Care Patterns and Barriers to Outpatient Care for Adults With AML Following Intensive Chemotherapy at NCCN Member Institutions.

BACKGROUND: Prolonged hospitalization following intensive (re)induction chemotherapy for acute myeloid leukemia (AML), while standard, is costly and resource intense, limits inpatient bed capacity, and negatively impacts quality of life. Early hospital discharge (EHD) following completion of chemotherapy has proven safe as an alternative at select institutions, but is not widely implemented. PATIENTS AND METHODS: From February 2023 through May 2023, the NCCN Best Practices Committee conducted a survey evaluating AML hospitalization patterns, care models, and barriers to EHD at its 33 member institutions. RESULTS: A total of 30 (91%) institutions completed the survey; two-thirds treat >100 patients with AML annually and 45% treat more than half of these with intensive chemotherapy. In the (re)induction setting, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% aim to discharge patients after completion of chemotherapy if medically stable and logistically feasible. The predominant reasons for the perceived need for ongoing hospitalization were high risk of infection, treatment toxicities, and lack of nearby/accessible housing. There was no significant association between ability to practice EHD and annual AML volume or treatment intensity patterns (P=.60 and P=.11, respectively). In contrast, in the postremission setting, 87% of centers support patients following chemotherapy in the outpatient setting unless toxicities arise requiring readmission. Survey responses showed that 80% of centers were interested in exploring EHD after (re)induction but noted significant barriers, including accessible housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%), and limited bed availability for rehospitalization (50%). CONCLUSIONS: Hospitalization and care patterns following intensive AML therapy vary widely across major US cancer institutions. Although only 20% of surveyed centers practice EHD following intensive (re)induction chemotherapy, 87% do so following postremission therapy. Given the interest in exploring the EHD approach given potential advantages of EHD for both patients and health care systems, strategies to address identified medical and logistical barriers should be explored.

Hyper-CVAD versus dose-adjusted EPOCH as initial treatment for adults with acute lymphoblastic leukemia.

OBJECTIVES: We recently performed a single-arm phase II trial of DA-EPOCH in adults with acute lymphoblastic leukemia (ALL). We sought to compare these results to those with standard Hyper-CVAD. METHODS: We created a retrospective matched cohort of patients who received Hyper-CVAD (n = 69) at our center and otherwise met eligibility criteria for the DA-EPOCH trial (n = 53). RESULTS: Our outcomes support the use of Hyper-CVAD over DA-EPOCH in Ph- disease for both overall survival (OS; HR 0.18, p = .004) and event-free survival (EFS; HR 0.51, p = .06). In contrast, outcomes were similar in Ph+ disease (OS HR 0.97, p = .96; EFS HR 0.65, p = .21). Rates of morphologic remission and measurable residual-disease negativity were similar between the regimens. Hyper-CVAD was associated with significantly more febrile neutropenia (OR 1.9, p = .03) and a greater incidence of Grade 4 or 5 adverse events (20% vs. 6%). Average transfusions per cycle of both red blood cells (p < .001) and platelets (p < .001) were five-fold higher with Hyper-CVAD. CONCLUSIONS: Our findings support continued use of Hyper-CVAD for Ph- ALL but suggest that DA-EPOCH may be a reasonable alternative for Ph+ ALL. These data also highlight a potential role for DA-EPOCH in resource-limited settings or when more intense therapy is not feasible.

Cerebrospinal fluid flow cytometry and risk of central nervous system relapse after hyperCVAD in adults with acute lymphoblastic leukemia.

BACKGROUND: Potential involvement of the central nervous system (CNS) by acute lymphoblastic leukemia is typically evaluated by a conventional cytospin (CC) of cerebrospinal fluid (CSF). Multiparameter flow cytometry (MFC) is generally more sensitive and specific than morphology, but data to guide its use versus CC are limited. METHODS: This study identified 92 patients who had MFC performed on their initial CSF specimen and received at least 4 cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine (hyperCVAD) as their initial treatment. RESULTS: Eighteen (20%) were CSF+ by MFC at the baseline, and only 6 of these patients were positive by CC. In contrast, 0 of 51 patients who were negative by MFC and had CC available were positive by CC. Despite the receipt of significantly more intra-CSF chemotherapy (P < .001), the cumulative incidence of CNS relapse by MFC was 22% among CSF+ patients versus 5% among those who were CSF- (P = .044). No such association was observed between CNS relapse and CC results (P = .42). None of the 74 CSF- patients became CSF+ during their initial treatment despite being tested a median of 5 times (range, 2-10). CSF positivity by MFC was the factor most strongly associated with CNS relapse in a series of univariate Cox models (hazard ratio, 3.7; P = .067). The initial CSF status by MFC had no significant impact on overall or event-free survival. CONCLUSIONS: MFC of CSF is superior to CC of CSF in identifying adults at high risk for CNS relapse after treatment with hyperCVAD. Surveillance of CSF by MFC has limited utility.

