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Background: Given the geographical sparsity of Rare Diseases (RDs), assembling a cohort is often a challenging task. Common data models (CDM) can harmonize disparate sources of data that can be the basis of decision support systems and artificial intelligence-based studies, leading to new insights in the field. This work is sought to support the design of large-scale multi-center studies for rare diseases. Methods: In an interdisciplinary group, we derived a list of elements of RDs in three medical domains (endocrinology, gastroenterology, and pneumonology) according to specialist knowledge and clinical guidelines in an iterative process. We then defined a RDs data structure that matched all our data elements and built Extract, Transform, Load (ETL) processes to transfer the structure to a joint CDM. To ensure interoperability of our developed CDM and its subsequent usage for further RDs domains, we ultimately mapped it to Observational Medical Outcomes Partnership (OMOP) CDM. We then included a fourth domain, hematology, as a proof-of-concept and mapped an acute myeloid leukemia (AML) dataset to the developed CDM. Results: We have developed an OMOP-based rare diseases common data model (RD-CDM) using data elements from the three domains (endocrinology, gastroenterology, and pneumonology) and tested the CDM using data from the hematology domain. The total study cohort included 61,697 patients. After aligning our modules with those of Medical Informatics Initiative (MII) Core Dataset (CDS) modules, we leveraged its ETL process. This facilitated the seamless transfer of demographic information, diagnoses, procedures, laboratory results, and medication modules from our RD-CDM to the OMOP. For the phenotypes and genotypes, we developed a second ETL process. We finally derived lessons learned for customizing our RD-CDM for different RDs. Discussion: This work can serve as a blueprint for other domains as its modularized structure could be extended towards novel data types. An interdisciplinary group of stakeholders that are actively supporting the project's progress is necessary to reach a comprehensive CDM. Conclusion: The customized data structure related to our RD-CDM can be used to perform multi-center studies to test data-driven hypotheses on a larger scale and take advantage of the analytical tools offered by the OHDSI community. [ABSTRACT FROM AUTHOR]

Introduction: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics. Methods: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012 and 2022 that were phase 1, 2, or 3 and relevant trial characteristics were extracted. Results: 1,270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p < 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p < 0.01). Phase 3 trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase 1 and 2 trials that had higher rates of excluding patients with only active CNS involvement (p < 0.01). Conclusion: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active but also with any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials. [ABSTRACT FROM AUTHOR]

We evaluated outcomes of AML patients with central nervous system (CNS) involvement at two academic institutions. Fifty-two adult patients were identified. Neurologic symptoms were reported in 69% of patients, with headache the most common (33%). 84% (n = 42) of patients cleared their cerebrospinal fluid (CSF), with a median number of one dose of intrathecal (IT) chemotherapy. Of these patients, 21% (n = 9) had a CSF relapse, with 67% (n = 6) of those experiencing CSF relapse also having concurrent bone marrow relapse. Of the 36 patients with baseline neurologic symptoms, 69% had improvement in symptoms post-IT therapy. The median overall survival was 9.3 months and 3.5 months for patients with CNS involvement diagnosed before/during induction and at relapse, respectively. In this study, IT therapy was rapidly effective in clearing CSF blasts and improving neurologic symptoms in most patients. Few patients experienced CSF relapse, which predominantly occurred in the setting of concomitant bone marrow relapse. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are devastating diseases that frequently rely on the use of parenteral hypomethylating agents (HMAs), either as monotherapy or in combination, as first-line treatment for many patients. Two new oral HMAs, decitabine/cedazuridine (DC) for use in place of azacitidine or decitabine in MDS, and azacitidine (CC-486) for use as maintenance treatment in AML, were recently approved by the FDA. We will discuss the development of these oral HMAs, including the advantages/disadvantages in transitioning to oral HMAs and an in depth look at the pivotal phase III trials that led to their FDA approval – ASCERTAIN for DC and QUAZAR-AML-001 for CC-486. We also review how these agents have been and are being studied in other malignancies, and examine the future role that these exciting novel agents will play in both MDS and AML. [ABSTRACT FROM AUTHOR]

Treatment options are limited for patients with advanced forms of myeloproliferative neoplasms (MPN) including blast-phase disease (MPN-BP). Decitabine has frequently been deployed but its efficacy and safety profile are not well described in this population. We retrospectively reviewed 42 patients treated with decitabine either alone or in combination with ruxolitinib at our institution: 16 with MPN-BP, 14 with MPN accelerated-phase (MPN-AP), and 12 with myelofibrosis with high-risk features (MF-HR). The median overall survival (OS) for the MPN-BP patients was 2.6 months, and for those who received ≥2 cycles of decitabine therapy, it was 6.7 months (3.8–29.8). MPN-BP patients with a poor performance status and who required hospitalization at the time of the initiation of decitabine had a dismal prognosis. After a median follow-up of 12.4 months for MPN-AP patients, and 38.7 months for MF-HR patients, the median OS was not reached for either cohort, with 1 and 2 patients alive at 60 months, respectively. The probability of spleen length reduction and transfusion independence within 12 months of initiating decitabine was 28.6 and 23.5%, respectively. The combination of decitabine and ruxolitinib appeared to improve overall survival versus single-agent decitabine (21 and 12.9 months, respectively). Decitabine, alone or in combination with ruxolitinib, appears to have clinical benefit for patients with advanced phases of MPN when initiated early in the disease course prior to the development of MPN-BP. [ABSTRACT FROM AUTHOR]

