Acute Myeloid Leukemia, Version 3.2023, NCCN Clinical Practice Guidelines in Oncology.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths from leukemias in the United States. Like AML, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a myeloid malignancy. It is a rare malignancy characterized by the aggressive proliferation of precursors of plasmacytoid dendritic cells that frequently involves the bone marrow, skin, central nervous system, and other organs and tissues. This discussion section focuses on the diagnosis and management of BPDCN as outlined in the NCCN Guidelines for AML.

The impact of bridging therapy prior to CD19-directed chimeric antigen receptor T-cell therapy in patients with large B-cell lymphoma.

In the relapsed/refractory setting for treatment of large B-cell lymphoma (LBCL), chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective treatment modality. Patients often have aggressive disease that requires prompt treatment in the form of bridging therapy (BT) for disease stabilisation while CAR-T cells are manufactured. Patients (n = 75) undergoing CAR-T therapy infusion for LBCL at our institution were identified. A total of 52 (69·3%) received BT and 23 (30·7%) received no BT (NBT). BT modalities included systemic BT (SBT) in 28 patients, radiation BT (RBT) in 14, and high-dose steroid BT (HDS) in 10. There was no difference in incidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome between BT and NBT (P = 0·18 and P = 0·53 respectively). Prolonged cytopenias at Day 180 were more common in BT than NBT (50% vs. 13·3%, P = 0·04). The SBT and RBT subgroups had more cytopenias at Day 180 compared to the HDS and NBT subgroups (58·3% and 57·1% vs. 20% and 13·3% respectively, P = 0·04). Disease response at last follow-up, progression-free survival and overall survival were similar between BT, NBT, and BT subgroups. In summary, BT can be safely considered in patients undergoing CAR-T therapy. However, those undergoing BT with SBT or RBT are at higher risk of prolonged cytopenias after CAR-T therapy.

Hospitalization and Post-hospitalization Outcomes Among Teaching Internal Medicine, Employed Hospitalist, and Locum Tenens Hospitalist Services in a Tertiary Center: a Prospective Cohort Study.

BACKGROUND: There are no prospective studies comparing hospitalization and post-hospitalization outcomes between teaching internal medicine services and non-teaching hospitalists, and no prospective studies comparing these outcomes between locum and employed hospitalists. OBJECTIVE: To compare the length of stay, hospital costs readmission rate, and mortality rate in patients treated by teaching internal medicine services vs. hospitalists and among patients treated by locum vs. employed hospitalists. DESIGN: Prospective cohort study. Propensity score was used to obtain weighted estimates. SETTING: Referral center. PATIENTS: All patients 18 years and older admitted to internal medicine services. INTERVENTION: Treatment by teaching internal medicine services vs. hospitalists. Treatment by locum hospitalists vs. employed hospitalists. MAIN MEASURES: Primary outcome was adjusted length of stay and secondary outcomes included hospital cost, inpatient mortality, 30-day all-cause readmission, and 30-day mortality. KEY RESULTS: A total of 1273 patients were admitted in the study period. The mean patient age was 61 ± 19 years, and the sample was 52% females. Teaching internal medicine physicians admitted 526 patients and non-teaching hospitalists admitted 747 patients. Being seen exclusively by teaching internal medicine physicians comports with a shorter adjusted hospital stay by 0.6 days (95% CI - 1.07 to - 0.22, P = .003) compared to non-teaching hospitalists. Adjusted length of stay was 1 day shorter in patients seen exclusively by locums compared to patients seen exclusively by employed services (95% CI - 1.6 to - 0.43, P < .001) with an adjusted average hospital cost saving of 1339 dollars (95% CI - 2037 to - 642, P < .001). There was no statistically significant difference in other outcomes. CONCLUSIONS: Teaching internal medicine services care was associated with a shorter stay but not with increased costs, readmission, or mortality compared to non-teaching services. In contrary to the "expected," patients treated by locums had shorter stays and decreased hospital costs but no increase in readmissions or mortality.

