Treatment regimens in patients over 64 years with acute myeloid leukaemia: a retrospective single-institution, multi-site analysis.

OBJECTIVES: The aim of this study is to investigate the effect of treatment choice on survival, transfusion needs and hospitalizations in patients > 64 years old with newly diagnosed acute myeloid leukaemia (AML). MATERIAL AND METHODS: This study retrospectively analysed patients over 64 years with AML diagnosed at a regional healthcare network in Switzerland between 2017 and 2020. Patients underwent four therapy groups: intensive chemotherapy (IC), hypomethylating agent in combination with the BCL2-Inhibitor venetoclax (HMA + VEN), hypomethylating agents alone (HMA) or best supportive care (BSC). RESULTS: Of 54 patients 12 (22%) were selected for IC, 13 (24%) for HMA + VEN, 17 (32%) for HMA and 12 (22%) for BSC. The median overall survival of the patients was 76 days, with a significant difference in the four therapy groups (IC 119 days, HMA + VEN 732 days, HMA monotherapy 73 days and BSC 12 days Log-Rank Test Chi2(2): p < 0.001). Patients with HMA + VEN spent significantly less time in the hospital 6.8 days/month compared to IC (19.5 days/month), HMA (20.5 days/month) and BSC (10.5 days/month) (p = 0.005). Transfusion needs were the highest in IC (7.0 RBC/month, 8.0 PC/month) (p = 0.023), whereas there was no difference between HMA + VEN (2.5 RBC/month, 3.2 PC/month), HMA monotherapy (5.3 RBC/month, 6.2 PC/month) and BSC (3.0 RBC/month, 1.4 PC/month). CONCLUSION: Our real-world data demonstrate superior OS rates of HMA + VEN when compared to IC, HMC or BSC, with a favourable side effect profile with regard to transfusion needs or hospitalization days.Abbreviations: AML, acute myeloid leukaemia; BCL2, B-cell leukaemia/lymphoma-2; BSC, best supportive care; CR, complete response; Cri, complete response with incomplete haematologic regeneration; FLT3, Fms Related Receptor Tyrosine Kinase 3; EKOS, Ethikkomission Ostschweiz; ELN, European Leukaemia Net; HMA, hypomethylating agent; IC, intensive chemotherapy; IDH, Isocitratdehydrogenase; LDAC, low-dose Cytarabine; NCCN, National Comprehensive Cancer Network; OS, overall survival; PC, platelet concentrate; RBC, red blood cell; RCT, randomized controlled trials; t-AML, therapy relative acute myeloid leukaemia'; VEN, venetoclax.

Clinical status of induction therapy incorporating a hypomethylating agent for newly diagnosed adult acute myeloid leukemia compared to the standard 7+3 regimen.

INTRODUCTION: Cytarabine and anthracycline combination therapy (7 + 3 regimen) is the standard care for induction chemotherapy in adult patients with acute myeloid leukemia (AML). Although this intensive regimen achieves a high response rate, it is highly toxic, especially in elderly or frail patients. Hypomethylating agents approved initially for high-risk myelodysplastic syndrome had longer survival times than conventional care in elderly patients with newly diagnosed AML. AREAS COVERED: We summarize the latest information regarding induction therapy using hypomethylating agents (azacitidine and decitabine) for newly diagnosed AML. EXPERT OPINION: For untreated patients ineligible for an intensive regimen, a phase III trial exhibited the survival benefit of adding the highly selective BCL2 inhibitor venetoclax to azacitidine. The National Comprehensive Cancer Network guidelines recommend azacitidine or decitabine plus venetoclax as an option for patients with poor-risk AML, including those with TP53 mutations and AML with the cytogenetic features of myelodysplastic syndrome. Future studies should evaluate positioning this combination as an induction therapy for younger patients eligible for hematopoietic stem cell transplantation. Without randomized trials, propensity score matching analysis suggested a comparable prognosis between azacitidine combination and intensive chemotherapy. Considering the feasibility of a doublet regimen incorporating azacitidine, a triplet regimen should be examined.

Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: Acute myeloid leukaemia with mutated NPM1 is associated with high CD33 expression and intermediate-risk cytogenetics. The aim of this study was to evaluate intensive chemotherapy with or without the anti-CD33 antibody-drug conjugate gemtuzumab ozogamicin in participants with newly diagnosed, NPM1-mutated acute myeloid leukaemia. METHODS: This open-label, phase 3 trial was conducted at 56 hospitals in Germany and Austria. Eligible participants were 18 years or older and had newly diagnosed NPM1-mutated acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Participants were randomly assigned, using age as a stratification factor (18-60 years vs >60 years), 1:1 to the two treatment groups using allocation concealment; there was no masking of participants and investigators to treatment groups. Participants received two cycles of induction therapy (idarubicin, cytarabine, and etoposide) plus all-trans retinoic acid (ATRA) followed by three consolidation cycles of high-dose cytarabine (or an intermediate dose for those older than 60 years) and ATRA, without or with gemtuzumab ozogamicin (3 mg/m2 administered intravenously on day 1 of induction cycles 1 and 2, and consolidation cycle 1). The primary endpoints were short-term event-free survival and overall survival in the intention-to-treat population (overall survival was added as a co-primary endpoint after amendment four of the protocol on Oct 13, 2013). The secondary endpoints were event-free survival with long-term follow-up, rates of complete remission, complete remission with partial haematological recovery (CRh), and complete remission with incomplete haematological recovery (CRi), cumulative incidences of relapse and death, and number of days in hospital. This trial is registered with ClinicalTrials.gov (NCT00893399) and has been completed. FINDINGS: Between May 12, 2010, and Sept 1, 2017, 600 participants were enrolled, of which 588 (315 women and 273 men) were randomly assigned (296 to the standard group and 292 to the gemtuzumab ozogamicin group). No difference was found in short-term event-free survival (short-term event-free survival at 6-month follow-up, 53% [95% CI 47-59] in the standard group and 58% [53-64] in the gemtuzumab ozogamicin group; hazard ratio [HR] 0·83; 95% CI 0·65-1·04; p=0·10) and overall survival between treatment groups (2-year overall survival, 69% [63-74] in the standard group and 73% [68-78] in the gemtuzumab ozogamicin group; 0·90; 0·70-1·16; p=0·43). There was no difference in complete remission or CRi rates (n=267 [90%] in the standard group vs n=251 [86%] in the gemtuzumab ozogamicin group; odds ratio [OR] 0·67; 95% CI 0·40-1·11; p=0·15) and complete remission or CRh rates (n=214 [72%] vs n=195 [67%]; OR 0·77; 0·54-1·10; p=0·18), whereas the complete remission rate was lower with gemtuzumab ozogamicin (n=172 [58%] vs n=136 [47%]; OR 0·63; 0·45-0·80; p=0·0068). Cumulative incidence of relapse was significantly reduced by gemtuzumab ozogamicin (2-year cumulative incidence of relapse, 37% [95% CI 31-43] in the standard group and 25% [20-30] in the gemtuzumab ozogamicin group; cause-specific HR 0·65; 0·49-0·86; p=0·0028), and there was no difference in the cumulative incidence of death (2-year cumulative incidence of death 6% [4-10] in the standard group and 7% [5-11] in the gemtuzumab ozogamicin group; HR 1·03; 0·59-1·81; p=0·91). There were no differences in the number of days in hospital across all cycles between treatment groups. The most common treatment-related grade 3-4 adverse events were febrile neutropenia (n=135 [47%] in the gemtuzumab ozogamicin group vs n=122 [41%] in the standard group), thrombocytopenia (n=261 [90%] vs n=265 [90%]), pneumonia (n=71 [25%] vs n=64 [22%]), sepsis (n=85 [29%] vs n=73 [25%]). Treatment-related deaths were documented in 25 participants (4%; n=8 [3%] in the standard group and n=17 [6%] in the gemtuzumab ozogamicin group), mostly due to sepsis and infections. INTERPRETATION: The primary endpoints of the trial of event-free survival and overall survival were not met. However, an anti-leukaemic efficacy of gemtuzumab ozogamicin in participants with NPM1-mutated acute myeloid leukaemia is shown by a significantly lower cumulative incidence of relapse rate, suggesting that the addition of gemtuzumab ozogamicin might reduce the need for salvage therapy in these participants. The results from this study provide further evidence that gemtuzumab ozogamicin should be added in the standard of care treatment in adults with NPM1-mutated acute myeloid leukaemia. FUNDING: Pfizer and Amgen.

A multiparametric niche-like drug screening platform in acute myeloid leukemia.

