Adult acute promyelocytic leukemia with thrombosis as the first manifestation: a clinical analysis of 6 cases / 中华全科医师杂志

The clinical data of 6 acute promyelocytic leukemia (APL) patients with thrombosis as the first manifestation were retrospectively analyzed. Among 6 patients, 5 were males and 1 female.The median age at diagnosis was 55 years old. All patients had risk factors for cardiovascular disease (CVD), and 5 patients met the diagnostic criteria for disseminated intravascular coagulation (DIC). There were 3 patients at low risk (bcr1 subtype), 1 at intermediate risk (bcr2 subtype) and 2 at high risk (1 bcr3 subtype and 1 unknown). FLT3-ITD mutations were tested in 3 cases, all of whom showed negative results. Arterial thrombosis was found in all 6 cases, 4 cases had cerebral infarction, 1 had lower limb arterial embolism, and 1 had multiple arterial and venous thrombosis. Four patients with cerebral infarction received all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO)±chemotherapy and symptomatic treatment (1 patient at high risk did not receive ATRA), 2 patients achieved complete remission (CR), and the other 2 patients died of cerebral hemorrhage and cerebral infarction, respectively. One patient with lower extremity arterial thrombosis died suddenly within 12 h after admission likely due to acute myocardial infarction. One patient with mixed thrombosis received low molecular weight heparin and rivaroxaban successively after inferior vena cava filter implantation, and achieved CR after ATRA+ATO treatment. Thrombosis is a less common and under-recognized presentation in APL.Thrombosis patients with blood cells and/or coagulation abnormalities should consider the possibility of APL. APL patients complicated with thrombosis have a high probability of DIC and remain mostly intractable to existing treatments, who are at high risk of death and poor prognosis.

A Leucemia Mieloide Aguda Poderia ter se Apresentado Ainda Pior? "Causa Incomum de Trombose Multiarterial Concomitante" / Could Acute Myeloid Leukemia Have Presented Even Worse? "Uncommon Cause of Concurrently Multivessel Thrombosis"

Resumo A leucemia promielocítica aguda (LPA) é um subgrupo da leucemia mieloide aguda (LMA). Embora se saiba que as complicações hemorrágicas são comuns, as complicações trombóticas não são tão raras quanto se pensa. No entanto, infarto do miocárdio e incidência de acidente vascular cerebral isquêmico são muito raros durante a LMA. Aqui, apresentamos o caso surpreendente de LPA diagnosticada com pancitopenia em sua apresentação com infarto agudo do miocárdio e acidente vascular cerebral isquêmico.

Abstract Acute promyelocytic leukemia (APL) is a subgroup of acute myeloid leukemia (AML). Although it is known that hemorrhagic complications are common, thrombotic complications are not as rare as thought. However, myocardial infarction and ischemic stroke incidence are very rare during AML. Here, we present the astonishing case of APL diagnosed with pancytopenia in its presentation with acute myocardial infarction and ischemic stroke.

Effects of interferon regulatory factor 9 on the biological phenotypes in PML-RARα-induced promyelocytic leukemia / 中华血液学杂志

