Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases / 中华血液学杂志

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

Efficacy of Arsenic Trioxide Combined with ATRA and Chemotherapy for Relapsed Acute Promyelocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients.@*METHODS@#The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed.@*RESULTS@#Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications.@*CONCLUSION@#For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

Clinical Features and Therapeutic Efficacy in Adult Acute Lymphoblastic Leukemia with t (1; 19) (E2A-PBX1) / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1).@*METHODS@#The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed.@*RESULTS@#In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166).@*CONCLUSION@#Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.

Clinical Characteristics of Patients with Ph Mixed Phenotype Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical biological characteristics and prognosis of the patients with mixed phenotype acute leukemia with t(9;22)(q34;q11.2) and/or BCRABL1 (Ph MPAL).@*METHODS@#The morphological, immunological, cytogenetic, and molecular features of 33 in patients with Ph MPAL were retrospectively analyzed in our center from June 2002 to June 2016 according to the scoring proposal of European Group for the Classification of Acute Leukemia(EGIL )1998 and WHO 2008 criteria. All the cases were either treated with acute lymphoblastic leukemia (ALL) induction regimen or combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia,part of which also received tyrosine kinase inhibitor(TKI) and 5 cases underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission.@*RESULTS@#Ph MPAL occurred predominantly in male patients (ratio of M/F was 1.75∶1), and a high WBC counts at diagnosis; the WBC count was higher than 30×10/L in 25 patients( 75.8% )， and appeared higher than 100 ×10/L in 13 patients ( 39.4%). Among all the 33 PhMPAL patients, 32 (97.0%) had a myeloid / B-lymphoid (M/B) phenotype， and 1 case(3.0%) had a myeloid/ B-lymphoid/ T-lymphoid/ (M/B/T) phenotype. There was no patients displayed myeloid / T-lymphoid (M/T) or B-lymphoid/ T-lymphoid/ (B/T) phenotype. 19 of all cases(57.6%) met the diagnosis criteria of PhMPAL based on EGIL 1998 criteria, while the remaining 14 cases can be diagnosed as Ph MPAL by WHO 2008 classification,but excluded as PhMAPL by EGIL 1998.Karyotype analysis was successfully performed in 31 cases, and out of them 13 (41.9%) had a sole Ph chromosome, 10 (32.3%) had additional chromosome aberration and Ph chromosome was not found in 8 cases (25.8%) .In 31 patients the fusion gene BCR/ABL (P190、P210) was detected,including 17 (54.8%) cases with the p190 BCR/ABL transcript, 8 (25.8%) cases with the p210 BCR/ABL transcript, 4 (12.9%) expressing both transcripts and 2 (6.5%) without any one of these 2 transcripts. 24 out of 33 patients (77.4%) achieved complete remission after induction therapy. The median time achieving CR was 43(26-98)days. The CR rate of patients treated with and without imatinib after the first inducion treatment was 81.3% and 46.7%,respectively (P0.05). Within the 17 patients treated with imatinib at induction stage，2 of which became BCR/ABLnegative．At consolidation chemotherapy stage, 9 out of 16 patients became BCR/ABL negative, including 3 patients already subjected to HSCT. The median time reached to BCR/ABL negative was 2.87（1.13-9.20）months.@*CONCLUSION@#Ph MPAL is more common in male, and inclined to high WBC counts at diagnosis. Myeloid/B lymphoid phenotype is more common, and the prognosis of patients with PhMPAL is poor. Imatinib and allogeneic hematopoietic stem cell transplantation may improve survival of patients with PhMPAL.

Values of Procalcitonin for Predicting Outcome of Infection in Acute Leukemia Patients with Bacterial Bloodstream Infection / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of serum procalcitonin(PCT) levels for predicting the outcome of bacteria bloodstream infection in acute leukemia patients.</p><p><b>METHODS</b>Clinical data from 236 patients with acute leukemia accompanied by bacterial bloodstream infection during July 2014 to November 2017 were retrospectively analyzed, 236 patients were divided into 5 groups (<0.05 ng/ml, 0.05- <0.5 ng/ml, 0.5- <2.0 ng/ml, 2.0- <10.0 ng/ml and >10.0 ng/ml) according to PCT concentrations.</p><p><b>RESULTS</b>The median age of patients was 40(13-73) years old. The male 123 cases(52.1%) and female 113 cases(47.9%) in 236 patients. The incidence of infection-related dealth in 5 groups was 0%, 1.4%, 13.8%, 25.0% and 33.3%, respectively; the incidence of septic shock and other serious complications in 5 groups was 0%, 2.1%, 13.8%, 25.0%, 33.3% and 6.4%, 7.0%, 24.1%, 41.7%, 50.0%, respectively, showing the concentration dependent manner and statistically significant difference (u=2127, P=0.000; u=2234, P=0.000; u=4102, P=0.000). Further analysis showed that with the increase of PCT concentration, the cumulative incidence of septic shock, infection-related death and other serious complications was gradually increased with statistically significance (HR=2.887, P=0.000, 95%CI:1.960-4.260; HR=3.158, P=0.000, 95%CI: 2.100-4.740; HR=2.158, P=0.000, 95%CI:1.550-3.000) respectively. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death (HR=2.517, P=0.000, 95%CI: 1.520-4.168; HR=2.881, P=0.000, 95%CI: 1.692-4.904)respectively.</p><p><b>CONCLUSION</b>Serum procalcitonin level positively correlates with the incidence of serious bacteria bloodstream infection complications in the patients with acute leukemia. Increased procalcitonin level is an independent risk factor for septic shock and infection-related death, indicating that procalcitonin may be an important prognostic factor for infection outcome in acute leukemia patients with bacteremia.</p>

