Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease.@*METHODS@#The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed.@*RESULTS@#The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy.@*CONCLUSION@#The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.

Clinical Retrospective Analysis of Chronic Myeloid Leukemia in Myeloid Blast Crisis / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze the clinical manifestation, laboratorial test features and prognosis of patients with CML in myeloid blast crisis.@*METHODS@#The clinical data of 10 patients with CML in myeloid blast crisis admitted in Chinese PLA General Hospital from June 2011 to May 2018 were collected, and their clinical features, laboratorial data and long-term survival were analyzed.@*RESULTS@#The median age of these 10 cases was 32.5 (23-73) years old. Nine cases had chronic phase history. The median chronic phase was 17(4-84) months. All the 10 cases had splenomegaly; B-ultrasonography showed that the median spleen size was 5.2 (4-7.8) cm in thickness, and 14.6 (11.4-19.8) in length. When chronic myeloid leukemia was in blast crisis, the median WBC count was 41.705（11.9-344.41）×10 /L and the median platelet count was 159 (13-2326) ×10 /L. The Ph+ chromosome and BCR-ABL1 fusion gene coulld be detected in all the cases. The chromosome karyotyping showed that additional chromosome abnormalities were found in 5 cases. One case was of low diploid, and two cases were with complex karyotype. ABL1 mutation was detected in 6 out of these 10 cases. ABL1 T315I mutation was detected in 2 of them and one was with deletion of combined P53 in genetic tests. The median follow-up time was 10.5(0.2-78) months. There were 5 cases treated sequentially by chemotheraphy with or without TKI and allo-HSCT. Three cases reached CP2 before transplantation. Among them, two cases still survived without progression for 67 months and 69 months after the transplantation respectively. One case died of transplantation-related mortality (suffered from cerebral hemorrhage 7 months after the transplantation). Two cases were NR before the transplantation, and both died of disease relapse or progression at the time points of one or three months after the transplantation. Five cases treated by TKI ± chemotheraphy and without HSCT succumbed to disease progression. The median time was 6(0.2-22) months.@*CONCLUSION@#CML patients in myeloid blast crisis treated by chemotheraphy combined with TKI gain CP2, the survival time of patients treated by sequential allo-HSCT is prolonged.

Safety and Effectiveness of High Dose Tigecycline for Treating Patients with Acute Leukemia after Ineffctiveness of Carbapenems Chemotherapy Combinating with Febrile Neutropenia: Retrospective study / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia.</p><p><b>METHODS</b>The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared.</p><p><b>RESULTS</b>Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05).</p><p><b>CONCLUSION</b>The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.</p>

Retrospective Study of Ph/BCR-ABLAcute Myelogenous Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical manifestation, features of laboratorial examination results and prognosis of patients with Ph/BCR-ABLacute myelogenous leukemia(AML).</p><p><b>METHODS</b>The clinical data of 5 AML patients with Ph/BCR-ABLadmitted in Department of Hematology of Chinese PLA general hospital from July 2007 to May 2015 were collected and their clinical characteristics, laboatorial examination results and long-term survival were analyzed.</p><p><b>RESULTS</b>The median age of 5 cases was 39 years old, and 2 cases with splenomegaly. All the cases were assayed for BCR-ABL fusion gene, and 2 of them were accompanied with other molecular abnormalities. In 4 cases, Ph chromosome was not found in one case, and one was with complex karyotype. 3 cases still are live till now and are treated by traditional chemotherapy combined with TKI, and consolidated by allo-HSCT. One case treated by traditional chemotherapy survived for 6 months. And one case treated by traditional chemotherapy combined with TKI survives till to now.</p><p><b>CONCLUSION</b>The survival time of Ph/BCR-ABLacute myelogenous leukemia is improved by the traditional chemotherapy combined with TKI and the consolidation with allo-HSCT.</p>

Imatinib Combined with VP Low Dose Regiment for Treating Newly Diagnosed Adult Patients with Ph-positive ALL / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the inductive therapeutic effects of imatinib combined with VP low dose regiment on adult patients with Ph-positive acute lymphoblastic leukemia (Ph(+) ALL).</p><p><b>METHODS</b>Fourteen newly diagnosed adult patients with Ph(+) ALL were treated with VP regimen, and imatinib (400 mg/d) was added at the 8(th) day. VP regimen would be stopped when neutropenia lasted for 1 week or complicated with infection, fever, etc. Therapeutic effects were assessed by bone marrow morphology and quantitative analysis of BCR/ABL:ABL at the 28(th) - 33(rd) day. Patients could be treated with imatinib combined with chemotherapy for consolidation and maintenance therapy or were treated with allogeneic hematopoietic stem cell transplantation after complete remission.</p><p><b>RESULTS</b>Fourteen cases obtained CR1 after first course of treatment, the median decline of BCR/ABA:ABL was 55.89 (10.25 -180.97) %; during the induction chemotherapy, pulmonary infection occurred in 3 patients, diarrhea in 1 patients, facial edema in 3 patients, however, all these patients were cured after symptomatic treatment, only 1 patient died of relapse after transplantation.</p><p><b>CONCLUSION</b>In the period of tyrosine kinase inhibitor (TKI), inductive chemotherapy combined with imatinib and low dose VP can obtaine satisfactory CR rate and decrease the toxicity of the traditional drugs. It is suggested that TKI combined with VP regimen chemotherapy can achieve CR1 and make possible for allo-HSCT, from which patients can achieve the long-term survival.</p>

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.

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.

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.

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.

Protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapeutic agents / 中国实验血液学杂志

The aim of this study was to observe the protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapy in patients with leukemia. The clinical data of protective effect were analyzed retrospectively from January 2010 to April 2012. A total of 62 acute leukemia patients were divided into A group (27 cases) and B group (35 cases), the polyene phosphatidyl choline combined with ademetionine or combined with compound glycyrrhizin were given in A and B group, respectively. The changes of liver function were observed after 2 weeks, 5 patients in B group suffered from acute liver injury were treated by ademetionine as rescue therapy. Liver function was compared before and after treatment. The results showed that ALT and AST levels were significantly reduced in A group (P < 0.05), none of the patients (0/27) suffered from acute liver injury, but 14.29% (5/35) patients in B group suffered from acute liver injury, and liver function could be recovered by substitution treatment of ademetionine (the median time is 8 days, 5-14 days). It is concluded that the protective and therapeutic effect of ademetionine against liver injury caused by chemotherapy in patients with leukemia is better than that of compound glycyrrhizin.

Analysis of clinical characteristics and prognosis of 13 cases of acute erythroleukemia / 中国实验血液学杂志

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.