Objective: To investigate the prognostic significance of interferon regulatory factor 9 (IRF9) expression and identify its role as a potential therapeutic target in acute promyelocytic leukemia (APL) . Methods: The gene expression profile and survival data applied in the bioinformatic analysis were obtained from The Cancer Genome Atlas and Beat acute myeloid leukemia (AML) cohorts. A dox-induced lentiviral system was used to induce the expression of PML-RARα (PR) in U937 cells, and the expression level of IRF9 in U937 cells treated with or without ATRA was examined. We then induced the expression of IRF9 in NB4, a promyelocytic leukemia cell line. In vitro studies focused on leukemic phenotypes triggered by IRF9 expression. Results: ①Bioinformatic analysis of the public database demonstrated the lowest expression of IRF9 in APL among all subtypes of AML, with lower expression associated with worse prognosis. ②We successfully established a PR-expression-inducible U937 cell line and found that IRF9 was downregulated by the PR fusion gene in APL, with undetectable expression in NB4 promyelocytic cells. ③An IRF9-inducible NB4 cell line was successfully established. The inducible expression of IRF9 promoted the differentiation of NB4 cells and had a synergistic effect with lower doses of ATRA. In addition, the inducible expression of IRF9 significantly reduced the colony formation capacity of NB4 cells. Conclusion: In this study, we found that the inducible expression of PR downregulates IRF9 and can be reversed by ATRA, suggesting a specific regulatory relationship between IRF9 and the PR fusion gene. The induction of IRF9 expression in NB4 cells can promote cell differentiation as well as reduce the colony forming ability of leukemia cells, implying an anti-leukemia effect for IRF9, which lays a biological foundation for IRF9 as a potential target for the treatment of APL.

Comparison of clinical efficacy and treatment costs in different regimens for patients with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective:To explore the clinical efficacy and treatment costs of different regimens for newly diagnosed acute promyelocytic leukemia (APL).Methods:The clinical data of 37 newly diagnosed APL patients admitted to Jingjiang People's Hospital from January 2011 to December 2020 were retrospectively analyzed. They received different induction therapy regimens and consolidation therapy after achieving complete remission (CR). Among them, 11 patients received induction chemo therapy with all-trans retinoic acid (ATRA) combined with anthracycline, which was consolidated with ATRA combined with chemotherapy after CR (ATRA+chemotherapy group); 13 patients were treated with ATRA combined with arsenite acid (ATO) and anthracycline, which was consolidated with ATRA combined with chemotherapy after CR(ATRA+ATO+ chemotherapy group). The other 13 patients received double induction therapy of ATRA combined with ATO, which was consolidated with ATRA combined with ATO after CR (ATRA+ATO double induction group). The clinical efficacy and treatment costs of newly diagnosed APL patients in 3 groups were analyzed.Results:There were 10, 12, 12 patients with newly diagnosed APL achieving CR, respectively in ATRA+chemotherapy group, ATRA+ATO+chemotherapy group, ATRA+ATO double induction group, and the difference was statistically significant ( P > 0.05). The differences of hematological, cardiac, gastrointestinal adverse reactions and infection incidence in the 3 groups were not statistically significant (all P > 0.05). The costs of induction therapy in ATRA+chemotherapy group, ATRA+ATO+chemotherapy group and ATRA+ATO double induction group were (73 755±4 820) yuan, (74 101±5 097) yuan, (52 944±4 099) yuan, respectively; the costs of consolidation treatment were (26 366±2 497) yuan, (25 801±2 528) yuan, (19 674±1 940) yuan, and the treatment time was (41±4) d, (39±4) d, (34±3) d, respectively; and the differences were statistically significant ( F value was 84.77, 31.90, 9.62, all P < 0.001). Conclusion:The chemotherapy-free therapy regimen of induction and consolidation with ATRA and ATO has the advantage of high cost-effectiveness with no significant difference in clinical efficacy.

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.

Leucemia promielocítica aguda. Estado del arte / Acute promyelocytic leukemia. State of the art

RESUMEN La leucemia promielocítica aguda (LPA) es un subtipo de leucemia mieloide aguda (LMA) que se origina por una traslocación balanceada entre los cromosomas 15 y 17, involucra al gen que codifica para el receptor alfa del ácido retinoico (RARA) en el cromosoma 17 y el de la leucemia promielocítica (PML) en el cromosoma 15, lo que da origen a la traslocación t(15;17) PML/RARA. Dicho reordenamiento origina la proteína de fusión PML/RAR alfa, que bloquea la diferenciación de las células madre mieloides en el estadio de promielocito. La LPA afecta con mayor frecuencia a adultos jóvenes y conlleva un alto riesgo de mortalidad temprana, en especial por el desarrollo de una coagulopatía grave, que sin tratamiento es definitivamente fatal. El diagnóstico temprano, el tratamiento de soporte y la introducción de fármacos que promueven la diferenciación terminal de los promielocitos patológicos como la tretinoina, también conocida como ácido todo transretinoico (ATRA) o trióxido de arsénico (ATO), ha hecho que en la actua-lidad esta sea una enfermedad curable con altas tasas de remisión completa.

