Epidemiology and early mortality patterns of acute promyelocytic leukemia in the United States.

There is a lack of contemporary population-based data on the epidemiology of acute promyelocytic leukemia (APL) in the United States. In this study, we aim to elucidate the demographics and early mortality patterns of APL hospitalizations utilizing the National Inpatient Sample database from 2016-2019. APL's annual age-adjusted incidence rate was 0.28/100,000, and the incidence increased with age, with the peak incidence in the 75-79 age group at 0.62/100,000. Whites constituted the majority of admissions at 67.7%, followed by Hispanics at 15.3%, the youngest racial group with a median age of 40 years. The median length of stay was 31 days for patients age < 60 years and 25 days for age ≥ 60 years (p < 0.001). After adjusting for confounders, the mean length of stay was 7 days higher in teaching hospitals compared to non-teaching hospitals (p 0.001). Overall mortality was 12.1% (22.2% for age ≥ 60 and 6.4% for < 60 years {p < 0.001}), and 56.5% of deaths happened before 7 days, with the median time to death being 6 days. The proportion of early deaths (< 7 days) in non-teaching hospitals was higher than late deaths (≥ 7 days) (19.2% vs. 5%; p 0.03), and admission to a teaching hospital was associated with lower mortality (adjusted odds ratio 0.27; p 0.01). Therefore, optimal treatment strategies need to be explored to mitigate this significant early mortality, especially in non-teaching hospitals.

Increased survival disparities among children and adolescents & young adults with acute myeloid leukemia: A Dutch population-based study.

For many cancers, adolescents and young adults (AYAs) have a poorer prognosis than pediatric patients. Our study evaluates survival outcomes of children (0-17 years) and AYAs (18-39 years) diagnosed with acute myeloid leukemia (AML) in the Netherlands between 1990 and 2015 (N = 2058) utilizing the population-based Netherlands Cancer Registry, which includes information on therapy and site of primary treatment. Five- and 10-year relative (disease-specific) survival were estimated for all patients, children and AYAs. Multivariable analyses were performed using generalized linear models (excess mortality) and logistic regression (early mortality). AYAs with AML had a substantially lower 5- and 10-year relative survival than children (5-year: 43% vs 58%; 10-year: 37% vs 51%). The gap in 5-year relative survival was largest (nearly 20 percent-points) in 2010 to 2015, despite survival improvements over time across all ages. The multivariable-adjusted excess risk of dying was 60% higher in AYAs (95% CI: 37%-86%). Early mortality (death within 30 days of diagnosis) declined over time, and did not differ between children and AYAs. In conclusion, AYAs diagnosed with AML in the Netherlands had a worse prognosis than pediatric patients. The survival gap seemed most pronounced in recent years, suggesting that improvements in care resulting in better outcome for children have not led to equal benefits for AYAs.

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group.

PURPOSE: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. MATERIALS AND METHODS: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. RESULTS: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). CONCLUSION: This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Differential Survival Outcomes Between De Novo and Secondary Acute Promyelocytic Leukemia: An Updated Population-based study.

BACKGROUND: Whether the characteristics and outcome of secondary acute promyelocytic leukemia (s-APL) are similar to de no APL (dn-APL) remains unknown. PATIENTS AND METHODS: Using the SEER database, we identified 3877 patients with APL diagnosed from 2000 to 2014, including 465 s-APL and 3412 dn-APL. RESULTS: Compared with dn-APL, s-APL werecharacterized by older median age, and a higher early mortality rate. Multivariate Cox model showed s-APL, older age, earlier year of diagnosis, and male gender were independently associated with worse survival. Notably, s-APL had a significantly inferior survival regardless of gender, race, marital status, and year of diagnosis. However, the difference between the 2 cohorts was only evident in younger patients (≤ 65 years) but was lost in older patients (> 65 years). Additionally, the majority of index cancer type was breast and prostate in female and male s-APL, respectively. Latency < 3 years was associated with superior survival in s-APL with breast index cancer. CONCLUSIONS: Inferior survival of s-APL points to the need for treatment improvement.