Hospital admission trends due to respiratory diseases in England and Wales between 1999 and 2019: an ecologic study.

BACKGROUND: Identifying trends of hospital admissions for respiratory diseases is crucial for public health and research to guide future clinical improvements for better outcomes. This study aims to define the trends of respiratory disease-related hospital admissions (RRHA) in England and Wales between 1999 and 2019. METHODS: An ecological study was conducted using hospital admission data taken from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Hospital admissions data for respiratory diseases were extracted for the period between April 1999 and March 2019. The trend in hospital admissions was assessed using a Poisson model. RESULTS: Hospital admission rate increased by 104.7% [from 1535.05 (95% CI 1531.71-1538.38) in 1999 to 3142.83 (95% CI 3138.39-3147.26) in 2019 per 100,000 persons, trend test, p < 0.01]. The most common causes were influenza and pneumonia, chronic lower respiratory diseases, other acute lower respiratory infections, which accounted for 26.6%, 26.4%, and 14.9%, respectively. The age group 75 years and above accounted for 34.1% of the total number of hospital admissions. Males contributed to 50.5% of the total number of hospital admissions. Hospital admission rate in females increased by 119.8% [from 1442.18 (95% CI 1437.66-1446.70) in 1999 to 3169.38 (95% CI 3163.11-3175.64) in 2019 per 100,000 persons, trend test, p < 0.001]. Hospital admission rate increased by 92.9% in males [from 1633.25 (95% CI 1628.32-1638.17) in 1999 to 3149.78 (95% CI 3143.46-3156.09) in 2019 per 100,000 persons, trend test, p < 0.001]. CONCLUSION: During the study period, hospital admissions rate due to respiratory diseases increased sharply. The rates of hospital admissions were higher among males for the vast majority of respiratory diseases. Further observational studies are warranted to identify risk factors for these hospital admissions and to offer relevant interventions to mitigate the risk.

Comparative Effectiveness of Busulfan and Fludarabine versus Fludarabine and 400 cGy Total Body Irradiation Conditioning Regimens for Acute Myeloid Leukemia/Myelodysplastic Syndrome.

Allogeneic hematopoietic cell transplantation conditioning regimen intensity has varied for patients with acute myeloid leukemia and myelodysplastic syndrome. A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus those of fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 received FluTBI. The BuFlu group received more red blood cell transfusions (P = .02) and had a longer time to platelet recovery (P = .004). There were no differences between the regimens regarding incidence of acute or chronic graft-versus-host disease (GVHD), quality of life, or 2-year outcome estimates for relapse (48; 95% confidence interval [CI], 30 to 64 and 50; 95% CI, 33 to 65), nonrelapse mortality (29; 95% CI, 14 to 45 and 29; 95% CI, 15 to 44), relapse-free survival (27; 95% CI, 13 to 43 and 29; 95% CI, 16 to 44), and overall survival (35; 95% CI, 19 to 51; and 37; 95% CI, 22 to 52), respectively. These comparable outcomes have implications for health care resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and additional strategies to prevent relapse and limit toxicities as well as cost-effectiveness analyses are warranted.

Long-term peripheral neuropathy symptoms in breast cancer survivors.

