Does leukocytosis remain a predictive factor for survival outcomes in patients with acute promyelocytic leukemia receiving ATRA plus a chemotherapy-based regimen? A prospective multicenter analysis from TALWG.

INTRODUCTION: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique clinical presentation and prognosis. This study aimed to investigate the epidemiology, clinical characteristics, treatments, and clinical outcomes of Thai APL patients dominantly treated with all-trans-retinoic acid (ATRA) combined with a chemotherapy-based therapy. METHODS: This was an eight-year prospective, observational study from nine academic hospitals in the Thai Acute Leukemia Working Group (TALWG) of the Thai Society of Hematology, which included newly diagnosed Thai APL patients, aged 18 years or older. The web-based registration collected baseline charateristic, and clinical outcomes. RESULTS: From 992 newly diagnosed AML patients, 79 APL patients were enrolled in this study. Almost all subjects were de novo APL (94.9%), while the others were therapy-related APL. The commonest clinical presentation was disseminated intravascular coagulation (38%). One-third of the patients were categorized as high risk according to the initial WBC. Almost all patients received ATRA combined with idarubicin regimen. The complete response rate was as high as 95.7%, which translated into excellent four-year overall survival (OS) (75.6%) and four-year leukemia-free survival (LFS) (75.4%). The multivariate analysis demonstrated that the older age and WBC count >20 × 109/L conferred a significantly unfavorable OS with the hazard ratios of 3.03 (95% confidence interval [CI]: 1.14-8.05) and 4.18 (95%CI: 1.69-10.35), respectively. Similarly, these two parameters remained independent of the poor prognosis factors for LFS. CONCLUSION: This report confirmed that APL had a favorable prognosis. However, advanced age and high WBC count >20 × 109/L contributed to a worse outcome. ABBREVIATIONS: APL; acute promyelocytic leukemia; ATRA; all-transretinoic acid; CR; complete remission; DS; differentiation syndrome; ECOG; Eastern Cooperative Oncology Group; ED; early death; HR; hazard ratio; IQR; interquartile range; LFS; leukemia-free survival; OS; overall survival; WBC; white blood cell.

Dengue virus infection in a patient with chronic myeloid leukemia.

This is a case report of a patient with chronic myeloid leukemia (CML) undergoing imatinib treatment who became infected with dengue virus. The patient presented with classic dengue symptoms, along with early minor bleeding (blood-stained sputum) during the first 5 days of illness. Continuous inpatient imatinib treatment for CML was given without blood transfusion. The hemoglobin and white blood-cell count slowly improved over 30 days while recovering from the dengue viral infection. The patient recovered from the dengue virus infection without complication. Clinical monitoring of hematologic changes is needed in dengue patients undergoing anticancer treatment.

Comparison of Three Doses of Cytarabine Consolidation for Intermediate- and Adverse-risk Acute Myeloid Leukemia: Real World Evidence From Thai Acute Myeloid Leukemia Registry.

BACKGROUND: Intermediate or high doses of cytarabine (IDAC or HiDAC) were recommended as postremission chemotherapy for acute myeloid leukemia (AML). This retrospective study investigated the real-world outcomes of 3-different cytarabine doses from the multicenter Thai AML registry database. PATIENTS AND METHODS: The intermediate- and adverse-risk AML patients (N = 258) who achieved complete remission and proceeded to single-agent cytarabine consolidation were enrolled. RESULTS: The median relapse-free survival (RFS) using IDAC 1.5 g/m2, high-dose cytarabine (HiDAC) 2 g/m2, and HiDAC 3 g/m2 were 12.6, 11.7, and 13 months, respectively. The median overall survival (OS) using IDAC 1.5 g/m2, HiDAC 2 g/m2, and HiDAC 3 g/m2 were 34.9, 22.7, and 23.7 months, respectively. No significant difference in RFS and OS was detected between the 3 doses. Secondary AML, white blood cell > 100×109/L and the adverse-risk AML were independent prognostic factors for inferior survival (P= .008, P < .001, P= .014). Patients who completed 3 to 4 cycles of consolidation had significantly superior RFS and OS (P< .001, P< .001). Febrile neutropenia occurred in 72.9% of IDAC, 73.8% of HiDAC 2 g/m2, and 78.1% of HiDAC 3 g/m2 without statistical significance. However, the incidence of septic shock was significantly higher after HiDAC 3 g/m2 compared to IDAC regimen (8% vs. 3%, P= .037). CONCLUSION: IDAC is an appropriate regimen for postremission chemotherapy for intermediate- and adverse-risk AML. The higher dosing levels may not produce any benefits to patients and may increase incidence of septic shock. The number of consolidation cycles may impact on survivals rather than the intensity of cytarabine.