SUMMARY Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) that results from a balanced translocation between chromosomes 15 and 17, which involves the gene encoding the retinoic acid receptor alpha (RARA) on chromosome 17 and the gene for promyelocytic leukemia (PML) on chromosome 15, causing the translocation t (15; 17) PML / RARA. This rearrangement originates the PML / RAR alpha fusion protein, which blocks the differentiation of myeloid stem cells at the promyelocyte stage. APL affects young adults more frequently and carries a high risk of early mortality, especially due to development of severe coagulopathy that, without treatment, is invariably fatal. Early diagnosis, supportive treatment, and the introduction of drugs that promote the terminal differentiation of pathological promyelocytes such as alltrans retinoic acid (ATRA) and arsenic trioxide (ATO), have currently made this a curable disease with high rates of complete remission.

Clinical efficacy of compound Huangdai tablets combined with all-trans retinoic acid in the treatment of acute promyelocytic leukemia / 中国基层医药

Objective:To investigate the clinical efficacy of compound Huangdai tablets combined with all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Methods:A total of 120 patients with acute promyelocytic leukemia who received treatment in the First People's Hospital of Huzhou, China between February 2013 and February 2015 were included in this study. They were randomly assigned to receive either all-trans retinoic acid, mercaptopurine and methotrexate in combination (control group, n = 60) or all-trans retinoic acid combined with compound Huangdai tablets (study group, n = 60). The time to hemoglobin rebounding, the time to platelet count rebounding, and the time to first complete remission were recorded. The recurrence and death of patients during 5 years of follow up were recorded. Adverse drug reactions during the treatment period were recorded. Results:The time to hemoglobin rebounding, the time to platelet count rebounding, and the time to first complete remission in the study group were (19.56 ± 2.61) days, (20.42 ± 2.73) days, (1.74 ± 0.45) months, respectively, which were significantly shorter than those in the control group [(28.42 ± 3.85) days, (30.63 ± 4.02) days, (3.31 ± 0.69) months, t = 10.328, 9.746, 8.521, P < 0.001]. The 1-year and 5-year recurrence rate in the study group were 11.37% and 21.67% respectively, which were significantly lower than those in the control group [28.33%, 41.67%, χ2 = 5.208, 5.546, P = 0.022, 0.019]. 5-year mortality rate in the study group was significantly lower than that in the control group [8.33% vs. 25.00%, χ2 = 6.000, P = 0.014]. There was no significant difference in adverse drug reaction between study and control group [28.33% vs. 26.67%, χ2 = 0.042, P = 0.838]. Conclusion:Compound Huangdai tablets combined with all-trans retinoic acid can effectively shorten the remission time of acute promyelocytic leukemia, reduces the disease recurrence rate and mortality rate, and is highly safe.

Myeloid sarcoma: an uncommon presentation of myeloid neoplasms; a case series of 4 rare cases reported in a tertiary care institute

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.