PURPOSE: Peripheral neuropathy (PN) is a common and distressing complication from chemotherapy. Symptoms often, but not always, improve with time. The prevalence of long-term PN symptoms in breast cancer survivors is not well known. We sought to explore PN symptoms and associated risk factors among breast cancer survivors at least 2 years out from diagnosis. METHODS: We performed a cross-sectional retrospective study investigating the prevalence of patient-reported numbness, tingling, and anesthesia symptoms as a surrogate for PN in breast cancer survivors. We included patients with stage 0-III breast cancer who completed a clinical questionnaire at a survivorship visit that occurred 2 or more years after diagnosis. We estimated the prevalence of PN and identified risk factors for PN. RESULTS: Six hundred and five patients assessed between April 2009 and October 2016 met eligibility for analysis. Median age was 60 years. Median number of years from diagnosis to assessment was 6.3. All patients had surgery and 62% had chemotherapy. Twenty-seven percent reported PN. On univariable analysis, obesity, stage II and III, mastectomy, PN before diagnosis, and receipt of taxane chemotherapy were associated with higher risk of PN (all p < 0.05); older age, exercise, ER-positive disease, and endocrine therapy were associated with lower risk of PN (all p < 0.05). On multivariable analysis, only receipt of docetaxel (OR 2.18, CI 1.22-3.88) or paclitaxel (OR 4.07, CI 2.54-6.50) and reporting PN symptoms before diagnosis (OR 3.28, CI 1.49-7.21) were associated with higher risk of PN. Overall, 17, 20, 31, and 44% reported long-term PN symptoms after no chemotherapy, non-taxane chemotherapy, docetaxel chemotherapy, and paclitaxel chemotherapy, respectively. CONCLUSION: Long-term peripheral neuropathy symptoms are reported by a significant minority of breast cancer survivors, particularly following paclitaxel or docetaxel chemotherapy. These study findings can help inform patients and clinicians regarding long-term PN risk following chemotherapy.

Spontaneous subdural hematoma in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia with normal platelet count after dasatinib treatment.

Dasatinib, which is an inhibitor of BCR-ABL and SRC family tyrosine kinases, is used for the treatment of patients with Philadelphia chromosome (Ph) positive leukemia, especially for those who develop resistance or who are intolerant to imatinib. The most common adverse effects attributed to its use are: myelosuppression, nausea, diarrhea, and peripheral edema. Hemorrhage, which could be gastrointestinal, genitourinary or central nervous system, is a less frequent adverse effect. In this case, we report a patient affected by precursor B-cell acute lymphoblastic leukemia (ALL) positive for the Ph chromosome translocation treated with the tyrosine kinase inhibitor (TKI) dasatinib. During the treatment with dasatinib the patient developed subdural hematoma (SDH). She did not have any head trauma, thrombocytopenia, coagulopathy or meningeal involvement, making dasatinib-induced platelet dysfunction the most likely cause of SDH.

The prevalence of isolated growth hormone deficiency among children of short stature in Jordan and its relationship with consanguinity.

OBJECTIVE: The prevalence of isolated growth hormone deficiency (IGHD) among short-statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short-statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity. DESIGN: We conducted a 24-month cross-sectional observational trial at an outpatient tertiary care center in Amman, Jordan. PATIENTS: We obtained detailed family histories, medical evaluations and laboratory tests for 94 short-statured children (50 boys and 44 girls aged 6-16 years). MEASUREMENTS: Complete and partial GHD were defined as peak GH responses of 5 and 7 µg/l (15 and 21 mIU/l) [IRMA/DiaSorin®], respectively, in both exercise and insulin tolerance tests. RESULTS: GHD was diagnosed in 69·1% of the short children, including 86% (43/50) of the children of consanguineous parents (83·3%, 93·8% and 81·8% of children of first cousins, first cousins once removed and second cousins, respectively) and 50% (20/44) of the children of nonconsanguineous parents (P = 0·039, 0·002 and 0·013, respectively). However, there was no statistically significant difference in the prevalence of small pituitary MRI between GH-deficient children of consanguineous parents and those of nonconsanguineous parents (28·6% vs 13·6%, P = 0·3). CONCLUSIONS: The prevalence of IGHD among referred short children in Jordan was exceptionally high and significantly higher in the children of CM. In countries where CM is common, preconception counselling and rigorous surveillance for GHD in short children may be indicated.

Large Granular Lymphocytic Leukemia: Clinical Features, Molecular Pathogenesis, Diagnosis and Treatment.