This article is a response to a commentary on the challenges of identifying blasts in cerebrospinal fluid (CSF) specimens from patients with acute myeloid leukemia (AML). The authors agree with the challenges identified by the commentator, including the high false negative rate and the use of instruments designed for other specimen types. They describe their own laboratory practices, such as prioritizing immediate processing of CSF samples and collaborating with hematopathologists and cytologists for accurate identification. The authors also discuss the need for standardization in screening protocols and diagnostic criteria for CNS involvement in AML. [Extracted from the article]

Acute promyelocytic leukemia (APL) is a particularly aggressive subtype of acute myeloid leukemia (AML), with high rates of early death. It is important to examine how epidemiological characteristics, clinical and treatment factors, cytogenetic and genetic data affect survival and differ between APL and non-APL AML patients. We analyzed population data from the New York State Cancer Registry to characterize AML including APL incidence rates by demographics. APL incidence rates were higher among Hispanics than non-Hispanics [incidence rate ratio = 1.22; 95% confidence interval (CI) = 1.02–1.43]; and among foreign-born than USA-born persons. APL incidence rates increased more rapidly through 1995–2014 than non-APL AML; and its frequency increased faster among foreign-born persons. In a hospital cohort of 390 AML patients, the risk of death was significantly higher among APL patients with FLT3-internal tandem duplications than those without [hazard ratio (HR) = 11.74; 95% CI = 1.03–134.5]; and among APL patients with secondary versus de novo disease (HR = 17.32; 95% CI = 1.56–192.1). Among non-APL AML patients, risk of death was significantly associated with prior chemotherapy with antitubulin agents after adjusting for age, gender and ethnicity (adjusted HR = 3.30; 95% CI = 1.49–7.32); and separately with older age, unfavorable cytogenetics and complex karyotype. This study highlights FLT3 -internal tandem duplications as a prognostic factor in APL and proposes consideration of prior antitubulin therapy as a prognostic factor in non-APL AML. [ABSTRACT FROM AUTHOR]

Graphical abstract [ABSTRACT FROM AUTHOR]

in this article, the author talks about how acute myeloid leukemia (AML) is a hematologic malignancy that disproportionately affects the elderly and is almost universally fatal. It also mentions how clinicians caring for patients with AML are often faced with the decision whether to continue hypomethylating agents (HMAs) therapy while hospitalized or encourage hospice enrollment.

Background In the era of increased antibiotic resistance, minimizing the use of broad-spectrum antibiotics is essential. We sought to determine whether there was a difference in risk of recurrent fever in patients with acute myelogenous leukemia (AML) and neutropenic fever without an identifiable source in which antibacterials were de-escalated prior to neutrophil recovery compared with those that continued until recovery. Methods We performed a retrospective chart review of adult patients with AML undergoing induction chemotherapy at Mount Sinai Hospital in New York, NY from 2009–2017. Neutropenic fever was defined as a temperature of 100.4°F for 1 hour or single temperature of 101°F in a patient with an absolute neutrophil count (ANC) of less than 500 cells/μL. Febrile patients were treated with cefepime, piperacillin–tazobactam, or a carbapenem. De-escalation was defined as changing from one of these antibiotics to antibacterial prophylaxis such as levofloxacin, or discontinuing antibiotics. The primary outcome was recurrent neutropenic fever. Secondary outcomes were adverse events related to antibiotics, intensive care unit (ICU) transfer, and all-cause mortality. Results Of 390 AML patients undergoing induction chemotherapy, 135 had a neutropenic fever; of whom, 77 had no identifiable infectious source. Of those 77, 38 had antibiotics de-escalated prior to ANC recovery ("short") and 39 had antibiotics continued until ANC recovery or discharge ("long"). Demographics were similar (Table 1). The median number of antibiotic days for the first fever was 9 in the short group and 15 in the long group (P = 0.0008) (Table 2). Risk of recurrent fever was 46% lower in the short group compared with the long group (hazard ratio 0.54, 95% CI: 0.34–0.88; P = 0.01). There was no significant difference in ICU transfer (P = 0.11) and in-hospital mortality (P = 0.36) between the short and long groups (Table 2). There were 7 adverse drug outcomes, 2 in the short group and 5 in the long group (Table 3). Conclusion Antibiotic de-escalation in AML patients with neutropenic fever with no identifiable infectious source was associated with a lower rate of recurrent fever without affecting ICU transfer, adverse drug events, and death. Physicians should consider de-escalation prior to ANC recovery in the appropriate setting. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses trends in the location of death for individuals with acute myeloid leukemia (AML) in the United States. The authors analyzed death certificates from 2003 to 2020 and found that deaths at home and in hospice increased over time, while hospital and outpatient deaths decreased. They also identified sociodemographic factors associated with the location of death, including age, sex, race, ethnicity, marital status, and education. The authors emphasize the importance of individualizing end-of-life care based on each patient's values and goals, and highlight disparities in care based on race. They suggest the need for further research on cultural differences in end-of-life preferences. The study provides statistical data on the location of death for AML patients and suggests policy changes to improve end-of-life care. However, it acknowledges limitations in the data and the need for qualitative information about individuals' preferences. [Extracted from the article]

Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication. • Data surrounding outcomes of CNS involvement in AML is generally sparse and inconsistent in the literature. • This meta analysis demonstrates that overall survival for AML patients with CNS involvement is inferior compared to patients without CNS involvement. • CNS involvement in AML should be viewed as a negative prognostic factor when evaluating patients with AML. • Attention should be made to ensure prompt identification and optimal treatment strategies to overcome this complication. [ABSTRACT FROM AUTHOR]