Clinical resarch of decitabine combined with modified CAG regimen for treatment of relapsed or refractory acute myeloid leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was to investigate the therapeutic effectiveness and side effect of decitabine combined with modified CAG regimen for relapse or refractory patients with acute myeloid leukemia.</p><p><b>METHODS</b>Ten patients suffered from relapsed or refractory acute myeloid leukemia from January 2013 to July 2013 were analyzed retrospectively, and the clinical characteristics, therapeutic effectiveness, side effect were observed. Among 10 patients 7 patients were males and 3 patients were females, the ratio of male to female was 7:3, median age was 45 (17-61) years.</p><p><b>RESULTS</b>After treatment by using decitabine combined with modified CAG regimen, 7 patients achived complete remission, 1 patient achived partial remission, 2 patient did not achieve remission, the overall remission rate was 80% (8/10), the median time of white blood cell count recovery was 18.5 (5-28) days, median time of platelet level recovery was 19 (12-29) days. The main side effects of treatment were myelosuppression. There was no new lung infection in all cases, one case died of exacerbation of primary lung infection after therapy.</p><p><b>CONCLUTION</b>The treatment of decitabine combined with modified CAG regimen for relapsed and refractory AML shows high response rate, low side effects, so it worthy to further clinical study.</p>

A rare case of acute promyelocytic leukemia accompanied by benign craniopharyngioma / 中国实验血液学杂志

The purpose of study was to analysis the clinical manifestation and treatment protocol of acute promyelocytic leukemia (APL) accompanied by craniopharyngioma so as to promote the understanding of this disease. The APL was diagnosed by morphologic examination of bone marrow cells, the leukemia bone marrow cells were analyzed by immunophenotyping technique, the qualitative and quantitative changes of PML-PARα fusion gene before and after treatment were monitored by using molecular biological test; the cytogenetic features were analyzed by using conventional karyotype and FISH analysis. The results indicated that the clinical manifestation of this disease was diverse and disease status was complex. The good therapeutic efficacy could be achieved, the misdiagnosis and delayed treatment could be avoided through early detection, timely treatment and multidisciplinary cooperation. It is concluded that when other clinical symptoms reappear after APL achieves remission, the possibility of second tumor must be considered, the clinical presentation should be carefully monitored, the early detection and timely treatment should be performed to improve the survival of patients.

Analysis of empirical treatment for newly diagnosed acute promyelocytic leukemia combined with disseminated intravascular coagulation / 中国实验血液学杂志

This study was aimed to explore the clinical characteristics and optimal therapeutic methods for newly diagnosed acute promyelocytic leukemia (APL) combined with disseminated intravascular coagulation (DIC) so as to guide the clinical therapy. The clinical date and therapeutic outcome of 25 cases of APL combined with DIC treated from January 2008 to March 2013 in our department were analysed retrospectively. The 25 patients were given ATRA 20 mg orally twice a day and arsenic trioxide (ATO) 10 mg intravenously once a day to induce differentiation therapy, the chemotherapy was added after degranulation of promyelocytes. At the same time the platelets, fresh frozen plasma, fibrinogen, cryoprecipitate,prothrombin complex and amino methylbenzoic acid, low molecular weight heparin were given to treat DIC. According to the laboratorial examination of coagulation and fibrinolysis, the medication was adjusted.The white blood cell count, platelet level, prothrombin time (PT), partial thromboplastin time of plasma (APTT), fibrinogen level were detected, and the relation of those factors and age with bleeding severity was analyzed by multivariate manner. The results showed that among 25 patients with APL (low-risk 5 cases, intermediate risk 13 cases and high risk 7 cases), 22 cases combined with DIC, incidence of DIC was 88%. Out of 22 patients with DIC 21 patients (95.5%) were corrected, except 1 case death. After the first course of treatment, 23 cases (92%) gained complete remission (CR) with average CR time 31.8 ± 7.2 days. During the induction of CR, the average platelet transfusion level was 75.68 ± 55.88 U, the RBC level was 8.90 ± 5.69 U, the average level of fresh frozen plasma transfusion of APL patients with DIC was 21.92 ± 19.32 U. The recovery time of platelet level to normal was 29.3 ± 9.3 days, the recovery time of PT, APTT, FDP and fibrinogen to normal were 12.7 ± 9.5 days, 11.6 ± 8.6 days, 16.0 ± 9.3 days and 125.3 ± 85.3 days respectively. The multivariate analysis showed that WBC count at onset was >10 × 10(9)/L and APTT was prolonged. These two factors were main reasons resulting in severe bleeding. It is concluded that the newly diagnosed APL always combined with DIC, therefore in the early phase of disease active transfusion of blood products, application of anti-coagulation and anti-fibrinolytic drugs as well as heparin should be performed; the coagulation function should be as soon as recovered to normal so as to early correct DIC. These measures can significantly decrease the mortality of APL patients resulting from DIC. The hyperleukocytosis and prolonged APTT are the main factors for severe bleeding.