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disorder characterized by persistent clonal expansion of mature T- or natural killer cells in the blood via chronic antigenic stimulation. LGL leukemia is associated with specific immunophenotypic and molecular features, particularly STAT3 and STAT5 mutations and activation of the JAK-STAT3, Fas/Fas-L and NF-κB signaling pathways. Disease-related deaths are mainly due to recurrent infections linked to severe neutropenia. The current treatment is based on immunosuppressive therapies, which frequently produce unsatisfactory long-term responses, and for this reason, personalized approaches and targeted therapies are needed. Here, we discuss molecular pathogenesis, clinical presentation, associated autoimmune disorders, and the available treatment options, including emerging therapies.

Navigating The 2022 International Consensus and World Health Organization Classifications of Hematopathology: A Call for Unified Diagnostic Language.

CONTEXT.­: In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications. OBJECTIVE.­: To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States. DESIGN.­: An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media. RESULTS.­: A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas. CONCLUSIONS.­: Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.

Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3ß Activation and c-Myc and Mcl-1 Proteasomal Degradation.

Acute myeloid leukemia (AML) with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) has poor outcomes. FLT3-ITD drives constitutive and aberrant FLT3 signaling, activating STAT5 and upregulating the downstream oncogenic serine/threonine kinase Pim-1. FLT3 inhibitors are in clinical use, but with limited and transient efficacy. We previously showed that concurrent treatment with Pim and FLT3 inhibitors increases apoptosis induction in FLT3-ITD-expressing cells through posttranslational downregulation of Mcl-1. Here we further elucidate the mechanism of action of this dual targeting strategy. Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD-expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. Pim inhibitor and gilteritinib cotreatment increased apoptosis induction, produced synergistic cytotoxicity, downregulated c-Myc protein expression, earlier than Mcl-1, increased turnover of both proteins, which was rescued by proteasome inhibition, and increased efficacy and prolonged survival in an in vivo model. Gilteritinib and Pim inhibitor cotreatment of Ba/F3-ITD cells infected with T58A c-Myc or S159A Mcl-1 plasmids, preventing phosphorylation at these sites, did not downregulate these proteins, increase their turnover or increase apoptosis induction. Moreover, concurrent treatment with gilteritinib and Pim inhibitors dephosphorylated (activated) the serine/threonine kinase glycogen synthase kinase-3ß (GSK-3ß), and GSK-3ß inhibition prevented c-Myc and Mcl-1 downregulation and decreased apoptosis induction. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3ß as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3ß activation as a therapeutic strategy in FLT3-ITD AML. SIGNIFICANCE: FLT3-ITD is present in 25% of in AML, with continued poor outcomes. Combining Pim kinase inhibitors with the FDA-approved FLT3 inhibitor gilteritinib increases cytotoxicity in vitro and in vivo through activation of GSK-3ß, which phosphorylates and posttranslationally downregulates c-Myc and Mcl-1. The data support efficacy of GSK-3ß activation in FLT3-ITD AML, and also support development of a clinical trial combining the Pim inhibitor TP-3654 with gilteritinib.

Institutional disparities in the distribution of the American Society of Clinical Oncology grants.

BACKGROUND: Disparities in academia are increasingly recognized, but what has historically been underrecognized is the cancer institutional disparities in the distribution of grants. We sought to characterize grants awarded by the American Society of Clinical Oncology (ASCO) ove the last 38 year with focus on grants awarded for career development and professional growth. METHODS: We used ASCO online database that contains grant and award recipients (1984-December 2021). We included all grants that were awarded for more than one year with $10,000 or more in annual funds. RESULTS: More than a third (38%) of all the individual grants were awarded for researchers from four institutions. Career development awards and young investigator awards were awarded for investigators of whom two-thirds were affiliated with a university in one of five states. CONCLUSION: There is a significant concentration of grants awarded to oncology investigators from a few institutions including grant focused on professional growth (Career development awards and young investigator awards) POLICY STATEMENT: Institutions such as ASCO may need to facilitate awarding grants and/or providing external mentorship for institutions with low number of previous grants, especially for career development and young investigator grants to help in resolving the current institutional disparities.