Functional precision medicine in AML often relies on short-term in vitro drug sensitivity screening (DSS) of primary patient cells in standard culture conditions. We designed a niche-like DSS assay combining physiologic hypoxia (O2 3%) and mesenchymal stromal cell (MSC) co-culture with multiparameter flow cytometry to enumerate lymphocytes and differentiating (CD11/CD14/CD15+) or leukemic stem cell (LSC)-enriched (GPR56+) cells within the leukemic bulk. After functional validation of GPR56 expression as a surrogate for LSC enrichment, the assay identified three patterns of response, including cytotoxicity on blasts sparing LSCs, induction of differentiation, and selective impairment of LSCs. We refined our niche-like culture by including plasma-like amino-acid and cytokine concentrations identified by targeted metabolomics and proteomics of primary AML bone marrow plasma samples. Systematic interrogation revealed distinct contributions of each niche-like component to leukemic outgrowth and drug response. Short-term niche-like culture preserved clonal architecture and transcriptional states of primary leukemic cells. In a cohort of 45 AML samples enriched for NPM1c AML, the niche-like multiparametric assay could predict morphologically (p = 0.02) and molecular (NPM1c MRD, p = 0.04) response to anthracycline-cytarabine induction chemotherapy. In this cohort, a 23-drug screen nominated ruxolitinib as a sensitizer to anthracycline-cytarabine. This finding was validated in an NPM1c PDX model.

Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators.

Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell-like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification. SIGNIFICANCE: Immunophenotype and somatic mutations play a significant role in treatment approach and risk stratification of acute leukemia. We conducted an integrated genomic analysis of pediatric myeloid malignancies and found that a combination of genetic and transcriptional readouts was superior to immunophenotype and genomic mutations in identifying biological subtypes and predicting outcomes. This article is highlighted in the In This Issue feature, p. 549.

[Stratified treatment of fit and unfit acute myeloid leukemia].

The etiology and pathogenesis of acute myeloid leukemia (AML) have been elucidated at chromosomal and genetic levels. The classification and prognosis for its treatment has clearly involved specific chromosomal aberrations and genetic mutations. The recent comprehensive genomic analysis represented by next-generation sequencers has led to discovering new genetic mutations in AML. These findings have not only been applied clinically as prognostic factors and MRD markers but also contributed to the development of new molecular-targeting drugs. Many new drugs have already been approved in the USA and Europe, and new stratified treatments have tried to incorporate them. With the advent of venetoclax, treatment strategies, especially for patients with poor prognosis and who are unfit, have been substantially revised, and the maintenance therapy for AML is also being reevaluated in accordance to the National Comprehensive Cancer Network guidelines. This article will review the current status of AML treatment in Japan and according to Western guidelines.

Isochromosome 11q is Associated with Unique Characteristics and Poor Prognosis in Patients with Acute Myeloid Leukemia.

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.

The Application of Next-generation Sequencing Tumor Molecular Profiling in the Diagnosis and Management of a Case of Acute Myelogenous Leukemia With MLL-PTD in a Pediatric Heart Transplant Recipient.

A 6-year-old girl with a history of heart transplantation was diagnosed with myelodysplastic syndrome, which progressed to acute myelogenous leukemia. Comprehensive genomic profiling of her tumor discovered an MLL-PTD (partial tandem duplication) and she received chemotherapy and a hematopoietic stem cell transplant (HSCT). She subsequently relapsed and tumor molecular profiling was repeated, revealing 2 new potentially targetable mutations (FLT3 and IDH2). A novel treatment regimen targeting these mutations with sorafenib and azacitidine without using cytotoxic chemotherapy produced remission and she subsequently pursued a second HSCT. She remains disease-free 17 months after HSCT. This case report demonstrates how repeated tumor molecular profiling provided novel actionable information for the diagnosis and management at 2 timepoints.

Safety and efficacy of BAY1436032 in IDH1-mutant AML: phase I study results.

The mutant IDH1 (mIDH1) inhibitor BAY1436032 demonstrated robust activity in preclinical AML models, supporting clinical evaluation. In the current dose-escalation study, BAY1436032 was orally administered to 27 mIDH1 AML subjects across 4 doses ranging from 300 to 1500 mg twice-daily. BAY1436032 exhibited a relatively short half-life and apparent non-linear pharmacokinetics after continuous dosing. Most subjects experienced only partial target inhibition as indicated by plasma R-2HG levels. BAY1436032 was safe and a maximum tolerated dose was not identified. The median treatment duration for all subjects was 3.0 months (0.49-8.5). The overall response rate was 15% (4/27; 1 CRp, 1 PR, 2 MLFS), with responding subjects experiencing a median treatment duration of 6.0 months (3.9-8.5) and robust R-2HG decreases. Thirty percent (8/27) achieved SD, with a median treatment duration of 5.5 months (3.1-7.0). Degree of R-2HG inhibition and clinical benefit did not correlate with dose. Although BAY1436032 was safe and modestly effective as monotherapy, the low overall response rate and incomplete target inhibition achieved at even the highest dose tested do not support further clinical development of this investigational agent in AML.