Gene mutations in acute promyelocytic leukemia early death in patients treated with arsenic trioxide alone

Purpose APL patients have recurrent alterations in FLT3, WT1, NRAS and KRAS. Gene mutations have a strong potential for involvement in pathogenesis and may have potential effects on the clinical manifestations. Gene mutations may even be associated with early death (ED) in APL patients. However, there is little published information on mutations in APL patients and whether they are attributed to early death. Methods In this study, we retrospectively analyzed the clinical data and gene mutations of 134 de novo APL patients. We detected the gene mutations by next-generation sequencing (NGS) to investigate the genetic predictors of early death in APL patients. According to the number of gene mutations per patient, the 134 APL patients were divided into three groups. All patients received arsenic trioxide (ATO) alone as induction therapy. The clinical data and gene mutations were compared and analyzed. Results A total of 134 APL patients were involved in the study. The clinical data of sex, WBC, PT, and DD, UA, and LDH level were significantly different between the three groups (P = 0.000, P = 0.000, P = 0.009, P = 0.020, P = 0.030, P = 0.001 and P = 0.014, respectively). Meanwhile, among them, the Sanz risk stratification and early death rate were significantly different (P = 0.001). The early death rate was 10.4%, and the median time to early death was 6.6 days (range 2–15 days). For the next-generation sequencing, a mean of 1.28 ± 1.06 mutations per patient was detected (range: 0–5). The univariate and the multivariate regression analysis showed that age > 50[HR = 1.666, CI (1.027–2.702), P = 0.039], high WBC count [HR = 4.702, CI (1.026–21.543), P = 0.046] and low ALB levels [HR = 4.547, CI (1.088–18.995), P = 0.038] were independent risk factors for early death in APL patients (AU)

Risk factors for early in-hospital death in patients who developed coagulopathy during induction therapy for acute promyelocytic leukemia: a nationwide analysis in Japan.

To prevent early death, management of coagulopathy is important in patients with untreated acute promyelocytic leukemia (APL). This study aimed to clarify factors associated with in-hospital death in patients with coagulopathy during induction therapy for APL. We retrospectively identified patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) and developed coagulopathy, using a nationwide inpatient database in Japan. Of 1115 eligible patients, 175 (15%) died at a median of 13 days (interquartile range, 7-30) after admission. In the multivariable analysis, compared with younger patients (aged < 40 years), the occurrence of in-hospital death was significantly more common among older patients (aged ≥ 40 and < 60 years: odds ratio = 2.58 [95% confidence interval: 1.29-5.19]; aged ≥ 60 and < 80 years: 7.66 [3.89-15.10]; aged ≥ 80 years: 16.83 [7.41-38.21]). Delayed initiation of ATRA and no conventional chemotherapy were significantly associated with in-hospital death (1.79 [1.16-2.76] and 2.40 [1.47-3.92], respectively). A total of 699 patients (63%) received anticoagulant therapies, but none of these was significantly associated with lower mortality. Although the present study was constrained by a lack of laboratory findings because of database limitations, the results showed that untreated patients with APL, especially the elderly, had a poor prognosis. Immediate administration of ATRA may reduce in-hospital mortality.

Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.

PURPOSE: Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS: We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS: We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION: Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.

Gene mutations in acute promyelocytic leukemia early death in patients treated with arsenic trioxide alone.