Survival of patients with newly diagnosed high-grade myeloid neoplasms who do not meet standard trial eligibility.

Few patients with cancer, including those with acute myeloid leukemia and high-grade myeloid neoplasms, participate in clinical trials. Broadening standard eligibility criteria may increase clinical trial participation. In this retrospective single-center analysis, we identified 442 consecutive newly diagnosed patients from 2014 to 2016. Patients were considered eligible if they had performance status 0-2, normal renal and hepatic function, no recent solid tumor, left ventricular ejection fraction (EF) ≥ 50%, and no history of congestive heart failure (CHF) or myocardial infarction (MI); ineligible patients failed to meet one or more of these criteria. We included 372 patients who received chemotherapy. Ineligible patients represented 40% of the population and had a 1-79-fold greater risk of death (95% CI 1.37, 2.33) than eligible patients. Very few patients had cardiac co-morbidities, including 2% with low EF, 4% with prior CHF, and 5% with prior MI. In multivariable analysis, ineligibility was associated with decreased survival [HR 1-44 (95% CI 1-07, 1-93)]. Allogeneic transplantation, performed in 150 patients (40%), was associated with improved survival [HR 0-66, 95% CI (0-48, 0-91)]. Therefore, standard eligibility characteristics identify a patient population with improved survival. Further treatment options are needed for patients considered ineligible for clinical trials.

Financial Implications of Early Hospital Discharge After AML-Like Induction Chemotherapy: A 4-Year Retrospective Analysis.

BACKGROUND: Early hospital discharge (EHD) after intensive acute myeloid leukemia (AML) induction chemotherapy has become routine at the University of Washington/Seattle Cancer Care Alliance over the past several years. We assessed the financial implications of EHD over the first 4 years after its broad adoption for patients with AML and other high-grade myeloid neoplasms undergoing AML-like induction chemotherapy. PATIENTS AND METHODS: We retrospectively compared charges between 189 patients with EHD who received all postinduction inpatient/outpatient care within our care system between August 2014 and July 2018 and 139 medically matched control patients who remained hospitalized for logistical reasons. Charges from the day of initial discharge (patients with EHD) or end of chemotherapy (control patients) until blood count recovery, additional chemotherapy or care transition, hospital discharge (for control patients only), an elapse of 42 days, or death were extracted from financial databases and separated into categories: facility/provider, emergency department, transfusions, laboratory, imaging, pharmacy, and miscellaneous. RESULTS: Combined charges averaged $4,157/day (range, $905-$13,119/day) for patients with EHD versus $9,248/day (range, $4,363-$48,522/day) for control patients (P<.001). The EHD cohort had lower mean facility/provider, transfusion, laboratory, and pharmacy charges but not imaging or miscellaneous charges. During readmissions, there was no statistically significant difference in daily inpatient charges between the EHD and control cohorts. After multivariable adjustment, average charges were $3,837/day lower for patients with EHD (P<.001). CONCLUSIONS: Together with previous data from our center showing that EHD is safe and associated with reduced healthcare resource utilization, this study further supports this care approach for AML and other high-grade myeloid neoplasms if infrastructure is available to enable close outpatient follow-up.