Impact of KRAS and NRAS mutations on outcomes in acute myeloid leukemia.

The prognostic significance of RAS mutations in AML is poorly understood. In this ambispective cohort study of 239 newly-diagnosed AML patients at the University of Maryland, we assessed the median overall survival (mOS) and median event-free survival (mEFS) in RAS wild-type (WT) AML (n = 196), KRAS-mutated AML (n = 11), NRAS-mutated AML (n = 25), and KRAS/NRAS-mutated AML (n = 7). We used propensity score to adjust outcomes. NRAS-mutated AML had a similar response rate to first-line treatment and mOS compared to RAS-WT AML (57 vs. 54%, p = 0.8, 22.7 vs. 14.6 months, p = 0.7). The mOS of KRAS-mutated AML was shorter compared to RAS-WT AML (p = 0.049) and NRAS-mutated AML (p = 0.02). KRAS-mutated AML treated with anthracycline-based first-line regimens had a lower relative mortality compared to treatment with hypomethylating agents with venetoclax (HR <0.01, p = 0.04) and without venetoclax (HR <0.01, p = 0.04). This study demonstrates that KRAS but not NRAS mutations are associated with worse outcomes in AML.NOVELTY STATEMENTWhat is the new aspect of your work? The clinical significance of RAS mutations remains poorly defined and prior studies have yielded conflicting results. We used causal inferential methods, propensity score modeling, to determine the impact of KRAS and NRAS mutation on survival in newly diagnosed AML patients, independent of other risk factors. Moreover, we analyzed the outcomes of KRAS and NRAS-mutated AML patients receiving first-line therapy with hypomethylating agents and other non-anthracycline-based regimens. We provided a detailed description of RAS-mutated AML, including co-occurring mutations and cytogenetic abnormalities.What is the central finding of your work? KRAS mutations but not NRAS mutations in AML are directly linked to worse outcomes even after controlling for differences in AML type, co-occurring cytogenetic changes, treatment regimens, and comorbidities. KRAS-mutated AML has a higher relative mortality when treated with a hypomethylating agent-based first-line induction regimen compared to treatment with an anthracycline-based regimen.What is (or could be) the specific clinical relevance of your work? Our findings can help refine our genetic profiles of AML, improve prognostic models, and better stratify treatment regimens.

The Trend of Combined Modality Treatment and its Outcomes in Elderly Patients With Primary CNS Lymphoma: A 12-year Population-based Analysis Using Propensity Score.

BACKGROUND/AIM: The addition of radiation to chemotherapy in elderly patients with primary central nervous system lymphoma (PCNSL) remains controversial. This aim of this study was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients. PATIENTS AND METHODS: We identified 6,537 patients who received single treatment modality, CMT, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes. RESULTS: Only 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with an APC of -6.0% (95%CI=-8.0 - -4.0, p-value <0.001) during the 12 years. Apart from classical prognostic factors (age and comorbidities), treatment selection was significantly influenced by sex, facility type, degree of urbanization, and type of insurance. CMT had improved survival [median overall survival 19.5 months (95%CI=15.7-22.8)] compared with single-modality treatment. This effect was more prominent in the first year. CONCLUSION: Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival.

Patterns of treatment and their outcomes in primary breast lymphoma; a comprehensive population-based analysis.

