An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial).

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has been demonstrated to have comparable effectiveness or better to ATRA and chemotherapy (CHT) in non-high-risk acute promyelocytic leukemia (APL). However, the efficacy of ATRA-ATO compared to ATRA-ATO plus CHT in high-risk APL remains unknown. Here we performed a randomized multi-center non-inferiority phase III study to compare the efficacy of ATRA-ATO and ATRA-ATO plus CHT in newly diagnosed all-risk APL to address this question. Patients were assigned to receive ATRA-ATO for induction, consolidation, and maintenance or ATRA-ATO plus CHT for induction followed by three cycles of consolidation therapy, and maintenance therapy with ATRA-ATO. In the non-CHT group, hydroxyurea was used to control leukocytosis. A total of 128 patients were treated. The complete remission rate was 97% in both groups. The 2-year disease-free, event-free survival rates in the non-CHT group and CHT group in all-risk patients were 98% vs 97%, and 95% vs 92%, respectively (P = 0.62 and P = 0.39, respectively). And they were 94% vs 87%, and 85% vs 78% in the high-risk patients (P = 0.52 and P = 0.44, respectively). This study demonstrated that ATRA-ATO had the same efficacy as the ATRA-ATO plus CHT in the treatment of patients with all-risk APL.

[Relationship between the Therapeutic Dose of Arsenic Trioxide and Relapse in Acute Promyelocytic Leukemia].

OBJECTIVE: To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO. METHODS: The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve. RESULTS: Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg. CONCLUSION: The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.

[Relationship between Peripheral Blood White Blood Cell Count and Early Death Rate in Patients with Acute Promyelocytic Leukemia].

OBJECTIVE: To investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL). METHODS: Through retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years. RESULTS: There was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×109/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×109/L(P<0.05) and 91.5×109/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05). CONCLUSION: The highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.

[Risk Factors and Therapeutic Outcome of Intestinal Acute Graft Versus Host Disease in Acute Leukemia Patients after Haploidentical Peripheral Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the risk factors and therapeutic outcome of acute graft versus host disease (aGVHD) in patients with acute leukemia after haploidentical peripheral hematopoietic stem cell transplantation. METHODS: The clinical data of 19 cases of acute leukemia underwent haploidentical hematopoietic stem cell transplanttion during January 2010 and December 2010 were retrospectively analyzed. The effects of patients sex, donor-recipient sex difference, donor age, conditioning regimen, dosage of anti-thymocyte globulin(ATG), mononuclear cell and CD34+ cell counts on the intestinal aGVHD were analyzed by Logistic regression. RESULTS: Intestinal aGVHD occurred in 5 cases with 1 case at stage II 3 cases at stage III and 1 case at stage IV on the 7th, 22th, 27th, 70th and 154th day after transplantation, respectively. Single factor analysis showed that the patient's sex, donor-recipient sex difference, donor age, dosage of ATG, mononuclear cell and CD34+ cell counts were not related with the occurrence of the intestinal aGVHD, and the conditoning regimen was the risk factor for the intestinal aGVHD. 2 cases among 5 cases with intestinal aGVHD were treated with methylprednisolone at dosage of 1 mg/kg per day, 1 case was treated with methylprednisolone therapy combined with tacrolimus. 2 cases of methylprednisolone-resistance were treated with CD25 monoclonal antibody. Intestinal aGVHD of all patients was improved after the above-mentioned treatment. CONCLUSION: Conditioning regimen of haploidentical peipheral hematopoieitc stem cell transplantaion has effects on the intestinal aGVHD, which needs to be confirmed by further research.

[WT1 gene expression difference in leukemia and non-leukemia and its clinical significance].