Detección del gen fusión PML-RARα en pacientes colombianos con leucemia mieloide aguda / Detection of the PML-RARα fusion gene in Colombian patients with acute myeloid leukemia

Resumen Introducción: la leucemia promielocítica aguda es un subtipo de leucemia mieloide aguda caracterizada por la presencia de una translocación entre los cromosomas 15 y 17 que provoca la formación de un gen fusión denominado PML/RARα. Determinar la presencia de este gen fusión es crítico para estos pacientes ya que su presencia hace el diagnóstico de la enfermedad, aún sin tener resultados de patología. Con esta investigación se busca ajustar e implementar una prueba altamente sensible y específica para la detección del reordenamiento PML/RARα. Métodos: a partir de sangre periférica se extrajo RNA de pacientes diagnosticados con leucemia mieloide aguda en dos instituciones de Antioquia (Colombia). Se realizó RT-PCR anidada para la detección de PML/RARα, ajustando un protocolo previamente publicado. Resultados: se ajustó y estandarizó un método para detectar mediante RT-PCR el gen fusión PML/RARα. Mediante esta técnica se logró identificar la traslocación en cuatro pacientes (22 %) de la cohorte estudiada. Conclusiones: los resultados están de acuerdo con estudios previos. La detección de esta y otras alteraciones citogenéticas mediante pruebas moleculares permitirá tener información valiosa a nivel de diagnóstico y pronóstico de los pacientes con leucemia mieloide aguda en Antioquia.

Abstract Introduction: acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the presence of a translocation between chromosomes 15 and 17, which causes the formation of a fusion gene called PML/RARα. Determining the presence of this fusion gene is critical for these patients, since their presence makes the diagnosis of the disease, even with no pathology results This research seeks to adjust and implement a highly sensitive and specific test for the diagnosis of this cytogenetic abnormality. Methods: peripheral blood samples from patients diagnosed with acute myelocytic leukemia were collected in two institutions of Antioquia (Colombia), from which RNA was extracted and nested RT-PCR was performed, adjusting a previously published protocol. Results: we adjusted and standardized a method to detect the PML/RARα fusion gene by RT-PCR. Using this technique, translocation was identified in four patients (22%) of the studied cohort. Conclusions: our results agree with previous studies. The detection of this and other cytogenetic alterations by means of molecular tests will allow to have valuable information at the level of diagnosis and prognosis of patients with AML in Antioquia.

Cytogenetic test and clinical study on cryptic acute promyelocytic leukemia with ins (15; 17) / 中华血液学杂志

Objective@#To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis.@*Methods@#From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results.@*Results@#A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy.@*Conclusion@#The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.

Comparison of the costs of different clinical treatment plans for children with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective@#To explore the costs and other information of two different treatment plans for pediatric acute promyelocytic leukemia (APL): one is the traditional intravenous drip arsenic (arsenic trioxide) combined with chemotherapy treatment, and the other is a medication family treatment program based on oral arsenic (Realgar-Indigo naturalis formula), in order to provide a reference for the promotion of pediatric APL family treatment mode and the formulation of medical insurance policies.@*Methods@#The medical record homepage data and drug using of pediatric APL from 2010 to 2018 in Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively analyzed, and the newly diagnosed pediatric patients (≤14 years old) with APL were included. The hospitalization expenses and hospitalization time of two treatment options were compared. One treatment option was Chinese children APL treatment plan 2010 (CCAPL 2010), which was based on intravenous drip arsenic trioxide. The other was Chinese Children Cancer Group APL treatment plan 2017 (CCCG-APL 2017), which was based on oral Realgar-Indigo naturalis formula.@*Results@#A total of 79 pediatric APL patients were included and grouped according to the treatment plans, 56 patients were treated with CCAPL 2010 plan, and 23 patients were treated with CCCG-APL 2017 plan. The median costs of one single pediatric APL patient in CCAPL 2010 plan was 167 700 yuan (95 800-386 600 yuan), and the median hospital stay time of one single pediatric APL patient was 102 days (14-157 days). The median costs of one single pediatric APL patient in CCCG-APL 2017 plan group was 118 700 yuan(50 800-270 600 yuan), and the median hospital stay time of one single pediatric APL patient was 37 days(5-96 days). The costs and hospital stay time of one single pediatric APL patient with CCCG-APL 2017 plan were remarkably less than those of one single pediatric APL patient with CCAPL 2010 plan (U = 178, P < 0.01; U = 66, P < 0.01).@*Conclusions@#The CCCG-APL 2017 plan simplifies the treatment plan compared with the CCAPL 2010 plan and significantly reduces the patient's medical expenses and shortens the hospitalization days. The CCCG-APL 2017 plan is suitable for family therapy and has good social and economic benefits, which is worthy of clinical promotion.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.

Therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia: a report of four cases and literature review / 中华血液学杂志

Objective@#To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) .@*Methods@#Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed.@*Results@#The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months.@*Conclusions@#Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.

Acute promyelocytic leukemia with t(2;17;15): report of one case and review of literature / 白血病·淋巴瘤

Objective@#To explore the clinical and laboratory characteristics and therapeutic effect of acute promyelocytic leukemia (APL) with t(2;17;15).@*Methods@#The G-banding technique was used for karyotypic analysis in a female patient with APL who was admitted to the First Affiliated Hospital of Zhengzhou University in December 2018. PML-RARα fusion gene was quickly detected by fluorescence in situ hybridization (FISH). The real-time quantitative polymerase chain reaction (RT-PCR) was used to detection 43 kinds of fusion gene, and the gene mutations were detected by next generation sequencing (NGS). The induction therapy was given with oral retinoic acid+ intravenous infusion of arsenic trioxide, followed by 3 courses of retinoic acid+ arsenic trioxide consolidation therapy.@*Results@#The G-banding karyotypic analysis demonstrated 46, XX, t(2;17;15) (q31;q21;q22)[8]/46, XX[2]. FISH results indicated that 62.0% of analyzed cells were positive for the PML-RARα fusion gene. RT-PCR further revealed the positive PML-RARα fusion gene transcript. NGS detection of gene mutations showed no obvious abnormalities. After 39 days of induction therapy with retinoic acid and arsenic trioxide, the patient achieved complete remission (CR). The karyotype was 46XX[20], and PML-RARα/ABL was 0/100. Then, the patient was treated with 3 courses of consolidation therapy, and the results remained in CR.@*Conclusions@#APL with complex t(2;17;15) (q31;q21;q22) is rare, and the morphological characteristics are not typical, but it is still associated with the formation of PML-RARα fusion gene. Retinoic acid+ arsenic trioxide has a good therapeutic effect, and the long-term efficacy still needs follow-up.

Clinical features of different isoforms of PML鄄RARα fusion gene in patients with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To explore the clinical features and prognosis of different PML_RARα fusion gene isoforms in acute promyelocytic leukemia (APL). Methods The clinical data of 78 patients initially diagnosed with APL in Fujian Medical University Union Hospital from February 2013 to July 2016 were collected. The clinical features and prognosis of different PML_RARα fusion gene isoforms were analyzed. Results There were 32 females (41%) and 46 males (59%) in 78 patients, with a median age of 40 years old (13-68 years old). The most common PML_RARα fusion gene was L type (48.7%, 38/78), followed by S type (46.2%, 36/78) and V type (5.1%, 4/78). The patients with white blood cell count more than 10×109/L (high_risk) occurred mostly in S type (61.1%, 22/36), compared with V type and L type, and there were statistically different (χ 2 ＝ 7.683, P < 0.05). A total of 78 patients included 8 cases (10.2%) of combined CD34 positive, 17 cases (21.8%) of combined FLT3_ITD mutation, 12 cases (15.4%) of combined DNMT3A mutation and 9 cases (11.5%) of additional chromosomal abnormalities. There were no significant differences in CD34 positive, FLT3_ITD, DNMT3A, and the incidence of additional chromosomal abnormalities among the three different isoforms (P＞0.05). The most common occurrence of retinoic acid syndrome (RAS) during treatment was S type (21/36), while rare for L type and V type (χ2＝ 7.633, P< 0.05). There were no statistical differences in the complete remission (CR) rate and disease_free survival rate among the patients with different PML_RARα isoforms (P＞0.05). Conclusions The clinical characteristics of different PML_RARα fusion gene isoforms are different, including most_common L type, more_common V type and S type in high risk groups; complicated RAS is commonly found in S type during the treatment. And different isoforms have no effect on the CR and DFS rate.