Primary Prophylatic Effect of Voriconazole Against Invasive Infection of Pulmonary Aspergillosis during Remission-Induction Chemotherapy for Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of primary prophylaxis of voriconazole against invasive infection of pulmonary aspergillosis (IPA) during remission-induction chemotherapy (RIC) of patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>Clinical data of 102 de novo AML patients who received primary anti-IPA prophylaxis during the first induction chemotherapy were analyzed retrospectively. All the cases were divided into voriconazole-treated group and posaconazole-treated group according to the prophylactic agent. The incidences of IPA and systemic antifungal treatment during induction chemotherapy were analyzed for both groups.</p><p><b>RESULTS</b>Among 102 enrolled cases, 42 cases received voriconazole and other 60 received posaconazole as primary prophylaxis. IPA occurred in 3 cases of voriconazole group (1 probable, 2 possible); IPA occurred in 4 cases of posaconazose group, and all were possible cases. The incidence of IPA during remission-induction chemotherapy in variconazole group equaled to posaconazose group (7.1% vs. 6.7%) (P=0.925). Beside IPA cases, 2 cases in voriconazole group and 4 cases in posaconazole group received intravenous anti aspergillosis drugs preemptive treatment, and no significant difference of prophylactic success rate was observed between two groups (88.1% vs. 86.7%) (P=0.831). Visual disturbance was the most common adverse event occurred in voriconazole group, but no significant differences of incidences of other adverse effects were observed when compared with posaconazole group.</p><p><b>CONCLUSION</b>According to similar prophylactic effect with posaconazole, voriconazole appears to be a good alternative for primary prophylaxis of IPA during remission-induction chemotherapy in AML patients.</p>

FLT3-ITD Mutation in Newly Diagnosed Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the influence of FLT3-ITD mutation on long term survival of newly diagnosed patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Long term survival of 170 newly diagnosed APL patients was retrospective analyzed. Mutation rate of FLT3-ITD was assayed, and its influence on disease-free survival(DFS) or overall survival (OS) was analyzed.</p><p><b>RESULTS</b>The mutation rate of FLT3-ITD in newly diagnosed patients with APL was 14.1%. WBC count at diagnosis was higer in FLT3-ITD positive group than that in negative group, and the mutation rate of FLT3-ITD was highest in high risk group. Induction death rate in FLT3-ITD positive and negative group were 12.5% and 2.9%, respectively (P=0.031). Complete remission(CR) rate in 2 groups were 83.3% and 97.1%(P=0.004). The 5-year OS rates in 2 groups were 87.5±6.8% and 90.6±2.6% (P=0.740). The 5-year DFS in 2 groups were 82.8±9.1% and 83.6±3.4%(P=0.928).</p><p><b>CONCLUSION</b>FLT3-ITD mutation is related with high peripheral white blood cell count in APL, the APL with FLT3-ITD mutation has higher induction death rate and lower CR rate than those in that without FLT3-ITD mutation, but FLT3-ITD mutation did not affect on long term DFS and OS.</p>

Analysis of tumor lysis syndrome in 380 cases of acute leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This studay was aimed to explore the incidence and risk factors of tumor lysis syndrome (TLS) in patients with acute leukemia.</p><p><b>METHODS</b>A tatol of 380 patients who were newly diagnosed as acute leukemia and received combination chemotherapy were retrospectively analyzed. The TLS was diagnosed according to criteria of Cario and Bioshop, the risk factors were evaluated on basis of examination results.</p><p><b>RESULTS</b>The tumor lysis syndrome occurred in 20.8% (79/380) of patients, out of them the clinical TLS was 0.5% (2/380), laboratorial TLS was 20.3% (77/380). The unvariate analysis showed that male, high WBC count, hepatomegaly, splenomegaly, lympha-denoctasis, elevated AST, high creatinine, high uric acid level, high serum lactate dehydrogenase (LDH) level, or renal insufficiency were independent risk factors for TLS.</p><p><b>CONCLUSION</b>The TLS is a clinically common complication in patients with leukemia, especially during induction chemotherapy, therefore, for AL patients with high risk factors the TLS should be closely monitored, prevented and given better therapy.</p>