Clinical analysis of 15 patients with primary granulocytic sarcoma / 中国实验血液学杂志

This study was purposed to analyze the clinical feature,diagnosis and treatment efficacy of primary granulocytic sarcoma (PGS). A total of 15 patients with PGS from January 2008 to March 2013 was evaluated retrospectively, among 15 patients 8 patients were treated with chemotherapy (chemotherapy alone,chemotherapy combined with local irradiation,chemotherapy combined with surgical resection or bone marrow transplantation), 7 patients were treated without chemotherapy, but were treated with surgical resection or surgical resection plus local irradiation.The chemotherapy method for PGS patients was similar as treatment of acute myeloid leukemia. The results indicated that the proportion of disease progression into bone marrow abnormality in patients treated with chemotherapy and in patients treated without chemotherapy was 25% and 85.7% respectively, suggesting that the chemotherapy can reduce the incidence of progression into bone marrow abnormality (P < 0.05). The average survival time of PGS patients treated with chemotherapy or without chemotherapy was 26.063 ± 14.97 and 12.214 ± 6.83 months (P < 0.05),suggesting prolonging of survival time of patients treated with chemotherapy, moreover 2 patients who were treated using chemotherapy combined with bone marrow transplantation still alive now,and their living times were 39 months and 45 months respectively. It is concluded that intensive chemotherapy similar as treatment of AML can decrease the probability of disease progressing into bone marrow abnormality, and if chemotherapy combines with bone marrow transplantation, the survival time of PGS patients can be longer. In this aspect, the efficacy of treatment and survival time at home and abroad are similar.

Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺ / 中国实验血液学杂志

This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

Analysis of (18)F-FDG PET/CT features and clinical manifestations in one case of subcutaneous lymphomatoid granulomatosis / 中国实验血液学杂志

This study was aimed to investigate the pathology, MICM classification, PET/CT characteristics and therapeutical experience of subcutaneous soft tissue muscle gap lymphomatoid granulomatosis (LYG) through analysis of a cases of LYG. The pathologic changes of LYG were assayed by using immunohistochemistry method;the immuno-phenotypes were detected by flow cytometry. The nested multiplex PCR was used to detect the expression and mutation of abnormal genes; the real-time fluorescence quantitative PCR was used to detect the EBV-DNA copies. The clinical staging was performed by means of fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). The results showed that at onset of disease the clinical manifestations of patient presented only a mass in right thigh and swelling of right submandibular lymph nodes. However, PET/CT revealed that the abnormal image in multiple soft tissue accompanied by increasing metabolic activity (SUVmax = 12.8), these pathologic changes were involved in lung, thyroid, lymphonodes and stomach. The right thigh mass biopsy confirmed the histological diagnosis of grade II LYG. The bone marrow smear showed no abnormal tumor cell infiltration, the immunophenotyping detection revealed that the proportion of NK cells increased with phenotypic abnormality, the karyotype was 46, XY[24], the expression and mutation of abnormal gene not could be detected, and the EBV-DNA level was <10(2) copies/ml. After 2 cycles of treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone(R-CHOP), the images of increasing metabolic activity in subcutaneous soft tissue gap disappeared, but the partial increasing metabolism focus could be observed in soft tissue of left knee hollow. The patient achieved partial remission. It is concluded that LYG is an extremely rare hematopoietic malignancy, the incidence rate is very low. Subcutaneous soft tissue muscle gap LYG literature was not reported in domestic and foreign literatures.Its pathogenetic remains unclear. A standard treatment protocol for LYG has not yet been established. PET/CT can find more lesions that not could be found in the clinical examination. The (18)F-FDG PET/CT is an efficient tool for the LYG in diagnosis, staging and treatment. Therefore, increased SUV(max) in FDG-PET may be useful for diagnosis of LYG.