Ex vivo drug screening defines novel drug sensitivity patterns for informing personalized therapy in myeloid neoplasms.

Precision medicine approaches such as ex vivo drug sensitivity screening (DSS) are appealing to inform rational drug selection in myelodysplastic syndromes (MDSs) and acute myeloid leukemia, given their marked biologic heterogeneity. We evaluated a novel, fully automated ex vivo DSS platform that uses high-throughput flow cytometry in 54 patients with newly diagnosed or treatment-refractory myeloid neoplasms to evaluate sensitivity (blast cytotoxicity and differentiation) to 74 US Food and Drug Administration-approved or investigational drugs and 36 drug combinations. After piloting the platform in 33 patients, we conducted a prospective feasibility study enrolling 21 patients refractory to hypomethylating agents (HMAs) to determine whether this assay could be performed within a clinically actionable time frame and could accurately predict clinical responses in vivo. When assayed for cytotoxicity, ex vivo drug sensitivity patterns were heterogeneous, but they defined distinct patient clusters with differential sensitivity to HMAs, anthracyclines, histone deacetylase inhibitors, and kinase inhibitors (P < .001 among clusters) and demonstrated synergy between HMAs and venetoclax (P < .01 for combinations vs single agents). In our feasibility study, ex vivo DSS results were available at a median of 15 days after bone marrow biopsy, and they informed personalized therapy, which frequently included venetoclax combinations, kinase inhibitors, differentiative agents, and androgens. In 21 patients with available ex vivo and in vivo clinical response data, the DSS platform had a positive predictive value of 0.92, negative predictive value of 0.82, and overall accuracy of 0.85. These data demonstrate the utility of this approach for identifying potentially useful and often novel therapeutic drugs for patients with myeloid neoplasms refractory to standard therapies.

Fatal Intracerebral Hemorrhage During "Muay Thai" in a 21-Year-Old Man With Undiagnosed Acute Myeloid Leukemia: Spontaneous or Posttraumatic Hemorrhage?

Acute myeloid leukemia (AML) is characterized by the rapid growth of abnormal white blood cells in the bone marrow that interferes with the production of normal blood cells. This disease is burdened by a high risk of bleeding complications involving central nervous system hemorrhages, purpura, gingival bleeding, and gastrointestinal bleeding. In this article, the authors report a case of a fatal intracerebral hemorrhage in a 21-year-old man who was affected by an undiagnosed AML. The subject practiced a combat sport (Muay Thai), and 2 days before his last training, he was involved in a fight where the aggressor punched him in the face; however, after the fight, he did not claim of any symptoms. The current case highlights the importance of the role of the forensic pathologist because only through a careful and complete circumstantial, autoptic, and histological analysis it is possible to date the origin of a cerebral hemorrhage and establish whether it is spontaneous or posttraumatic in subjects with undiagnosed preexisting diseases. Through an integrated study, it is also important to date the lesion and identify the traumatic event responsible of the bleeding. Finally, this case has a relevant clinical importance relatively to sports medicine, where it would be appropriate that athletes undergo blood test as a preventive measure. In fact, in presence of an acute hematological disease, such as AML, even mild traumatic injuries may be fatal.