Characteristics of karyotypes and gene mutations for elder acute myeloid leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of karyotypes and gene mutations for elder acute myeloid leukemia and to explore the relationship between each other.</p><p><b>METHODS</b>Clinical data and bone marrow samples of elder AML patients were collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPα, DNMT3A) test were performed, characteristics of karyotypes and gene mutations were analysed.</p><p><b>RESULTS</b>The incidence of better risk karyotype was 16.6%, in which the incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and 1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in which the incidence of normal karyotype was 57.86%; the incidence of poor risk karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of FLT3, NPM1, C-Kit, CEBPα, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%, 15.71% respectively. Compared with patients older than 60 years, patients with age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003) and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs 5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045).</p><p><b>CONCLUSION</b>For older AML patients, great difference in the distribution of karyotyes was found between the patients older than 60 years and patients with age of 55-60 years, while no such characteristics was found for gene mutations. Good elucidation of karyotypes and gene mutations are key for the treatment of older acute myeloid leukemia patients.</p>

Efficacy Analysis of MAC Regimen as Salvage Treatment Protocol for Acute Myeloid Leukemia Patients Older Than 55 Years / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of MAC regimen in the treatment of acute myeloid leukemia(AML) patients older than 55 years.</p><p><b>METHODS</b>A total of 33 relapsed or non-remission AML patients older than 55 years were enrolled in this research. MAC regimen was given as the salvage treatment. Complete remission rate(CR), partial remission rate(PR), overall survival(OS), relapse-free survival(RFS) and adverse effect were analysed.</p><p><b>RESULTS</b>CR rate after the salvage therapy with MAC was 51.1%, partial remission (PR) rate was 6.1%, the overall response rate (ORR) was 57.6%, the median OS was 8 months (1.0-66.0 months), the median relapse-free survival (RFS) was 10.1 months (2.3-40.4 months). Mortality related with salvage treatment in 30 days was 9.1%. Low incidence of severe organ damage were found.</p><p><b>CONCLUSION</b>MAC can be used as a relative effective and safe regimen for the salvage treatment of the older AML patients.</p>

Clinical and laboratory features of acute monocytic leukemia with B lymphoproliferative disorders / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the clinical and pathological features of acute myeloid leukemia with B lymphoproliferative disorders.</p><p><b>METHODS</b>The characteristics of 3 cases of acute monocytic leukemia with untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis were reported with literatures review.</p><p><b>RESULTS</b>The patients presented with a history of anemia, bleeding and/or fever. Acute monocytic leukemia was diagnosed by bone marrow morphology, cytochemistry and pathology studies. Immunophenotyping by flow cytometry analysis showed a significant population of absolute B-lymphocyte count of > 5×10(9)/L in a patients, similar to that of chronic lymphocytic leukemia.</p><p><b>CONCLUSIONS</b>The association of acute monocytic leukemia and untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis was a rare event. The abnormal B lymphocytes was likely to be misdiagnosis. Thus, it was important to combine several kinds of laboratory studies, especially flow cytometry to identify this rare disorder.</p>

Sorafenib in combination with chemotherapy in the induction therapy for FLT3-ITD positive acute monocytic leukemia: a case report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the safety and efficacy of sorafenib in combination with chemotherapy for the treatment of FLT3 positive acute myeloid leukemia (AML), to highlight the impact of FLT3 mutations and targeting therapy on response of AML.</p><p><b>METHODS</b>The clinical and laboratory features and the treatment response, especially the safety profile of sorafenib in an acute monocytic leukemia patient with FLT-ITD were reported.</p><p><b>RESULTS</b>The patient achieved clinical and molecular CR after sorafenib was added to the second course of combination chemotherapy. The side effects of sorafenib were mild and tolerable.</p><p><b>CONCLUSION</b>The patient responded well to the combination of sorafenib and standard chemotherapy of AML without significant adverse effects.</p>