Clinical analysis of acute myeloid leukemia with t(8;21) (q22;q22) and loss of Y chromosome / 中国实验血液学杂志

This study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with t (8;21) (q22;q22) and loss of Y chromosomes. Clinical data of 267 cases of AML were collected from January 2010 to June 2013. Among 267 AML, there were 13 cases with t (8;21) (q22;q22) and loss of Y chromosomes. The clinical data including clinical indicators, treatment protocols, curative effect and prognosis were analyzed retrospectively. The results showed that after normalized chemotherapy, there were 4 patients with complete remission at the first cycle of treatment, 4 patients with complete remission at the second cycle, 4 patients with complete remission at the third cycle, but one patient without complete remission after 4 cycles. There were 6 patients who did not relapse during consolidation and intensive therapy. Among these 6 patients, 4 cases accepted chemotherapy combined with transplantation, other 2 cases accepted chemotherapy. In the remainder 6 patients, 4 cases relapsed once, one cases relapsed twice, 1 cases relapsed for three times. Moreover, 2 cases who accepted the chemotherapy and auto-hematopoietic stem cell trans-plantation, were diagnosed as relapse, after accepted allo-hematopoietic stem cell transplantation, currently are in disease-free status. In follow-up period, the relapse-free survival (RFS) time was 4.67 ± 3.45 months in chemotherapy group, the RFS time is 34.17 ± 21.37 months in chemotherapy and transplantation group. The chemotherapy combined with transplantation extended the RFS time (P < 0.05). It is concluded that the NCCN guide indicates that AML with t (8;21) ( q22;q22) showed a good prognosis. but the clinical course of treatment confirmed that the prognosis of AML patients with t (8;21) (q22;q22) and loss Y chromosomes is poor, including uneasy remission and easy relapse, for improving the prognosis of these patients, the hematopoietic stem cell transplantation should be recommended.

Analysis of efficacy and prognosis of induction chemotherapy in 76 elderly patients with acute myeloid leukemia (non-APL) / 中国实验血液学杂志

This study was purposed to investigate the clinical features, diagnosis, treatment and prognosis of elderly patients with acute myeloid leukemia (AML) (non-APL). The clinical data of 76 elderly ( ≥ 60 old years) AML (non-APL) patients from January 2000 to January 2010 were analyzed retrospectively. According to treatment methods,the 76 patients were divided into 2 groups: induction chemotherapy group (51 cases) and best supportive treatment group (25 cases). The patients in induction chemotherapy group received the cytarabine-based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the patients in best supportive treatment group received supportive treatment including hydroxyurea, blood transfusion and so on. The clinical features, diagnosis, treatment and prognosis between 2 groups were compared. The results showed that the median survival times of patients in induction chemotherapy and best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months respectively, there was significantly statistical difference in median survival time between 2 groups(P < 0.01) suggesting that the induction chemotherapy obviously prolonged the survival time of elderly CML patients. The 5 patients in induction chemotherapy group survived more than 60 months, one of them survived more than nine years. After the first cycle of chemotherapy, the complete remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of patients in induction remission stage was 13.7% (7/51) in induction chemotherapy group; no 1 case in best supportive treatment group reached to CR. The CR rate of patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles were 3 (1-14). The follow-up found that the 3 months-survival rate of patients was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1 year-survival rate of patients was 29% and 13%, the 5 year-survival rate of patients was 13% and 0% in induction chemotherapy and best supportive treatment groups respectively, showing that the survival of patients in induction chemotherapy group was better than those in best supportive treatment group. A total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response to the first cycle of chemotherapy, the survival time of these patients was not statistically significantly different from that of patients in best supportive treatment group. It is concluded that the induction chemotherapy can significantly improve the prognosis of elderly patients with AML, and prolong their median survival time. The induction remission rate in elderly patients with AML is lower than that of younger patients. The MA regimen is better than DA, HA, IA and CAG, there is individual difference in the elderly patients with AML, If the first cycle of chemotherapy has not reached to CR or PR, the best supportive treatment may be considered. The low toxicity, efficient and well-tolerated chemotherapy regimens may be chosen to prolong the survival time of the elderly patients with AML (non-APL).