Acute promyelocytic leukemia with NPM鄄RARα fusion gene positive: report of one case and review of literature / 白血病·淋巴瘤

Objective To investigate the diagnosis, treatment and prognosis of acute promyelocytic leukemia (APL) with NPM_RARα fusion gene positive. Methods One APL patient with NPM_RARα fusion gene positive who was diagnosed by using morphology, immunology, cytogenetics, molecular biology and multiplex fluorescence in situ hybridization in Changhai Hospital in November 2014 was retrospectively analyzed, and the patient was induced with retinoic acid and treated with DA (daunorubicin + cytarabine) regimen, followed by 4 courses of cytarabine consolidation therapy. Results Abnormal promyelocyte accounted for 0.64 by morphology. And the group of cells expressed myeloperoxidase (MPO), CD13, CD15, CD117, and CD7, CD11c, CD79a, CD123 weakly expressed or not by immunophenotype analysis; karyotype analysis showed 45, XY, t(5;17), 7p-,-16[8]/46, idem,+20[5]/45, idem,-8,+20[2]/46, XY[5]; the fusion gene screening showed that the expression level of NPM_RARα was 416.98% compared with that of APL; molecular complete remission was obtained after the consolidation therapy, but the patient relapsed after 34 months. Finally, the patient died of abnormal coagulation and respiratory failure, with overall survival of 35 months. Conclusion APL with NPM_RARα fusion gene positive is a rare type of acute leukemia, and the main treatment method is retinoic acid combined with myeloid chemotherapy regimen, which has a favorable efficacy but a poor prognosis.

Effect of FMS﹣like tyrosine kinase 3 mutations on prognosis of acute promyelocytic leukemia: a Meta﹣analysis / 白血病·淋巴瘤

Objective To systematically evaluate the effect of FMS﹣like tyrosine kinase 3 (FLT3) mutations on prognosis of acute promyelocytic leukemia. Methods The databases of CNKI, Wanfang, VIP, China Biology Medicine disc, PubMed, EMBase, and Cochrane Library were retrieved, and the cohort studies and case﹣control studies published from the establishment of the databases to December 2017 were selected according to the inclusion and exclusion criteria. The quality assessment and data extraction was performed and the statistical analysis was performed by using RevMan 5.3 software. Results Twenty﹣three studies were included, covering a total of 2 632 patients. Meta﹣analysis showed that patients with FLT3 internal tandem duplication (FLT3﹣ITD) mutation had lower complete remission rate ( RR＝0.92, 95% CI 0.86-0.99, P＝0.02), 3﹣year overall survival rate ( RR＝0.72, 95% CI 0.60-0.88, P＝0.001) and 5﹣year overall survival rate ( RR＝0.89, 95% CI 0.81-0.99, P＝ 0.03), while the proportion of high﹣risk group ( RR＝ 3.13, 95% CI 2.26-4.35, P< 0.01), the early mortality rate ( RR＝ 2.26, 95% CI 1.75-2.90, P< 0.01) and the recurrence rate ( RR＝1.50, 95% CI 1.11-2.02, P＝0.008) were relatively high, and the differences were statistically significant. The patients with FLT3 tyrosine kinase domain (FLT3﹣TKD) mutation had higher early mortality rate ( RR＝ 3.00, 95% CI 1.74-5.20, P< 0.01), and the difference was statistically significant. Conclusion The FLT3 mutations can influence the prognosis of acute promyelocytic leukemia, which contributes to the research direction of better prognosis stratification, perfect treatment regimen and improved prognosis.