Impact of clinical, cytogenetic, and molecular profiles on long-term survival after transplantation in patients with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a heterogeneous group of clonal hematopoietic malignancies with variable clinical and molecular features. We analyzed long-term results of allogeneic hematopoietic cell transplantation in patients with CMML and determined clinical and molecular risk factors associated with outcomes. Data from 129 patients, aged 7-74 (median 55) years, at various stages of the disease and transplanted from related or unrelated donors were analyzed. Using a panel of 75 genes somatic mutations present before hematopoietic cell transplantation were identified In 52 patients. The progression-free survival rate at 10 years was 29%. The major cause of death was relapse (32%), which was significantly associated with adverse cytogenetics (hazard ratio, 3.77; P=0.0002), CMML Prognostic Scoring System (hazard ratio, 14.3, P=0.01), and MD Anderson prognostic scores (hazard ratio, 9.4; P=0.005). Mortality was associated with high-risk cytogenetics (hazard ratio, 1.88; P=0.01) and high Hematopoietic Cell Transplantation Comorbidity Index (score ≥4: hazard ratio, 1.99; P=0.01). High overall mutation burden (≥10 mutations: hazard ratio, 3.4; P=0.02), and ≥4 mutated epigenetic regulatory genes (hazard ratio 5.4; P=0.003) were linked to relapse. Unsupervised clustering of the correlation matrix revealed distinct high-risk groups with unique associations of mutations and clinical features. CMML with a high mutation burden appeared to be distinct from high-risk groups defined by complex cytogenetics. New transplant strategies must be developed to target specific disease subgroups, stratified by molecular profiling and clinical risk factors.

Outpatient induction and consolidation care strategies in acute myeloid leukemia.

PURPOSE OF REVIEW: Patients with acute myeloid leukemia (AML) are almost invariably kept in the hospital until resolution of cytopenias following intensive induction chemotherapy. This care approach is costly and may further contribute to the reduced qualify of life of these patients. This has raised interest in moving at least part of this care to the outpatient setting. Reimbursement challenges for inpatient administration of some of the new drugs approved for AML in the last 2 years adds to this interest. RECENT FINDINGS: Retrospective and smaller prospective studies have shown that outpatient management following intensive induction chemotherapy ('Early Hospital Discharge') is feasible and may be well tolerated and cost-effective. Reported experience is more limited regarding administration of intensive chemotherapy in the outpatient setting. SUMMARY: Although of interest, barriers to the successful implementation of outpatient care models, such as limited outpatient infrastructure or geographical limitations, will have to be overcome in many cancer centers. Importantly, before wide-spread introduction, the safety and 'efficacy' (e.g. reduction in medical resources and/or cost and improvement in quality of life) of outpatient care strategies will need to be further evaluated in a prospective - and ideally randomized - manner across more heterogeneous types of oncology and geographical settings.

Identification of factors predicting low-risk febrile neutropenia admissions in adults with acute myeloid leukemia (AML).

Febrile neutropenia (FN) is the most common reason for hospital readmission following chemotherapy for AML and is a major driver of healthcare resource utilization. While FN risk models exist, these have largely been developed and validated in solid tumors. We therefore examined whether baseline characteristics could predict which AML patients with FN have a lower risk of progression to severe illness. We identified adults with high-grade myeloid neoplasm (³10% blasts in blood/marrow) who received intensive chemotherapy and were admitted for FN from 2016-2023. We collected baseline clinical and disease variables. Outcomes were: infections identified, hospital length of stay (LOS), intensive care unit (ICU) admission, and survival. A "lower-risk [LR]" outcome was defined as LOS <72hrs without ICU admission or inpatient death. Univariate and multivariable (MV) logistic regression models were used to assess covariate associations with outcomes. We identified 397 FN admissions in 248 patients (median age 61 [range: 29-77] years). The median hospital LOS was 6 (range: 1-56) days; 10% required ICU admission and 3.5% died inpatient. Only 15% of admissions were LR. Infection was identified in 59% of admissions. Physiologic parameters including heart rate, blood pressure and fever height were the best predictors of LR admission and infection. We developed MV models to predict LR admission and infection with AUCs of 0.82 and AUC 0.72, respectively. Established FN and critical illness models were not predictive of outcomes in AML, where we could not identify a lower risk group; thus an AML-specific FN risk model requires further development and validation.

Dose-Adjusted EPOCH Plus Inotuzumab Ozogamicin in Adults With Relapsed or Refractory B-Cell ALL: A Phase 1 Dose-Escalation Trial.

