-like growth factor-I receptor (IGF-IR) in malignant clone cells of myelodysplastic syndromes (MDS).

METHODThe combination of fluorescence in situ hybridization (FISH) and immunochemistry (alkaline phosphatase anti-alkaline phosphatase, APAAP) was used to detect the expression of IGF-IR in the bone marrow cells of 40 MDS patients with abnormal karyotypes.

RESULTSThe average IGF-IR expression level on the clone cells \[(84.5 ± 14.2)%\] from the MDS cases was markedly elevated compared to the corresponding level on normal cells \[(11.4 ± 12.1)%\]. And the percentages of malignant clone cells in all 40 MDS cases were significantly correlated with the relevant percentages of IGF-IR positive nucleated cells (r = 0.929, P < 0.01).

CONCLUSIONSIGF-IR might be taken as a marker of clone cells in MDS for its trait to malignant proliferation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Clone Cells ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; pathology ; Receptor, IGF Type 1 ; metabolism ; Young Adult

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Differential proteomic analysis in human umbilical cord mesenchymal stem cells induced by cobalt chloride.

Hui-lan ZENG ; Qi ZHONG ; Hai-tao JIA ; Yong-liang QING ; Qian-qian BU ; Xin-ai HAN ; Hong-wei LIU

Chinese Journal of Hematology.2011;32(11):739-743.

OBJECTIVETo analyze the differential proteomics in human umbilical cord mesenchymal stem cells (MSC) induced by chemical hypoxia-mimetic agent cobalt chloride (CoCl(2)) by two-dimensional gel electrophoresis (2-DE) and mass-spectrometry.

METHODS2-DE was performed to separate proteins from treated and untreated human umbilical cord MSC with CoCl(2). 2-DE images were analyzed by ImageMaster 2D Platinum software 6.0. The differential expressed proteins was identified by MALDI-TOF-MS. The differential proteins were classified based on their functions.

RESULTS2-DE reference patterns of CoCl(2) treated human umbilical cord MSC were established. A total of twenty-six differential proteins were identified, of them eleven proteins were up-regulated and fifteen down-regulated. Their biological functions involved in carbohydrate metabolism, protein metabolism and modification, lipid metabolism, coenzyme and prosthetic group metabolism, cell cycle, immunity and defense, cell structure and motility, signal transduction, protein targeting and localization, neuronal activities, muscle contraction, etc. Peroxiredoxin1 (Prdx) was down-regulated, whereas alpha-enolase (ENO1) and vesicle amine transport protein 1 homolog (VAT1) up-regulated.

CONCLUSIONThe effects of hypoxia on human umbilical cord MSC were participated by multiple proteins and involved in multiple functional pathways.

Cobalt ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; Proteome ; analysis ; Proteomics ; Umbilical Cord ; cytology ; drug effects

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Experimental study on rejection of allogeneic donor bone marrow cells in sensitized recipients.

Lü-hong XU ; Jian-pei FANG ; Wen-jun WENG ; Hong-gui XU ; Qi-xiang YE

Chinese Journal of Hematology.2011;32(11):734-738.

OBJECTIVETo establish a murine model of sensitization, and investigate the effect and mechanism of sensitization on allogeneic donor bone marrow cells (BMCs).

METHODSSensitized BALB/c mice were established by transfusions of allogeneic splenocytes. The donor reactive antibodies were detected by binding and complement-dependent cytotoxicity assays. After irradiation, 1 × 10(7) BMCs of C57BL/6 donor mice were injected into non-sensitized or sensitized BALB/c recipient mice. The distribution pattern of donor BMCs in peripheral blood, spleen and bone marrow of recipient mice were analyzed at different time points (2 h, 12 h and 48 h) post transplantation. Hematopoietic recovery post transplantation was assessed, and survival was monitored. Moreover, sera and splenocytes derived from non-sensitized or sensitized recipients were incubated with allogeneic BMCs in vitro, and the cytotoxic indexes were calculated in the immune experiments.

RESULTSThe binding and complement-dependent cytotoxicity assays showed that a high level of donor reactive antibodies was presented in sensitized sera. Compared with the non-sensitized recipients, the homing assay showed significantly decreased distributions of allogeneic donor BMCs in peripheral blood, spleen and femur of sensitized recipients. Non-sensitized recipients survived long term after irradiation, while all the sensitized recipients died within 12-15 days. Fourteen days post transplantation, the white blood cells and BMCs of non-sensitized recipients were (3240 ± 300) × 10(6)/L and (396 ± 27) × 10(6)/femur, respectively; while the white blood cells and BMCs of sensitized recipients were (320 ± 80) × 10(6)/L and (6 ± 2) × 10(6)/femur, respectively; the differences were statistically significant between this two groups (P < 0.05). Seven days post transplantation, the percentage of donor cells in bone marrow of non-sensitized and sensitized recipients was (48.07 ± 4.70)% and (0.77 ± 0.11)%, respectively, and the differences were statistically significant (P < 0.05). Furthermore, the white blood cells and BMCs following transplantation decreased along with time in sensitized recipients. The immune experiments of complement-dependent cytotoxicity reaction, cytotoxic T lymphocytes reaction and antibody-dependent cellular cytotoxicity showed the cytotoxic indexes were higher in sensitized group than the non-sensitized group.

CONCLUSIONA sensitized model was established by transfusions of allogeneic spleen cells. Allogeneic donor BMCs were rejected in sensitized recipients, and its mechanism might be through immune impairment pathways.

Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Disease Models, Animal ; Graft Rejection ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Tissue Donors ; Transplantation, Homologous

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Autologous hematopoietic stem cell transplantation following bortezomib-based chemotherapy for one case with POEMS syndrome.

Ling-hao LI ; Ri ZHANG ; Xiao-wen TANG

Chinese Journal of Hematology.2011;32(11):733-733.

Adult ; Boronic Acids ; therapeutic use ; Bortezomib ; Combined Modality Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; POEMS Syndrome ; therapy ; Pyrazines ; therapeutic use

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Analysis of high risk factors for relapse of leukemia after allogeneic hematopoietic stem cell transplantation.

Jia CHEN ; Feng CHEN ; Aining SUN ; Hui-ying QIU ; Yue HAN ; Xiao-wen TANG ; Zheng-zheng FU ; Miao MIAO ; Guang-sheng HE ; Zheng-ming JIN ; De-pei WU

Chinese Journal of Hematology.2011;32(11):729-733.

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

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Secondary polycythemia due to obstructive sleep apnea hypopnea syndrome: a case report.

Li-yan LIANG ; Feng-kui ZHANG

Chinese Journal of Hematology.2011;32(10):728-728.

Humans ; Male ; Middle Aged ; Polycythemia ; etiology ; Sleep Apnea, Obstructive ; complications

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Research advances of downstream signal pathways of membrane factor receptors on hematopoietic cells of the patients with myelodysplastic syndrome.

Bing-nan LIU ; Zong-hong SHAO

Chinese Journal of Hematology.2011;32(10):713-716.

Humans ; Membrane Proteins ; metabolism ; Myelodysplastic Syndromes ; metabolism ; Receptors, Colony-Stimulating Factor ; metabolism ; Signal Transduction

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Microcytic hypochromic anaemia caused by inborn errors of iron metabolism.

Yuan-yuan XIONG ; Feng-kui ZHANG

Chinese Journal of Hematology.2011;32(10):710-712.

Anemia, Hypochromic ; etiology ; Humans ; Iron ; metabolism ; Protein Deficiency ; complications ; congenital ; Transferrin ; deficiency

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