This study was aimed to investigate the expression level of Wilms' tumor 1( WT1) gene in hematologic neoplasm (leukemia, multiple myeloma and lymphoma) patients and its clinical significance. Real-time quantitative polymerase chain reaction (RQ-PCR) was used to detect the copy number of WT1 gene and reference gene (ALB) in bone marrow cells of 228 patients with hematologic neoplasm in our hospital. The gene expression level was determined by using the ratio of the copy number of WT1 gene and reference gene. The results showed that the WT1 expression level between male and female patients was not statistically significantly different (P > 0.05). All the patients were divided into 3 groups: the group aged under 19, the group aged between 19-50, and the group aged over 50; the WT1 expression level among the three groups were not statistically significantly different (P > 0.05) . The above-mentioned patients were redivided into the groups aged under 45 and over 45, the difference between them was not statistically significant (P > 0.05). The difference of WT1 expression level between newly diagnosed patients and treated patients with hematologic neoplasm was statistically significant (P < 0.01), but no statistically significant difference of WT1 expression was found (P > 0.05) at each stage within 3 years after treatment, however, among them the difference between newly diagnosed leukemia patients and treated leukemia patients was very statistically significant (P < 0.01), while the difference between newly diagnosed and treated non-leukemia patients was not statistically significant (P > 0.05). The expression difference of WT1 between leukemia and non-leukemia patients was very statistically significant (P < 0.01), the difference between the newly diagnosed leukemia and non-leukemia patients also was very statistically significant (P < 0.01). The difference of WT1 expression between treated leukemia and non-leukemia patients was not statistically significant (P > 0.05). It is concluded that the WT1 expression level in leukemia patients can be a reliable marker to evaluate the prognosis of newly diagnosed leukemia and the curative effect for minimal residual disease. No WT1 expression difference has been found before and after treatment among the patients with non-leukemia, such as multiple myeloma and lymphoma, therefore, which should be furtherly explored.

[Relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allo-hematopoietic stem cell transplantation].

This study was aimed to investigate the relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allo-hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 37 patients received allo-HSCT in our hospital were analyzed retrospectively. The 37 patients were divided into agranulocytosis and non-agranulocytosis groups according to the recipient's leukocyte count at reinfusion, and were divided into the high dose and low dose groups according to the median number of reinfused mononuclear cells (MNC) and CD34(+) cells. Then, hematopoietic reconstructions,GVHD, relapse and death rates of patients were compared. The results showed that the hematopoietic reconstruction of patients in non-agranulocytosis group and high dose MNC group were earlier than that in agranulocytosis group and low dose MNC group. There was no significant difference of hematopoietic reconstruction between the groups of high dose CD34(+) cells and low dose CD34(+) cells. The GVHD incidence was higher in high dose MNC group and non-agranulocytosis group than that in low dose MNC group and agranulocytosis group (P < 0.05). There were no statistical differences of relapsed and death rates between different reinfused number of HSC and recipient's leukocyte count at reinfusion.It is concluded that the infused MNC number and the recipient's leukocyte count at reinfusion in allo-HSCT correlated with hematopoietic reconstruction, the GVHD incidence is high in high dose MNC and non-agranulocytosis groups, the reinfused HSC volume and the recipient's leukocyte count at reinfusion not significantly relate with relapse and death rates.

[Effect of dexamethasone on G-CSF mobilization of peripheral blood stem cells in healthy donors and hematopoietic reconstruction in the recipients].

This study was aimed to investigate the effects of different mobilization methods on mobilization and collection of peripheral blood stem cells in healthy donors and the adverse effect of collection, as well as hematopoietic construction in recipients. A total of 43 donors between January 2008 and May 2013 were divided into the simple mobilization group and the combined mobilization group. The simple group was subcutaneously injected with 5.0-10.0 µg/(kg·d) recombinant human granulocyte colony-stimulating factor (rhG-CSF), and the combined mobilization group was treated with rhG-CSF and intravenously dripped with 10 mg dexamethasone for 2-4 hours before collection. The acquisition and count of MNC and CD34(+) cells in different groups, the relationship between the stem cells and MNC count in blood before collection, and the adverse reactions were analyzed; the hematopoietic reconstruction of recipients was investigated. The results showed that the hematopoietic stem cell number of the two groups meet the demands. The count of MNC and CD34(+) cells in the simple mobilization group was more than that in the combined mobilization group. The MNC count in two groups positively correlated with peripheral blood MNC count before collection. The decline of hemoglobin and platelet levels was more obvious in the simple mobilization group than that in combined mobilization group. The adverse reactions of collection in the simple mobilization group could be well tolerated and reversed. There was no adverse reaction in the combined mobilization group. The differences of conditioning regimens between two groups were not statistically significant and the hematopoietic reconstruction time of combined group was shorter than that in the simple mobilization group.It is concluded that the adverse reactions in process of collection can be reduced, and enough hematopoietic stem cells can be collected by G-CSF plus dexamethasone in mobilization of peripheral blood stem cells. The count of MNC in peripheral blood before collection can be still used as a reference index to evaluate the acquisition of MNC. Especially the combination with dexamethasone for stem cell mobilization can promote the hematopoietic reconstruction of the recipients.