Efficacy of liver transplantation for acute hepatic failure caused by reactivation of hepatitis B virus infection after chemotherapy and radiotherapy for diffuse large B-cell lymphoma / 中国实验血液学杂志

This study was aimed to investigate the morphological, biological ,clinical and therapy features in a special case of primary gastric non-Hodgkin's lymphoma (PG-NHL) through analysis of PG-NHL patient who developed fulminating hepatitis following chemotherapy and radiotherapy and thus received liver transplantation (LT). The morphological changes of cells were analyzed by bone marrow smear, the expression and mutation of abnormal genes were detected by nested multiplex PCR, and HBV-DNA copies were detected by real-time fluorescence quantitative PCR (FQ-PCR). The results showed that at onset of disease, patient was diagnosed as primary gastric non-Hodgkin's lymphoma (PG-NHL) with HBsAg(+) and HBVDNA(-). LUGANO stage was Ia. aaIPI score was 0.The patient was treated with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), rituximab maintenance treatment and radiotherapy. During the treatment, the patient has taken entecavir, 1 week later after the radiotherapy (2 months later after the chemotherapy), then the entecavir was discontinued. Six months later HBV DNA(+), the progressive acute hepatic failure (AHF) happened to the patient, who thus received phylogenetic right liver transplantation (LT). He has survived for 3 years after LT so far. The liver function of patient was normal more than 3 years after LT. The patient was checked regularly by PET-CT, and his PG-NHL continue complete remission(CR). It is concluded that the patients receiving chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver function and HBV reactivation signs. HbsAg positive patients should receive preventive antiviral therapy. After chemotherapy or immunosuppressive therapy, the patients should be given antiviral maintenance therapy, and the liver damage should receive the hepatoprotective and effective support treatment, LT is necessary and feasible to obtain long-term survival.

Improvement effect of bacterium derived oligonucleotides on maturation of K562/A02 cells derived dendritic cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the maturation effect of CpG2006 and phosphodiester oligonucleotides on leukemia-derived dendritic cells.</p><p><b>METHODS</b>Leukemia cells K562/A02 were induced into dendritic cells by rhGM-CSF and rhIL-4. After 7 days induction, the cell-morphology was observed, the immunophenotype of cells was detected by flow cytometry and the cell function was evaluated by allogeneic mixed lymphocyte reactions, CTL responses and secretion of IL-12 and IL-6. Then a CpG oligonucleotide CpG2006, two synthetic bacterial phosphodiester oligonucleotides A-ODN and T-ODN were added to these leukemia-derived DCs. Three days later, the DCs were re-detected by the above-mentioned methods.</p><p><b>RESULTS</b>After induced by CpG2006, A-ODN or T-ODN, the leukemia-derived DCs with typical dendritic morphology were increased. The expressions of CD83, HLA-DR and CD86 were (65.5 +/- 8.4)%, (32.0 +/- 4.3)% and (18.6 +/- 3.2)% respectively in day 7 leukemia-derived DCs, raised to (88.9 +/- 3.6)%, (53.9 +/- 3.2)% and (39.9 +/- 7.3)% respectively after exposing CpG2006 for 3 days; increased to (97.0 +/- 5.3)%, (63.9 +/- 7.3)% and (40.2 +/- 7.4)% respectively after treated by A-ODN; and further increased to (93.26 +/- 4.65)%, (58.3 +/- 5.6)% and (36.2 +/- 6.8)% respectively after treated by T-ODN. These results was markedly different than unaffected cells did. These DCs induced by the above-mentioned three oligonucleotides could upregulate significantly the capacity for stimulating allogeneic T cells. They could also induce CTL to generate specific cytotoxic activity against K562/A02 cells. The secretion of IL-6 and IL-12 was increased remarkably.</p><p><b>CONCLUSION</b>CpG2006, as well as two phosphodiester oligonucleotides can induce leukemia-derived DCs maturation.</p>