Is obesity a prognostic factor for acute myeloid leukemia outcome?

Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity, measured by body mass index (BMI), affected outcome in 329 adult AML patients treated with high-dose cytarabine and idarubicin-containing regimens administered according to actual body weight. Age ≥ 60, unfavorable karyotype, secondary AML, and positive smoking status had adverse impact on overall survival in a multivariate analysis, while BMI did not. We conclude that high BMI should not be a barrier to administer high-dose cytarabine-containing regimens for AML induction.     

Dose intensity of preparative regimens for acute myeloid leukemia – One-size-fits-all or tailor-made?

Both toxicity and leukemia eradication correlate with the intensity of the transplant preparative regimen. How much any specific patient benefits from increased dose intensity depends, in part, on his/her ability to tolerate higher-dose therapy and the status of the leukemia being treated. Newer tools that include not only age and performance status, but also comorbidity indices, are useful for predicting the ability of a patient to tolerate therapy and should allow for the development of models predicting risk/benefit ratios for the use of more or less intense preparative regimens for any specific patient. If attempts are made to build such models, recent transplant data should be used, since advances in ancillary transplant measures (including better approaches to infection management and treatment of graft-vs-host disease) have led to improved transplant outcomes over the last decade. Ultimately, the goal should be to create preparative regimens with greater antileukemic intensity but with minimal extramedullary toxicity.     

Which novel agents for acute myeloid leukemia are likely to change practice?

There has been little progress in drug development in acute myeloid leukemia (AML) in the recent past. This recently changed with the approval of several therapies for patients with this disease and prompts one to consider which therapies may change practice for patients with AML. To change practice, a therapy must be adopted as a standard of care intervention based on its efficacy and safety profile and must endure as the accepted treatment for a particular indication for a significant period of time. Here I attempt to determine which therapies, approved or in development, may change practice in the field of AML.     

Is secondary leukemia an independent poor prognostic factor in acute myeloid leukemia?

Secondary leukemia is a poorly defined term that often refers to the development of acute myeloid leukemia (AML) following the history of a previous disease, such as a myelodysplastic syndrome or a chronic myeloproliferative disorder. Secondary leukemia can also be a consequence of treatment with chemotherapy, including alkylating agents and topoisomerase II inhibitors, and/or radiotherapy, or due to exposure to environmental carcinogens. Outcomes for this large and variable group of patients with secondary AML have been poor compared to people who develop AML de novo. The question arises whether a diagnosis of secondary leukemia per se indicates a poor prognosis or whether their bad outcomes result from an association with certain morphologic and biologic characteristics. Morphologic dysplasia in de novo AML is related to unfavorable cytogenetics, but has no independent prognostic relevance under the conditions of intensive chemotherapy. While there is no significant correlation between cytogenetic risk groups and dysplasia, cytogenetic features do have an impact on outcome among both de novo and secondary AML patients. In various subgroups of secondary AML, the spectrum of cytogenetic abnormalities is similar to de novo AML, but the frequency of abnormalities associated with unfavorable and intermediate risk cytogenetics, such as a complex karyotype, trisomy 8, monosomy 7, and others, is higher in secondary AML. The survival of patients with therapy-related myeloid leukemia (t-AML) is generally shorter than for those with de novo AML within the same cytogenetic risk group. Across the population of t-AML, however, survival varies according to cytogenetic risk group, with longer survival in patients with favorable-risk karyotypes. The term secondary AML is too broad and imprecise to be of importance and should not be used. These AML patients should be enrolled on front-line chemotherapy trials and should be stratified by pretreatment disease status and exposure history, if necessary. Most importantly, the molecular and genetic differences that appear to determine the phenotype and the outcome of these patients need to be investigated further.     

Blood transfusion requirements for patients undergoing chemotherapy for acute myeloid leukemia how much is enough?

Although essential in the management of AML, there is little information quantitating transfusion requirements for these patients. We evaluated 111 consecutive adults treated for AML, showing that approximately 150 blood donors are required to adequately cater for a single patient's complete therapy with little variation for age, prognostic group or intensity of treatment.     

Why isn't there a one-size-fits-all approach for relapsed/refractory acute myeloid leukemia? Insights into different variables for decision-making

Relapsed refractory acute myeloid leukemia (R/R AML) has a poor prognosis. While the heterogeneity and diversity of R/R AML pose hurdles towards defining a standard of care, there have been various advances over the years. These, however, have added to the complexity of decision-making for R/R AML. This review has summarized evidence that will provide insights into factors that influence treatment choices in R/R AML and determine whether ongoing clinical trials can aid in identifying a standard approach for different sub-groups of patients.     