PURPOSE: APL patients have recurrent alterations in FLT3, WT1, NRAS and KRAS. Gene mutations have a strong potential for involvement in pathogenesis and may have potential effects on the clinical manifestations. Gene mutations may even be associated with early death (ED) in APL patients. However, there is little published information on mutations in APL patients and whether they are attributed to early death. METHODS: In this study, we retrospectively analyzed the clinical data and gene mutations of 134 de novo APL patients. We detected the gene mutations by next-generation sequencing (NGS) to investigate the genetic predictors of early death in APL patients. According to the number of gene mutations per patient, the 134 APL patients were divided into three groups. All patients received arsenic trioxide (ATO) alone as induction therapy. The clinical data and gene mutations were compared and analyzed. RESULTS: A total of 134 APL patients were involved in the study. The clinical data of sex, WBC, PT, and DD, UA, and LDH level were significantly different between the three groups (P = 0.000, P = 0.000, P = 0.009, P = 0.020, P = 0.030, P = 0.001 and P = 0.014, respectively). Meanwhile, among them, the Sanz risk stratification and early death rate were significantly different (P = 0.001). The early death rate was 10.4%, and the median time to early death was 6.6 days (range 2-15 days). For the next-generation sequencing, a mean of 1.28 ± 1.06 mutations per patient was detected (range: 0-5). The univariate and the multivariate regression analysis showed that age > 50[HR = 1.666, CI (1.027-2.702), P = 0.039], high WBC count [HR = 4.702, CI (1.026-21.543), P = 0.046] and low ALB levels [HR = 4.547, CI (1.088-18.995), P = 0.038] were independent risk factors for early death in APL patients. Furthermore, Kaplan-Meier survival analysis, univariate analysis, and the multivariate regression analysis showed that patients with multiple gene mutations [HR = 2.258, CI (1.115-4.571), P = 0.024], KRAS [HR = 5.136, CI (1.356-19.455), P = 0.016] and/or GATA2 [HR = 4.070, CI (1.287-12.877), P = 0.017] have a significantly higher early death rate. CONCLUSION: The results of this investigation show that both molecular markers and clinical variables should be used as potential predictors for early death in APL patients. Our results suggested that age > 50, high WBC count, low ALB levels, and the presence of multiple gene mutations, KRAS and/or GATA2 at the time of diagnosis were independent risk factors for early death in APL patients. For these patients, clinicians should be more cautious during the course of induction treatment.

Integration of Genomic and Transcriptomic Markers Improves the Prognosis Prediction of Acute Promyelocytic Leukemia.

PURPOSE: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA-arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. EXPERIMENTAL DESIGN: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). RESULTS: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P < 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. CONCLUSIONS: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.

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.

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach.

The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimated 10-year survival rates of ≥80%. Treatment of CBF-AML with fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin (GO) results in estimated 10-year survival rates of ≥75%. In younger/fit patients, the "3+7" regimen (3 days of daunorubicin + 7 days of cytarabine) produces less favorable results (estimated 5-year survival rates of 35%; worse in real-world experience); regimens that incorporate high-dose cytarabine, adenosine nucleoside analogs, and GO are producing better results. Adding venetoclax, FLT3, and IDH inhibitors into these regimens has resulted in encouraging preliminary data. In older/unfit patients, low-intensity therapy with hypomethylating agents (HMAs) and venetoclax is now the new standard of care. Better low-intensity regimens incorporating cladribine, low-dose cytarabine, and other targeted therapies (FLT3 and IDH inhibitors) are emerging. Maintenance therapy now has a definite role in the treatment of AML, and oral HMAs with potential treatment benefits are also available. In conclusion, AML therapy is evolving rapidly and treatment results are improving in all AML subsets as novel agents and strategies are incorporated into traditional AML chemotherapy. LAY SUMMARY: Ongoing research in acute myeloid leukemia (AML) is progressing rapidly. Since 2017, the US Food and Drug Administration has approved 10 drugs for different AML indications. This review updates the research and treatment pathways for AML.