Characteristics and Outcomes of Secondary Acute Myeloid Leukemia and Acute Myeloid Leukemia With Myelodysplasia-Related Changes: Multicenter Study From the Thai Acute Leukemia Study Group.

BACKGROUND: Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) both result in dismal outcomes. This retrospective study aimed to determine whether these features are poor prognostic factors independent of older age and adverse cytogenetics, which are commonly associated with a poor prognosis. METHODS: The characteristics and real-world outcomes of sAML and AML-MRC from the Thai AML registry database were investigated. RESULTS: From a total of 992 newly diagnosed AML patients, 315 (31.8%) patients were classified into sAML or AML-MRC subtypes. Older age, low white blood cell (WBC) count, low bone marrow blast, and adverse cytogenetic risk were commonly present in sAML and AML-MRC compared to de novo AML. Complete remission after 7 + 3 induction therapy occurred in 42.3% of patients with sAML or AML-MRC and 62.4% of de novo AML (P < .001). The median overall survival (OS) of sAML, AML-MRC, and de novo AML were 6.9, 7.0, and 12.2 months, respectively (P < .001). The independent prognostic factors for inferior OS were older age, intermediate-risk or adverse-risk cytogenetics, WBC count > 100 × 109/L, poor performance status, and a subgroup of AML-MRC with the morphologic criteria of multilineage dysplasia (AML-MRC-M). In addition, sAML, AML-MRC, and a WBC count > 100 × 109/L were pre-treatment prognostic factors associated with poor relapse-free survival (P = .006, P = .017, and P < .001, respectively). CONCLUSION: Both sAML and AML-MRC are independently associated with poor outcomes in Thai patients. Our study supports AML-MRC-M as an adverse prognostic factor for OS.

False-Positive Nonstructural Protein 1 Antigen in a Patient with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Case Report with Literature Review.

BACKGROUND A rapid investigation of dengue viral infection is needed for physicians who manage patients with suspected dengue infection. The nonstructural protein 1 (NS1) test kit is commonly used to diagnose patients with acute febrile illness in dengue-endemic countries, although this test kit can yield false-positive results. The Dengue NS1 test kit mostly relies on cross-reaction among febrile illness patients with other viral infections rather than malignancies. CASE REPORT A 52-year-old male patient presented with 3 days of fever, intermittent gum bleeding, weight loss, and mucocutaneous bleeding. He was transferred to a second hospital with acute febrile illness. Both dengue NS1 antigen test kits were positive from the 2 hospitals where he was previously treated. Fever and cytopenia persisted, and then the dengue RT-PCR test was performed to establish the cause of illness. A peripheral blood smear was reviewed and showed blast cells. A bone marrow examination was done to test for the compatibility of lymphoblastic leukemia. The flow cytometry test showed B cells ALL with Philadelphia-positive chromosome. Finally, the result of the dengue RT-PCR test was negative. CONCLUSIONS Our patient presented with fever and viral-like illness, but he was finally diagnosed with Ph+ ALL. We demonstrated the first case of false-positive dengue NS1 antigen in a Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patient. Moreover, we reviewed the literature to gather information on false-positive results using the dengue NS1 test kit. The dengue NS1 test kit is useful and produces reliable clinical findings, especially in patients with hematological malignancies.

Atypical complication in an adult patient with dengue and autoimmune hemolytic anemia: a case report.

Severe dengue infection is associated with life-threatening complications, including severe bleeding. The bleeding tendency is typically associated with the shock phase of infection, for which blood replacement may be needed. However, repetitive blood transfusion can lead to volume overload. Administration of recombinant activated factor VII (rFVIIa) might be used to counteract bleeding without inducing volume overload. We describe the case of a patient with severe dengue infection who presented with intractable bleeding; he was initially treated with massive blood transfusions, which resulted in volume overload. He was then treated with rFVIIa to reverse the bleeding. During the second week of his hospitalization, his hematocrit dropped precipitously, and autoimmune hemolytic anemia was diagnosed. Supportive treatment was provided until recovery. Autoimmune hemolytic anemia is a rare complication in adult patients with dengue. Supportive care was effective for this atypical complication.

Machine Learning-Driven and Smartphone-Based Fluorescence Detection for CRISPR Diagnostic of SARS-CoV-2.