Network-based analysis with primary cells reveals drug response landscape of acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the most common, complex, and heterogeneous hematological malignancies in adults. Despite progresses in understanding the pathology of AML, the 5-year survival rates still remain low compared with CML, CLL, etc. The relationship between genomic features and drug responses is critical for precision medication. Herein, we depicted a picture for response of 145 drugs against 33 primary cell samples derived from AML patients with full spectrum of genomic features assessed by whole exon sequencing and RNA sequencing. In general, most of the samples were much more sensitive to the combinatorial chemotherapy regimens than the single chemotherapy drugs. Overall, these samples were moderately sensitive to the Traditional Chinese Medicine (TCM) and the targeted drugs. In the weighted gene coexpression network analysis (WGCNA), the TCM and targeted therapies displayed similar genetic signatures in the gene module correlation. Meanwhile, the expression of miRNAs, lncRNAs, and mRNAs did not display apparent gene module correlations among those different types of therapies. In addition, the combinatorial chemotherapy bear more module correlations than the single drugs. Interestingly, we found that the gene mutations and drug response were not enriched in any WGCNA module analysis. Most of the sensitive drug response biomarkers were enriched in the ribosome, endocytosis, cell cycle, and p53 associated signaling pathways. This study showed that gene expression modules might show better correlation than gene mutations for drug efficacy predictions.

How I investigate acute myeloid leukemia.

Acute myeloid leukemia (AML) is a neoplasm of immature myeloid cells and is associated with a wide variety of clinical presentations, morphological features, immunophenotypes, and genetic findings. Recent advances in identification of cytogenetic abnormalities and mutations have provided novel insights into the pathogenesis of AML. Based on the above-mentioned parameters, the World Health Organization (WHO) classified AML into 25 subtypes, including 2 provisional entities, which differ in prognosis and treatment. In addition, certain mutations are associated with germline predisposition and increase the risk of inherited AML, which warrants family screening. Therefore, precise diagnosis and classification of AML are the most important steps in patient management. Both these steps require incorporation of history, clinical presentation, and laboratory results with studies performed by a pathologist. Pathologist-initiated studies include morphologic evaluation on the bone marrow aspirate and/or core biopsy, immunophenotyping by flow cytometry and/or immunohistochemistry, cytogenetic analysis by karyotyping and/or fluorescence in situ hybridization, and molecular testing using gene panels and/or next-generation sequencing. A similar approach is employed during follow-up of patients after beginning treatment. Here, we describe in detail the various aspects of the workup, including purpose, limitations, and practice guidelines for the different studies. The process of choosing appropriate materials for the different studies is also addressed. We also provide an algorithm for the workup and risk stratification of AML based on guidelines recommended by the WHO, College of American Pathologists, National Comprehensive Cancer Network, American Society of Clinical Oncology, European Society of Medical Oncology, and the European LeukemiaNet.

Fluorescence spectral detection of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML): A novel photodiagnosis strategy.

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cell, showing a rapid growth of lymphoblastic immature cells. Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells. Early diagnosis is crucial for the effective treatment of these patients. The current standard procedure of diagnosis is extensive blood count analysis, microscopic morphological investigations, bone marrow biopsy and flow-cytometer which are all time- consuming and expensive. Here we demonstrate the advantage a new technique for the diagnosis of ALL and AML based on the fluorescence spectra of blood plasma and RBCs samples from the above patients. Based on the 85 patients analyzed the results reveal that our approach could discriminate the two malignancies unambiguously from the normal with 88 % sensitivity and 80 % specificity. The abnormal decrease in the level of amino acid, tryptophan and coenzyme NADH and abnormal increase in the other amino acid, tyrosine and another coenzyme FAD, (both in comparison to the normal control) act as malignancy indicative biomarkers. Since the contrast parameter between the normal and malignant samples is four- fold, the potential for early detection of leukemia is high. The instrumentation and technique are new and simple; hence may have significant supplementary or complementary value with the existing diagnostic methods.

Clinical and economic analysis of patients with acute myeloid leukemia by FLT3 status and midostaurin use at a Comprehensive Cancer Center.

INTRODUCTION: Identification of cytogenetic and molecular abnormalities has become vital for the appropriate treatment of acute myeloid leukemia (AML). One of the most common molecular alterations in AML is the constitutive activation by internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3). METHODS: This observational, retrospective, cohort study at the Huntsman Cancer Institute (HCI) had two time periods: 1) a historical pre-midostaurin time period which consisted of the FLT3 mutated (FLT3m) and FLT3 wild type (FLT3wt) cohorts from January 1, 2007, to December 31, 2016, and 2) a post-midostaurin cohort which consisted of the FLT3 mutated midostaurin-user cohort (early mido) from May 01, 2017 to December 31, 2018. RESULTS: In total, 39 patients were included in the FLT3m cohort, 61 in the FLT3wt cohort, and seven in the early mido cohort. FLT3m patients spent fewer days in the hospital during the first consolidation regimen and received fewer consolidation cycles compared to FLT3wt patients. Overall survival (OS) was similar between FLT3m and FLT3wt patients. For patients without hematopoietic stem cell transplant, OS was significantly shorter for FLT3m patients compared to FLT3wt patients. Mean AML related inpatient charges and physician charges for FLT3m patients were significantly higher than FLT3wt patients. CONCLUSION: The FLT3 mutation is historically associated with a shorter time to transplant and increased total health care charges. More information is needed to evaluate the real-world treatment strategies for FLT3-mutated patients in the presence of FLT3 inhibitors and the impact of these treatment strategies on clinical and economic outcomes.