Evaluación cardiovascular en pacientes con leucemia promielocítica tratados con el protocolo LPM-TOA / Cardiovascular evaluation of patients with promyelocytic leukemia treated with the PML-ATO protocol

Introducción: Con el protocolo LPM-TOA para tratamiento de la leucemia promielocítica, se han obtenido excelentes resultados, ya que se logra sobrevida global prolongada y posible curación de los enfermos. En la inducción se utilizan dos drogas cardiotóxicas: las antraciclinas y el trióxido de arsénico y en la consolidación los enfermos reciben una dosis elevada de arsénico. Objetivo: Evaluar la toxicidad cardíaca tardía en pacientes con leucemia promielocítica tratados según el protocolo LPM-TOA. Métodos: Se realizó un estudio observacional descriptivo, prospectivo y longitudinal que incluyó 20 pacientes tratados con protocolo LPM-TOA, seguidos en consulta entre enero y julio 2019. Los pacientes tenían más de dos años de haber recibido las drogas cardiotóxicas. Se revisaron las historias clínicas y se determinó la fracción de eyección ventricular izquierda y la deformidad longitudinal global, mediante ecocardiograma. Resultados: Se presentaron hombres y mujeres con igual frecuencia, edad promedio 41,5 ± 11,0 años. Durante la inducción, en menos de la mitad de los enfermos se suspendió el arsénico por elevación del segmento QT corregido; en la mayoría solo se suspendió por uno o dos días. La mayor parte de los pacientes tuvo la fracción de eyección ventricular izquierda con valores entre 61 y 70 por ciento y la deformidad longitudinal global fue - 24 - 22 por ciento Conclusiones: En los pacientes estudiados, el tiempo de haber recibido el trióxido de arsénico y la dosis recibida, no influyó en la función cardíaca(AU)

Introduction: The PML-ATO protocol for the treatment of promyelocytic leukemia has obtained excellent results, achieving high overall survival rates and the possible healing of patients. Two cardiotoxic drugs are used in the induction process: anthracyclines and arsenic trioxide, whereas during consolidation patients receive a high dose of arsenic. Objective: Evaluate the late cardiotoxicity in patients with promyelocytic leukemia treated by the PML-ATO protocol. Methods: An observational prospective longitudinal descriptive study was conducted of 20 patients treated with the PML-ATO protocol and followed-up in outpatient consultation from January to July 2019. More than two years had elapsed since the patients received the cardiotoxic drugs. A review was carried out of the patients' medical records and echocardiographic determination was made of left ventricular ejection fraction and overall longitudinal deformity. Results: Men and women presented the same frequency; mean age was 41.5 ± 11.0 years. During induction, arsenic was suspended in less than half the patients due to corrected QT elevation. In most it was only suspended for one or two days. Most patients had left ventricular ejection fraction values between 61 percent and 70 percent, whereas overall longitudinal deformity was - 24 percent - 22 percent. Conclusions: In the patients studied, cardiac function was not affected by the time elapsed since arsenic trioxide administration or the dose received(AU)

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

Safety and efficacy of different doses of anthracyclines combined with arsenic trioxide and all-trans retinoic acid in the treatment of de novo acute promyelocytic leukemia.

OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of different doses of anthracyclines combined with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) for induction in newly diagnosed acute promyelocytic leukemia (APL). METHODS: One hundred and forty patients were included between January 2011 and December 2017. Seventy patients received low dose anthracycline, ATO and ATRA for induction chemotherapy; and other seventy patients received standard dose anthracycline, ATO and ATRA for induction chemotherapy. RESULTS: The outcomes of both groups were similar: low dose group versus standard dose group: early mortality 5.7% vs. 10.0% (P = 0.532), disease-free survival (DFS), probabilities of overall-survival (OS) at 2 years 94.6% vs. 95.1% (P = 0.657), 92.8% vs. 88.2% (P = 0.951), respectively. However, the standard-dose group was associated with a longer duration of neutropenia (p < 0.001) and thrombocytopenia (p < 0.001), more volumes of platelets (p = 0.037) and red blood cell transfusions (p < 0.001), and a higher rate of infections (p = 0.042). CONCLUSION: Low-dose group achieves outcomes similar to those of standard dose group for APL patients, but the low-dose group may be even safer than standard-dose group. So the low-dose anthracycline may be a better choice for newly diagnosed APL patients.

Outcomes for Patients With Acute Promyelocytic Leukemia in South Africa.

