What Is the Best Choice and Dose of Anthracycline for Induction Chemotherapy in Acute Myeloid Leukemia?

Treatment of patients with acute myeloid leukemia, medically fit to receive intensive chemotherapy, has been standardized over the past four decades and consists of an anthracycline administered along with continuous cytarabine. This combination is traditionally administered as seven days of cytarabine and three days of anthracycline, known as 7 + 3. Selecting the appropriate choice and dose of anthracycline for induction chemotherapy continues to be debated. Daunorubicin, used in three doses of either 45 mg/m2, 60 mg/m2 or 90 mg/m2, and idarubicin 12 mg/m2 are the two commonly used anthracyclines in clinical practice. Other anthracyclines including mitoxantrone and liposomal daunorubicin are incorporated in the treatment algorithm as well. Our understanding of the underlying biology of acute myeloid leukemia has significantly increased in the past decade, helping us formulate individualized treatment plans. In this chapter, we will discuss pivotal studies comparing the safety and efficacy of different types and doses of anthracyclines, focusing predominantly on daunorubicin and idarubicin. The details of the study design as well as subgroup analysis will be presented to determine which subset of patients with AML may benefit from a particular anthracycline

Early complications after biliary enteric anastomosis for benign diseases: A retrospective analysis

Background:Biliary-enteric anastomosis (BEA) is a common surgical procedure performed for the management of biliary obstruction or leakage that results from a variety of benign and malignant diseases. Complications following BEA are not rare. We aimed to determine the incidence and the factors associated with early complications occurring after BEA for benign diseases. Methods: We reviewed the medical records of all Patients who underwent BEA for benign diseases at our institution between January 1988 and December 2009. The primary outcome was early post operative complication. Logistic regression analysis was done to identify factors predicting the occurrence of complications. Results: Records of 79 Patients were reviewed. There were 34 (43%) males and 45 (57% females). Majority (53%) had choledocholithiasis with impacted stone or distal stricture, followed by traumatic injury to the biliary system (33%). Thirty-four Patients (43%) underwent a hepaticojejunostomy, 19 Patients (24%) underwent a choledochojejunostomy, and choledochoduodenostomy was performed in 26 Patients (33%). Early complications occurred in 39 (49%) Patients - 41% had local complications and 25% had systemic complications. Most frequent complications were wound infection (23%) and bile leak (10%). Four (5%) Patients died. On multivariate analysis, low serum albumin level (odds ratio = 16, 95% CI = 1.14-234.6) and higher ASA levels (odds ratio = 7, 95% CI: 1.22-33.34) were the independent factors predicting the early complications following BEA. Conclusions: Half of the Patients who underwent BEA for benign diseases had complications in our population. This high incidence may be explained by the high incidence of hypoalbuminemia and the high-risk group who underwent operation

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p\u3c0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p\u3c0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p\u3c0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes

Impact of sociodemographic factors on early mortality in acute promyelocytic leukemia in the United States: A time‐trend analysis

Background The survival of patients with acute promyelocytic leukemia (APL) has dramatically improved with the use of all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, because of the complexity of the initial management, early mortality (EM) remains a major contributor to treatment failure. It is less known whether advances in treatment, urgent access to specialized care, and broad availability of ATRA/ATO have reduced EM in the last 2 decades. Furthermore, the influence of sociodemographic factors on the risk of EM also remains unclear. Methods This study used the Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on the rates of EM and overall survival (OS) in patients with APL diagnosed between 1992 and 2015. Results In all, 2224 cases were identified (895 who were younger than 40 years and 1329 who were 40 years old or older); 47.9% had a county‐level median household income of $59,630 or higher, 49.0% belonged to counties where more than 31% of adults held at least a bachelor's degree, and 86.0% resided in urban areas. The rate of EM declined from 31.5% in 1992‐1995 to 15.9% in 2012‐2015 for all patients. It improved for patients younger than 40 years (27.4% in 1992‐1995 vs 5.4% in 2012‐2015; P < .001) and for patients 40 years old or older but not to the same extent (35.2% in 1992‐1995 vs 22.2% in 2012‐2015; P = .02). Importantly, improvements in EM were not seen among patients residing in rural areas, with the rate remaining higher than 20% in 2012‐2015. The 3‐year OS rate was 49.2% for patients with APL diagnosed in 1992‐1995 and 76.4% for patients diagnosed in 2012‐2015. Conclusions These findings confirm consistent improvements in EM and OS for patients with APL and point to the challenge of further extending these improvements in EM rates to older patients and to those living in rural areas. Early mortality and overall survival continue to improve for patients with acute promyelocytic leukemia over 2 decades. For patients 40 years old or older and those residing in rural areas, the risk of early mortality from acute promyelocytic leukemia remains unacceptably high

Impact of insurance status on the survival of younger patients diagnosed with acute promyelocytic leukemia in the United States

BACKGROUND Survival among patients diagnosed with acute promyelocytic leukemia (APL) has significantly improved with the use of all-trans retinoic acid and arsenic trioxide. However, the need for immediate diagnosis and access to specialized care and the cost associated with APL management can potentially act as barriers for disadvantaged patients. The influence of sociodemographic factors on the outcomes of patients with APL remains unclear. METHODS The authors used the National Cancer Institute's Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on survival in patients younger than 65 years with APL. RESULTS The authors identified 1787 cases: 816 who were younger than 40 years and 971 who were 40 years old or older. Insured patients who were younger than 40 years had an improved 5-year overall survival (OS) rate in comparison with patients without insurance. Among patients who were 40 years or older, having insurance (other than Medicaid) was associated with better survival than being a Medicaid beneficiary or being uninsured, whereas patients with Medicaid had improved 5-year OS in comparison with uninsured patients. In a multivariate analysis of patients younger than 40 years, a higher risk of death was associated with being male, being diagnosed in earlier years, and being uninsured. For patients who were 40 years old or older, mortality increased with increasing age and for both Medicaid and uninsured patients in comparison with insured patients. CONCLUSIONS Despite the high cure rate experienced by patients with APL, patients younger than 65 years without insurance and those 40 years old or older with Medicaid are at a significant disadvantage in comparison with patients with insurance. These findings point to an opportunity to improve survival in APL by addressing access to care

Safe and effective use of imatinib to treat Philadelphia chromosome positive acute lymphoblastic leukemia during pregnancy

Philadelphia chromosome positive (Ph+) B cell acute lymphoblastic leukemia (ALL) is extremely rare in pregnancy. Although the use of tyrosine kinase inhibitors (TKIs) has significantly improved outcomes of patients with Ph+ ALL, its use during pregnancy is not recommended due to the risk of fetal malformations. There are limited data on the use of TKIs during pregnancy and its long-term effects on the fetus. Within this context, we present a case of a 25-year-old woman diagnosed with Ph+ ALL during the third trimester and the safe and effective use of imatinib as treatment after failure of conventional chemotherapy