BACKGROUND: Primary breast lymphoma (PBL) is managed differently among centers, using surgery, systemic therapy and/or radiation. With data derived from the National Cancer Database (NCDB), we aim to describe treatments utilized in the United States, estimate the overall survival (OS) of different therapeutic modalities and determine the role of systemic therapy in patients with PBL. METHODS: We conducted a retrospective cohort study using de-identified data from the NCDB. The NCDB provided records of 4616 patients diagnosed with PBL between 2004 and 2015. We excluded patients diagnosed with HIV, with no survival data, not treated in the reporting facility, without histologic confirmation, with stage III/ IV disease and for whom surgery, radiation, or systemic therapy was contraindicated. Both propensity score weighting and Cox models were used to obtain adjusted estimates. Based on histopathology, PBL was classified into indolent (I-PBL) and aggressive (A-PBL). RESULTS: In a sample size of 2063 PBL patients, the median age was 67 years (interquartile range (IQR): 57-78), and 97% were females. In 1027 patients with I-PBL, the median follow-up was 66 months (95% confidence interval (CI): 32.6-107.2) and 60% of patients had extranodal marginal zone subtype. Systemic therapy did not improve adjusted-OS (median: 154 vs. 143 months, P = 0.36) (Hazard ratio (HR): 0.86, 95% CI: 0.60-1.25, P = 0.42). The treatment arms associated with the highest adjusted 5-year OS were as follows: radiation (85%), surgery (79%), systemic & radiation (87%) and radiation & surgery (87%) (P = 0.9). In 1036 patients with A-PBL, the median follow-up was 67.4 months (95% CI: 35.9-105), and 87% of patients had diffuse large B-cell subtype. Patients with A-PBL who received systemic therapy had an improved adjusted-OS (median: 115 vs. 72 months, P < 0.01) (HR: 0.45, 95% CI: 0.38-0.53, P < 0.001). The treatment arms associated with the highest adjusted 5-year OS were: systemic (69%), systemic & radiation (77%), systemic & radiation & surgery (79%) and systemic & surgery (79%) (P = 0.4). CONCLUSIONS: Systemic therapy used as first-line treatment is essential in A-PBL. Local therapy in the I-PBL using surgery and/or radiation is effective in long-term disease control. There is significant variation in front-line treatment modalities utilized in PBL across the US, many associated with similar outcomes.

Trends in Hospital Admissions Due to Neoplasms in England and Wales between 1999 and 2019: An Ecological Study.

Objectives: This study aimed to investigate the trends in neoplasm-related hospital admissions (NRHA) in England and Wales between 1999 and 2019. Methods: This is an ecological study using publicly available data taken from the two main medical databases in England and Wales; the Hospital Episode Statistics database in England and the Patient Episode Database in Wales. Hospital admissions data were collected for the period between April 1999 and March 2019. Results: A total of 35,704,781 NRHA were reported during the study period. Females contributed to 50.8% of NRHA. The NRHA rate among males increased by 50.0% [from 26.62 (95% CI 26.55−26.68) in 1999 to 39.93 (95% CI 39.86−40.00) in 2019 per 1000 persons, trend test, p < 0.001]. The NRHA rate among females increased by 44.1% [from 27.25 (95% CI 27.18−27.31) in 1999 to 39.25 (95% CI 39.18−39.32) in 2019 per 1000 persons, trend test, p < 0.001]. Overall, the rate of NRHA rose by 46.2% [from 26.93 (95% CI 26.89−26.98) in 1999 to 39.39 (95% CI 39.34−39.44) in 2019 per 1000 persons, trend test, p < 0.001]. Conclusion: Hospital admission rates due to neoplasms increased between 1999 and 2019. Our study demonstrates a variation in NRHA influenced by age and gender. Further observational studies are needed to identify other factors associated with increased hospital admissions among patients with different types of neoplasms.

Consolidative Autologous Stem Cell Transplantation Versus Whole Brain Radiation in PCNSL; a Nationwide Analysis.