BACKGROUND: The characteristics and outcomes of patients with acute promyelocytic leukemia (APL) from sub-Saharan Africa have not been published. PATIENTS AND METHODS: We report retrospectively on consecutively diagnosed APL patients treated in Cape Town, South Africa, during 1998-2019. A total of 69 patients were treated, of whom 27 (39%) were classified as having high risk APL. RESULTS: Early death rates at 7 and 30 days were 7% and 13%, respectively, including 4 patients who died before any treatment could be administered. Overall survival at 3 years was 76.5% (95% confidence interval, 63.9-85.2) for the entire cohort, and 82.5% (95% confidence interval, 69.7-90.2) if patients who died within 7 days of diagnosis were excluded. For 13 patients (18.8%), there was a delay of 5 or more days from time of initial presentation at a peripheral hospital until arrival at the leukemia center and administration of all-trans retinoic acid; only 1 of these patients died within 30 days. CONCLUSION: Despite the challenges faced in the public healthcare system of a developing country, outcomes of APL patients treated at our center are similar to outcomes from developed countries.

Early death in acute promyelocytic leukemia: Evidence from a rural cancer center.

BACKGROUND: Early death is still the characteristic feature of acute promyelocytic leukemia (APL) despite the advances in the treatment regimen. Analyzing the incidence of early death would prove beneficial as no much substantial information is available pertaining to the rural population. The present study analyzed the incidence of APL-associated early death, its clinical characteristics, and outcome among acute myeloid leukemia patients. METHODS: This retrospective study included patients catering to the rural areas of Vijayawada (Andhra Pradesh, India) from January 2013 to June 2017. Chi-square test, Fisher's exact test, independent sample median test, and Kaplan-Meier test for probability of survival were used. RESULTS: Of the 204 acute myeloid cases, 24% cases (median age = 30 years; range=8 to 68 years) were identified as APL. Early death rate was 34.6%, who expired within 30 days from diagnosis with 65% suffering high disease risk. The median time from admission to death was 2 days (range 0-18). Cause of early death was majorly due to hemorrhage (64%). Moreover, 47.1% of early death patients received no prior antileukemic treatment. The overall 5-year cumulative disease-free survival rate among patients with APL was 76% where high disease risk patients had the least disease-free survival (65%-75%), whereas intermediate and low-risk patients had >80% and 100% disease-free survival rate, respectively. CONCLUSION: Early diagnosis and timely intervention might help to prevent early death as our findings clearly indicate poor awareness of disease and lack of early intervention among the rural population.

Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia.

Significant advancements have been achieved with regard to the outcomes of acute promyelocytic leukemia (APL) patients through the introduction of all-trans retinoic acid; however, early hemorrhagic death and differentiation syndrome remain the major causes of remission induction failure in patients with APL. To investigate early death, serious hemorrhage, and differentiation syndrome during remission induction therapy in terms of incidence, risk factors, influence on outcomes, and prophylactic effects of several new anticoagulants, the results of 344 patients enrolled in the Acute Promyelocytic Leukemia 204 study conducted by the Japan Adult Leukemia Study Group were analyzed. Early death was observed in 16 patients (4.7%), of whom 14 had serious hemorrhage and 2 had differentiation syndrome. Serious hemorrhage and differentiation syndrome of grade 2 or higher were observed in 21 and 54 patients, respectively. Patients who achieved complete remission had a 7-year disease-free survival of 84.8% if they did not experience serious hemorrhage and 40.0% if they experienced serious hemorrhage during remission induction therapy (P = 0.001). Risk factor analyses showed that higher white blood cell count was associated with early death, higher white blood cell count and lower platelet count with serious hemorrhage, and leukocytosis during induction therapy and higher body surface area with differentiation syndrome. In conclusion, these results indicate that patients with such high-risk features may benefit from more intensive supportive care. The hemorrhagic risk was not relieved by the introduction of new anticoagulants. Further studies are required to establish the predictive impact of body surface area on differentiation syndrome. This trial is registered with UMIN-CTR as C000000154 on September 13, 2005.