Rapid, accurate, and low-cost detection of SARS-CoV-2 is crucial to contain the transmission of COVID-19. Here, we present a cost-effective smartphone-based device coupled with machine learning-driven software that evaluates the fluorescence signals of the CRISPR diagnostic of SARS-CoV-2. The device consists of a three-dimensional (3D)-printed housing and low-cost optic components that allow excitation of fluorescent reporters and selective transmission of the fluorescence emission to a smartphone. Custom software equipped with a binary classification model has been developed to quantify the acquired fluorescence images and determine the presence of the virus. Our detection system has a limit of detection (LoD) of 6.25 RNA copies/µL on laboratory samples and produces a test accuracy of 95% and sensitivity of 97% on 96 nasopharyngeal swab samples with transmissible viral loads. Our quantitative fluorescence score shows a strong correlation with the quantitative reverse transcription polymerase chain reaction (RT-qPCR) Ct values, offering valuable information of the viral load and, therefore, presenting an important advantage over nonquantitative readouts.

Types, Clinical Features, and Survival Outcomes of Patients with Acute Myeloid Leukemia in Thailand: A 3-Year Prospective Multicenter Study from the Thai Acute Leukemia Study Group (TALSG).

BACKGROUND: Acute myeloid leukemia (AML) is a common, challenging hematologic malignancy worldwide. Thai data on its characteristics and outcomes have never been systematically reported, to our knowledge. The objective of this study was to determine the clinical features and outcomes of Thai patients with AML. PATIENTS AND METHODS: This was a prospective observational study of nine academic hospitals. Patients with newly diagnosed AML were invited to register online. RESULTS: A total of 679 patients with AML were included. The presence of circulating peripheral blood blasts was correlated with a high white blood cell count. Acute promyelocytic leukemia (APL) had predominantly lower white blood cell counts and higher proportions without peripheral blood blasts compared with non-APL AML. Disseminated intravascular coagulation was commonly presented in APL (37.7%). Splenomegaly and normal platelet count were more frequently seen in patients with Philadelphia chromosome-positive AML. The median follow-up time for those who survived more than 1 year was 28.0 months. One-year overall survival rates for non-APL AML and APL were 31.9% and 88.2%, respectively; 2-year overall survival rates were 29.6% and 88.2%, respectively. Hematopoietic stem cell transplantation could improve survival in non-APL AML. CONCLUSION: APL should be considered despite absence of peripheral blood blast. This study demonstrates poor outcome of Thai AML and more research to improve outcomes are underway. Expanding access to hematopoietic stem cell transplantation should be considered in Thailand.

False-positive dengue IgM test result in a patient with systemic lupus erythematosus: a case report.

Dengue virus infection most commonly has mild-to-moderate nonspecific clinical presentations that overlap with other diseases. Dengue-specific tests are commonly used for those patients with acute febrile illness in dengue-endemic areas. There is one study in vitro that showed a false-positive dengue-immunoglobulin M (dengue IgM) test for blood from a patient with systemic lupus erythematosus (SLE). Here, we demonstrated a false-positive dengue IgM test in a patient with SLE. The patient had fever, cytopenia, and a skin rash, but her clinical variables more closely matched with the criteria for SLE than the dengue infection. Vasculitis-like-lesions supported prednisolone administration and her clinical symptoms improved. This case highlights that some patients with SLE can be misdiagnosed as having a viral infection. These two diseases have similar clinical findings, such as acute febrile illness, but they are different in terms of their treatments and disease prognosis.

Improved Survival of Elderly-fit Patients With Acute Myeloid Leukemia Requiring Intensive Therapy: 3-Year Multicenter Analysis From TALWG.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) have a poorer prognosis than younger ones. Several factors contribute to the poor outcomes for this patient group. PATIENTS AND METHODS: This study investigated the epidemiology, clinical characteristics, treatment, and clinical outcomes of elderly Thai patients with AML. This 3-year, prospective, multicenter study was focused on Thai patients with AML aged over 60 years who were diagnosed between 2014 and 2016. RESULTS: Of 680 patients with AML, 235 elderly patients with AML (34.6%) were identified, with a mean age of 70 ± 8 years. Using a 3-group cytogenetic risk classification (favorable, intermediate, and adverse risk), the proportions of patients in each category were 3.6%, 73.8%, and 22.6%, respectively. The median follow-up time for surviving patients was 846 days. The median overall survival (OS) of the patients was 128.2 days (range, 0-1205 days), with a 1-year OS of 13%. From a multivariate analysis, the significant factors associated with an improved long-term OS were patients with an Eastern Cooperative Oncology Group performance status 0 to 2 and those receiving intensive therapy. CONCLUSION: Our study confirms the high prevalence of AML in elderly patients with generally poor outcomes. Selected patients with a good performance status and those who received intensive induction treatment could have a long-term survival.