Comparison of the costs of different clinical treatment plans for children with acute promyelocytic leukemia / 白血病·淋巴瘤

Objective To explore the costs and other information of two different treatment plans for pediatric acute promyelocytic leukemia (APL): one is the traditional intravenous drip arsenic (arsenic trioxide) combined with chemotherapy treatment, and the other is a medication family treatment program based on oral arsenic (Realgar-Indigo naturalis formula), in order to provide a reference for the promotion of pediatric APL family treatment mode and the formulation of medical insurance policies. Methods The medical record homepage data and drug using of pediatric APL from 2010 to 2018 in Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively analyzed, and the newly diagnosed pediatric patients (≤14 years old) with APL were included. The hospitalization expenses and hospitalization time of two treatment options were compared. One treatment option was Chinese children APL treatment plan 2010 (CCAPL 2010), which was based on intravenous drip arsenic trioxide. The other was Chinese Children Cancer Group APL treatment plan 2017 (CCCG-APL 2017), which was based on oral Realgar-Indigo naturalis formula. Results A total of 79 pediatric APL patients were included and grouped according to the treatment plans, 56 patients were treated with CCAPL 2010 plan, and 23 patients were treated with CCCG-APL 2017 plan. The median costs of one single pediatric APL patient in CCAPL 2010 plan was 167 700 yuan (95 800-386 600 yuan), and the median hospital stay time of one single pediatric APL patient was 102 days (14-157 days). The median costs of one single pediatric APL patient in CCCG-APL 2017 plan group was 118 700 yuan(50 800-270 600 yuan), and the median hospital stay time of one single pediatric APL patient was 37 days (5-96 days). The costs and hospital stay time of one single pediatric APL patient with CCCG-APL 2017 plan were remarkably less than those of one single pediatric APL patient with CCAPL 2010 plan (U ＝ 178, P < 0.01; U ＝ 66, P< 0.01). Conclusions The CCCG-APL 2017 plan simplifies the treatment plan compared with the CCAPL 2010 plan and significantly reduces the patient's medical expenses and shortens the hospitalization days. The CCCG-APL 2017 plan is suitable for family therapy and has good social and economic benefits, which is worthy of clinical promotion.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.

Application of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia / 中华血液学杂志

Objective@#To investigate the application values of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia (APL) .@*Methods@#The retrospective analyses of flow cytometric (FCM) immunophenotypic anyalysis, chromosome karyotype and chromosome fluorescence in situ hybridization (FISH) of 798 outpatient or hospitalization APL patients referred to our hospital between May 2012 and December 2017 were performed to further study the application values of FCM and molecular genetics in the diagnosis of APL.@*Results@#The sensitivity and specificity of FCM were 91.9% and 98.7% respectively. The typical characteristic immunophenotype for APL was as of follows: a high SSC, absence of expression of cluster differntiation (CD) CD34 and HLA-DR, and expression or stronger expression of CD33, consistent expression of CD13, CD9, CD123, expression of CD56, CD7, CD2 (sometimes) . The rest 10% of the cases harbored atypical APL phenotypes, generally accompanied by CD34 and/or HLA-DR expression, decreased SSC and often accompanied by CD2 expression, it was difficult to definitively diagnose APL by this FCM phenotype, and their diagnoses depended on the results of genetics or molecular biology tests. Compared with normal individuals, complex karyotypes APL with t (15;17) translocation, other variant translocations and variant t (11;17) , t (5;17) had no significant differences in terms of their FCM phenotypes.@*Conclusions@#FCM could rapidly and effectively diagnose APL. Despite the fact that complex karyotypes with various additional chromosomal abnormalities were detected in approximately one third of APL cases in addition to the pathognomonic t (15;17) (q22;q21) , they had no observable impact on the overall immunophenotype. Molecular and genetic criteria were the golden criteria for the diagnosis of APL. About 10% of immunophenotyping cases relied on molecular genetics for diagnosis.