Analysis of effectiveness and prognostic factors for (m)HAD regimen as induction therapy in acute monocytic leukaemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the treatment outcome and impact of cytogenetic abnormalities on the response and survival of acute monocytic leukaemia (AMOL) patients received (m)HAD regimen as induction chemotherapy.</p><p><b>METHODS</b>Seventy-nine AMOL patients were treated with (m)HAD regimen as induction therapy (HHT 2 mg/m(2), d 1-7; Ara-C 100 mg/m(2), d 1-7 and increasing to 1.5 g×m(-2)×(12 h)(-1), d 5-7 in some patients; DNR 40 mg/m(2), d 1-3). The treatment outcome and prognostic factors were analyzed.</p><p><b>RESULTS</b>(1) The complete remission (CR) rate was 79.7% (63/79), partial remission (PR) rate was 6.3% (5/79), overall rate was 86.0%. (2) The chromosome karyotypes were analyzed in 75 patients, of whom 43 with normal karyotypes (NCR) and 30 abnormal karyotypes (ACR). For the cytogenetic prognostic groups, 49 patients were intermediate, 18 poor and 6 unknown. The CR, 1-year and 3-year overal survival (OS) rates in NCR group were significantly higher than those in ACR group (P < 0.05); but there was no significantly statistical difference in disease free survival (DFS) between the two groups (P > 0.05). The CR, 1-year OS, 3-year OS and 1-year DFS and 3-year DFS rates in intermediate prognostic group were significantly higher than those in poor prognostic group (85.7% vs 61.1%, 75.9% vs 51.3%, 65.4% vs 25.6%, 82.2% vs 66.7%, and 77.9% vs 26.7%, respectively) (P < 0.05). (3) Chromosome karyotype and the number of consolidation therapy courses had more important influence on survival in COX analysis.</p><p><b>CONCLUSION</b>(m)HAD regimen as induction chemotherapy for AMOL patients achieves a high CR rate. It has an important influence on survival for the patients to received adequate consolidation therapy. The frequency of cytogenetic abnormalities in AMOL is similar to that in other AMLs. The prognosis of AMOL patients with chromosome karyotype in intermediate prognostic group is significantly better than that in poor prognostic group.</p>

Outcome of acute promyelocytic leukemia with homoharringtonine (HHT) and ATRA / 中华血液学杂志

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>115 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Our study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.</p>

Cyclosporine A in combination with thalidomide for the treatment of patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficiency and side-effects of the combination of cyclosporine A (CsA) and thalidomide in patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>A total of thirty-seven patients with MDS-RCMD or-RAEB-I were treated with CsA in combination with thalidomide. The initial CsA dose of 3 mg×kg(-1)×d(-1) was administered, all patients had their CsA blood concentration concurrently monitored until it reached and maintained between 100 and 200 µg/L. The initial dose of thalidomide was 50 mg/d, with increasing dose of 50 mg every week until the maximum of 200 mg/d. The hematological response was assessed according to the modified criteria of the International Working Group, and adverse events were graded with the Common Toxicity Criteria (v3.0) of the National Cancer Institute. The response duration and overall survival of the patients were also observed.</p><p><b>RESULTS</b>19/37 cases (51.4%) achieved hematologic improvement (HI)-erythroid response (HI-E), 9/29 cases (31.0%) HI-platelet response (HI-P) and 7/33 cases (21.2%) HI-neutrophil response (HI-N). 15 of 32 transfusion-dependent patients (46.9%) achieved transfusion independence. The median response duration of HI-E, HI-P and HI-N were 88 (4 - 88) weeks, 78 (8 - 84(+)) weeks and 78 (10 - 84(+)) weeks respectively. The median overall survival was 52 months on a 29 (4 - 103) months median follow-up. Some patients developed grades I-II hepatic or nephritic impairment, constipation, lethargy, dizziness, edema, rashes or numbness, and all were tolerable and reversible. No grade III or severer adverse events were observed.</p><p><b>CONCLUSION</b>CsA in combination with thalidomide appears to be effective mainly in inducing HI-E and relatively well-tolerated for the treatment of patients with MDS.</p>

Acute promyelocytic leukemia with CD59 deficiency / 中国实验血液学杂志

CD59 is a glycosyl-phosphatidyl inositol-anchored protein with the capacity to block the formation of membrane-attack complex, and protect the cells from complement-mediated cytolysis. The study was aimed to investigate whether CD59 is deficient in acute promyelocytic leukemia (APL) blast cells. Expression of CD59 on APL blast cells was analysed by flow cytometry. Expression of CD59 on NB4 cells was determined by flow cytometry before and after treating with all trans retinoic acid (ATRA). Pig-A gene coding region was sequenced. The results showed that the deficiency of CD59 expression in 12 out of 19 APL samples was found, its incidence was significantly higher than that in other acute myeloid leukemia (AML) samples (deficiency of CD59 expression in 14 of 40 non-APL AML samples, p=0.042). The expression of CD59 became normal after the patients achieved complete remission (CR), which indicated that the deficient of CD59 expression was only found in APL blast cells, but also found in APL cell line NB4 cells. The expression of CD59 was not changed after NB4 cells were induced to differentiate by ATRA. Sequencing pig-A gene coding region of NB4 cells and one APL patient with deficiency of CD59 displayed that the mutation of pig-A gene was not observed, therefore the deficiency of CD59 expression in APL cells did not result from mutation of pig-A gene. It is concluded that the deficiency of CD59 expression exists in APL blast cells more probably.