BACKGROUND: The best consolidation strategy after induction chemotherapy in Primary CNS Lymphoma (PCNSL) remains controversial. Our objective is to estimate the overall survival (OS) for autologous stem cell transplantation (ASCT) versus whole brain radiation (WBRT) in the consolidation setting. We also sought to evaluate the factors affecting treatment selection METHODS: We identified 1620 patients with PCNSL who received chemotherapy followed by either ASCT or WBRT between 2004 and 2015 from the National Cancer Database. A propensity score weighting methodology was used to compare survival outcomes. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of ASCT use. RESULTS: Only 12.2% of patients received ASCT, and this proportion rose steadily between 2004 and 2015, with APC of +23%. Treatment selection was affected by age, type of area, distance from the treating facility, and level of education. With a median follow-up of 68.4 months, adjusted-median OS was 91.4 months and not reached for WBRT and ASCT groups, respectively (P < .001). 5-year OS was 74.4% in the ASCT group versus 58.7% in the WBRT group (HR 0.40, 95% CI 0.27-0.60, P -value < .01). CONCLUSION: Socioeconomic factors affect the selection of consolidative treatment in patients with PCNSL which can alter outcomes. Frequency of consolidative ASCT is increasing for patients with PCNSL. This is the first and largest cohort study, to our knowledge, to show an OS advantage in favor of ASCT. This OS benefit needs to be confirmed in a randomized controlled fashion.

A Focus on Intermediate-Risk Acute Myeloid Leukemia: Sub-Classification Updates and Therapeutic Challenges.

Acute myeloid leukemia (AML) represents a heterogeneous group of hematopoietic neoplasms deriving from the abnormal proliferation of myeloid progenitors in the bone marrow. Patients with AML may have highly variable outcomes, which are generally dictated by individual clinical and genomic characteristics. As such, the European LeukemiaNet 2017 and 2022 guidelines categorize newly diagnosed AML into favorable-, intermediate-, and adverse-risk groups, based on their molecular and cytogenetic profiles. Nevertheless, the intermediate-risk category remains poorly defined, as many patients fall into this group as a result of their exclusion from the other two. Moreover, further genomic data with potential prognostic and therapeutic influences continue to emerge, though they are yet to be integrated into the diagnostic and prognostic models of AML. This review highlights the latest therapeutic advances and challenges that warrant refining the prognostic classification of intermediate-risk AML.

Outcomes of Newly Diagnosed Acute Myeloid Leukemia Patients Treated With Hypomethylating Agents With or Without Venetoclax: A Propensity Score-Adjusted Cohort Study.

There is a deficiency of real-world data on the impact of combining venetoclax (VEN) with hypomethylating agents (HMAs) in newly diagnosed acute myeloid leukemia (AML) patients. We conducted a single-center, propensity-adjusted retrospective cohort study to compare composite complete remission (CCR) rates, median overall survival (m-OS) and median event-free survival (m-EFS). A total of 170 adult AML patients were treated with first-line azacitidine (AZA) or decitabine (DEC) +/- VEN. Median age was 71 years and 99 (58%) were male. Median follow-up in HMA and HMA-VEN groups was 79 and 21 months. Treatments included AZA alone (n=35, 21%), DEC alone (n=84, 49%), AZA-VEN (n=24, 14%) and DEC-VEN (n=27, 16%). VEN improved CCR rates to HMAs overall (52% vs. 27%, P<0.05) and to AZA (54% vs. 10%, P<0.05), but not to DEC (43% vs. 32%, P=0.35); it did not improve OS, and only improved EFS for AZA (10.5 vs. 3.8 months, P<0.05). CCR rates were lower with AZA than with DEC (13% vs. 33%, P<0.05), but OS and EFS were not different statistically. CCR rates did not differ for AZA-VEN vs. DEC-VEN (CCR: 58% vs. 52%, P=0.66), but OS and EFS were longer for AZA-VEN (m-OS: 12.3 vs. 2.2 months, P<0.05; m-EFS: 9.2 vs. 2.1 months, P<0.05). Our analysis showed that combining VEN with AZA in newly diagnosed AML patients improved outcomes, but combining VEN with DEC did not. AZA-VEN was associated with improved outcomes compared to DEC-VEN. Further studies are needed to test the benefit of combining VEN with DEC.