Predictive value of ¹⁸F-fluorodeoxyglucose PET/CT for transarterial chemolipiodolization of hepatocellular carcinoma

AIM: To investigate the correlation of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) with clinical features and the prediction of treatment response.METHODS: A total of 83 hepatocellular carcinoma (HCC) patients undergoing ¹⁸F-FDG PET before transarterial chemolipiodolization with systemic chemo-infusion between October, 2006 and May, 2009 were retrospectively enrolled. The patients included 68 men and 15 women (mean age, 60 ± 10.7 years). The effect of ¹⁸F-FDG-monitored PET uptake on clinical features and on the evaluated treatment response was ascertained with modified Response Evaluation Criteria in Solid Tumors. The PET parameters of maximal standardized uptake value of the tumor (Tsuv_max), the ratio of the tumor maximal standardized uptake value (SUV) to the liver maximal SUV (Tsuv_max/Lsuv_max) and the ratio of tumor maximal SUV to the liver mean SUV (Tsuv_max/Lsuv_mean) were tested as predictive factors.RESULTS: Among the 3 SUV parameters, the Tsuv_max/Lsuv_mean ratio (cutoff value of 1.90) was significantly associated with tumor burden including tumor size, tumor number, α-fetoprotein levels and tumor stage (P < 0.001, P = 0.008, P = 0.011, P < 0.001, respectively). The objective response rates in patients with a high SUV ratio (≥ 1.90) were significantly better than those with a low SUV ratio (< 1.90) (P = 0.020). The overall survival rates of patients exhibiting a low Tsuv_max/Lsuv_mean ratio (< 1.90) and those with a high SUV ratio (≥ 1.90) was 38.2 and 10.3 mo, respectively (P < 0.01). However, the time to progression showed no significant difference between the groups (P = 0.15).CONCLUSION: ¹⁸F-FDG PET can be an important predictor of HCC treatment. In particular, the Tsuv_max/Lsuv_mean ratio (cutoff value of 1.90) can provide useful information in treatment prognosis for HCC patients treated with locoregional therapy.     

Dose intensity for induction in acute myeloid leukemia: what,when, and for whom?

Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a deeper understanding of the genetic makeup of AML, has led to remission- inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered singleagent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.     

Post-remission therapy in acute myeloid leukemia: Are we ready for an individualized approach?

Recent advances in remission induction treatment strategies for acute myeloid leukemia (AML) have improved the rates of complete remission (CR) and overall survival (OS), owing to a concerted effort to tailor therapies toward specific AML subtypes. However, without effective post-remission therapy, most patients will relapse. The extent to which post-remission therapies is individualized in the current paradigm is quite varied. Core binding factor (CBF) AML is typically treated with post-remission high-dose cytarabine (HiDAC) without allogeneic hematopoietic stem cell transplantation (HSCT), whereas those with intermediate or adverse-risk cytogenetics are treated with post-remission cytarabine followed by allogeneic HSCT in CR1 when feasible. A lack of clarity regarding the proper dosing of post-remission cytarabine has made consensus building on dosing and schedule a challenge. CBF AML benefits most from high-dose cytarabine (HiDAC), and dasatinib appears promising as an adjunct for those for KIT-mutated CBF AML. Other than series using CPX-351 or lomustine in older adults, multiagent chemotherapy approaches have resulted in excess toxicity without a survival benefit. Neither hypomethylating agents nor gemtuzumab ozogamicin have shown a material OS benefit. Targeted agents such as FLT3 inhibitors and IDH1/IDH2 inhibitors show potential for the patients who harbor these druggable targets, but few data are available. Many studies evaluating post-remission strategies to target AML in the MRD-positive state are already underway, and these remain a promising area of investigation.     

Amonafide: a future in treatment of resistant and secondary acute myeloid leukemia?

Development of the novel topoisomerase II inhibitor, amonafide, began almost 40 years ago. The drug was selected for further investigation owing to evidence of marked antineoplastic efficacy in preclinical models of cancer. When its usefulness in the treatment of various solid malignancies proved limited, focus was shifted to establishing its use as an antileukemic agent, specifically against secondary and treatment-associated acute myeloid leukemia (AML). While Phase I and II studies gave rise to hopes that amonafide might hold the key to treating older patients, including those with multidrug resistant, cytogenetically unfavorable secondary and treatment-associated AML, when used in combination with cytarabine, it failed to demonstrate a survival advantage over standard-of-care therapy in randomized studies. This article will outline the development of amonafide from the laboratory to the bedside and discuss the potential place that this agent has in the current management of AML.