Acute Leukemia: Diagnosis and Treatment.

OBJECTIVE: To provide an overview of acute leukemia, comparing incidence, presenting symptoms, diagnosis, prognosis, and treatment of the major subtypes. DATA SOURCES: Review of articles dated 2010 to present in PubMed and CINAHL, and National Comprehensive Cancer Network Guidelines. CONCLUSION: The diagnosis of acute leukemia is comprised of a variety of hematopoietic neoplasms that are both complex and unique. Each subtype of acute leukemia has defining characteristics that affect prognosis and treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses play an integral role in the care of the patient with acute leukemia during and beyond hospitalization. Therefore, baseline knowledge of these diseases is essential. Early symptom recognition is central in the management of oncologic emergencies.

A favorable inductive remission rate for decitabine combined with chemotherapy as a first course in <60-year-old acute myeloid leukemia patients with myelodysplasia syndrome features.

In acute myeloid leukemia (AML), myelodysplasia-related changes contribute to a poor prognosis. This retrospective, propensity score-matched study analyzed 108 newly diagnosed AML patients with features of myelodysplasia syndrome (MDS) (aged 14-60 years) from 2014 to 2018, who received either idarubicin and cytarabine (IA) or decitabine, idarubicin and cytarabine (DAC+IA), and compared efficacy and toxicity between the two regimens. After propensity score matching, there were 54 patients in each group. The rate of complete remission (CR) was higher in the DAC+IA group than in the IA group (85.2% vs 68.5%, P = .040) after the first course, and toxicities were comparable in both groups. Multivariate analysis indicated that the combination with DAC was independent factor for CR rate after the first induction therapy (OR = 2.978, 95% CI:1.090-8.137, P = .033). Subgroup analysis showed a CR advantage for DAC+IA (vs IA) for patients of intermediate-high risk status according to National Comprehensive Cancer Network prognostic stratification. In conclusion, DAC+IA is therefore offered as a new induction choice for newly diagnosed AML patients with features of MDS, aged <60 years old, especially in intermediate-high risk status.

Pain in patients with newly diagnosed or relapsed acute leukemia.

PURPOSE: Acute leukemia (AL) is associated with substantial morbidity and mortality. We assessed the prevalence and correlates of pain in patients with newly diagnosed or relapsed AL. METHODS: Patients with newly diagnosed or relapsed AL admitted to a comprehensive cancer center completed the Memorial Symptom Assessment Scale (MSAS), which assesses prevalence, severity, and distress associated with pain and other symptoms. Factors associated with severe pain were assessed using logistic regression. Two raters completed chart reviews in duplicate for patients with severe pain (MSAS severity ≥ 3/4) to determine the site of pain. RESULTS: Three hundred eighteen patients were recruited from January 2008 to October 2013: 245 (77.0%) had acute myeloid or acute promyelocytic leukemia (AML/APL) and 73 (23.0%) had acute lymphoblastic leukemia (ALL); 289 (90.9%) were newly diagnosed and 29 (9.1%) had relapsed disease. Pain was reported in 156/318 (49.2%), of whom 55/156 (35.3%) reported severe pain (≥ 3/4). Pain was associated with all psychological symptoms (all p < 0.005) and some physical symptoms. Severe pain was associated with younger age (p = 0.02), worse performance status (p = 0.04), ALL diagnosis (p = 0.04), and time from onset of chemotherapy (p = 0.03), with pain peaking at 4 weeks after chemotherapy initiation. The most common sites of severe pain were oropharynx (22; 40%), head (12; 21.8%), and abdomen (11; 20%). Only 3 patients (0.9%) were referred to the symptom control/palliative care team during the month prior to or following assessment. CONCLUSIONS: Pain is frequent, distressing, and predictable in patients undergoing induction chemotherapy for AL. Further research is needed to assess the efficacy of early supportive care in this population.