Importance: Options for adults with relapsed or refractory B-cell acute lymphoblastic leukemia or lymphoma (B-ALL) are limited, and new approaches are needed. Inotuzumab ozogamicin (InO) has been combined with low-intensity chemotherapy, with modest improvements over historical controls, and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) treatment is safe and active for newly diagnosed ALL. Objective: To assess the safety and clinical activity of DA-EPOCH and InO in adults with relapsed or refractory B-ALL. Design, Setting, and Participants: This single-center, single-arm, nonrandomized, phase 1 dose-escalation trial included adults with relapsed or refractory CD22+ B-ALL and was conducted between September 2019 and November 2022. At least 5% blood or marrow blasts or measurable extramedullary disease (EMD) was required for enrollment. Interventions: DA-EPOCH was given on days 1 to 5, while InO was given on day 8 and day 15 of a 28-day cycle. Three dose levels were studied using a bayesian optimal interval design. Main Outcomes and Measures: The primary outcome was the maximum tolerated dose of InO when combined with DA-EPOCH, defined as the highest dose level that produced a rate of dose-limiting toxicity below 33%. Secondary objectives included response rates, survival estimates, and descriptions of toxic effects. Results: A total of 24 participants were screened and enrolled (median age, 46 [range, 28-76] years; 15 [62%] male). The median number of lines of prior therapy was 3 (range, 1-12). Three of 11 participants (27%) treated at the highest dose level (InO, 0.6 mg/m2, on day 8 and day 15) experienced dose-limiting toxicity, making this the maximum tolerated dose. No deaths occurred during the study, and only 1 patient (4%; 95% CI, 0.1%-21%) developed sinusoidal obstructive syndrome after poststudy allograft. The morphologic complete response rate was 84% (95% CI, 60%-97%), 88% (95% CI, 62%-98%) of which was measurable residual disease negative by flow cytometry. Five of 6 participants with EMD experienced treatment response. The overall response rate was 83% (95% CI, 63%-95%). Median overall survival, duration of response, and event-free survival were 17.0 (95% CI, 8.4-not reached), 15.0 (95% CI, 6.7-not reached), and 9.6 (95% CI, 4.5-not reached) months, respectively. Conclusions: In this study, adding InO to DA-EPOCH in adults with relapsed or refractory B-ALL was feasible, with high response rates and sinusoidal obstructive syndrome occurring rarely in a heavily pretreated population. Many patients were able to proceed to poststudy consolidative allogeneic hematopoietic cell transplant and/or chimeric antigen receptor T-cell therapy. Further investigation of this combination is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03991884.

Intensive Reinduction Chemotherapy Followed by Early Allogeneic Hematopoietic Cell Transplantation for Relapsed/Refractory High-Grade Myeloid Neoplasms.

Outcomes for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms remain poor, with allogeneic hematopoietic cell transplantation (HCT) the sole therapy likely to result in cure. We conducted the present study to determine the feasibility of early HCT-within 60 days of beginning reinduction chemotherapy-to see whether getting patients to HCT in an expeditious manner would expand the number of patients being offered this curative option. In this proof-of-principle feasibility study, we included adults age 18 to 75 years with R/R myeloid malignancies with ≥10% blood/marrow blasts at diagnosis who were eligible for a reduced-intensity HCT. Subjects received reinduction chemotherapy with cladribine, cytarabine, mitoxantrone, and filgrastim (CLAG-M) and proceeded to HCT with reduced-intensity conditioning (fludarabine/ melphalan). We enrolled 30 subjects, all of whom received CLAG-M reinduction, although only 9 underwent HCT within 60 days (<15, the predetermined threshold for feasibility "success"), with a median time to HCT of 48 days (range, 42 to 60 days). Eleven additional subjects received HCT beyond the target 60 days (off-study), with a median time to transplantation of 83 days (range, 53 to 367 days). Barriers to early HCT included infection, physician preference, lack of an HLA-matched donor, logistical delays, and disease progression, all of which may limit the real-world uptake of such early-to-transplantation protocols.

Poor post-induction outcomes in patients with acute myeloid leukemia previously treated with hypomethylating agents.

Patients with acute myeloid leukemia (AML) who have failed hypomethylating agents (HMA) have a poor prognosis. We examined whether high intensity induction chemotherapy could abrogate negative outcomes in 270 patients with AML or other high-grade myeloid neoplasms. Prior HMA therapy was significantly associated with a lower overall survival (OS) as compared to a reference group of patients with secondary disease without prior HMA therapy (median 7.2 vs 13.1 months). In patients with prior HMA therapy, high intensity induction was associated with a non-significant trend toward longer OS (median 8.2 vs 4.8 months) and decreased rates of treatment failure (39% vs 64%). These results redemonstrate poor outcomes in patients with prior HMA and suggest possible benefit of high intensity induction that should be evaluated in future studies.

Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms.

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone ("CLAG-M") may result in higher remission rates than standard-dose cytarabine plus anthracycline ("7 + 3") but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06-2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed.

Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML.

The multikinase inhibitor sorafenib improves event-free survival (EFS) when used with 7 + 3 in adults with newly-diagnosed acute myeloid leukemia (AML), irrespective of the FLT3-mutation status. Here, we evaluated adding sorafenib to cladribine, high-dose cytarabine, granulocyte colony-stimulating factor, and mitoxantrone (CLAG-M) in a phase 1/2 trial of 81 adults aged ≤60 years with newly diagnosed AML. Forty-six patients were treated in phase 1 with escalating doses of sorafenib and mitoxantrone. No maximum tolerated dose was reached, and a regimen including mitoxantrone 18 mg/m2 per day and sorafenib 400 mg twice daily was declared the recommended phase 2 dose (RP2D). Among 41 patients treated at RP2D, a measurable residual disease-negative complete remission (MRD- CR) rate of 83% was obtained. Four-week mortality was 2%. One-year overall survival (OS) and EFS were 80% and 76%, without differences in MRD- CR rates, OS, or EFS between patients with or without FLT3-mutated disease. Comparing outcomes using CLAG-M/sorafenib with those of a matched cohort of 76 patients treated with CLAG-M alone, multivariable-adjusted survival estimates were improved for 41 patients receiving CLAG-M/sorafenib at RP2D (OS: hazard ratio,0.24 [95% confidence interval, 0.07-0.82]; P = .023; EFS: hazard ratio, 0.16 [95% confidence interval, 0.05-0.53]; P = .003). Benefit was limited to patients with intermediate-risk disease (univariate analysis: P = .01 for OS; P = .02 for EFS). These data suggest that CLAG-M/sorafenib is safe and improves OS and EFS relative to CLAG-M alone, with benefits primarily in patients with intermediate-risk disease. The trial was registered at www.clinicaltrials.gov as #NCT02728050.

Phase II study of dose-adjusted EPOCH as initial therapy for adults with high-risk acute lymphoblastic leukemia.

Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH). Imatinib or dasatinib was added for Ph + disease; rituximab was added when CD20+. Fifty-three patients were evaluable: 28 with Ph + disease, and 25 with Ph-. All patients had ≥1 high-risk clinical feature. Measurable residual disease-negativity by multiparameter flow cytometry within 4 cycles was achieved in 71% in patients with Ph + ALL and 64% in Ph - ALL. Median overall survival (OS) was 49 months, with a 2-year OS of 71%. Median relapse-free survival (RFS) in the 47 patients that attained morphologic remission was 24 months, with a 2-year RFS of 57%. Early mortality was 2%. In summary, DA-EPOCH yields deep and durable remissions in adults with ALL comparable to some resource-intense strategies but with a low rate of treatment-related death.

Comparative analysis of infectious complications with outpatient vs. inpatient care for adults with high-risk myeloid neoplasm receiving intensive induction chemotherapy.

We recently reported an early hospital discharge (EHD) care strategy following intensive acute myeloid leukemia (AML)-like chemotherapy is safe. To evaluate its impact on infectious outcomes, we compared all adults treated from 8/1/2014 to 7/31/2018 discharging within 72 h of completing chemotherapy (EHD) with hospitalized patients (controls) across 354 induction and 259 post-remission cycles. While overall outcomes were similar, gram-positive bacteremias were more common in EHD patients than control (p<.001), although they received fewer days of IV antimicrobials (p< .001). Notably, cumulative infection risks in EHD patients were similar after induction and post-remission therapy. In multivariable analysis, only EHD status was independently associated with risk for gram-positive bacteremia (p= .01), whereas the only independent risk factor for fungal infection was fluconazole (vs. posaconazole) use (p< .001). The observation of increased rates of gram-positive bacteremias with EHD identifies improvements in catheter management as one area to further increase the safety of this care approach.

Phase 1/2 Trial of CLAG-M with Dose-Escalated Mitoxantrone in Combination with Fractionated-Dose Gemtuzumab Ozogamicin for Newly Diagnosed Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms.

Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Sixty-six patients with a median age of 65 (range: 19-80) years were enrolled. Cohorts of six and twelve patients were treated in phase 1 with one dose of GO or three doses of GO (GO3) at 3 mg/m2 per dose. Since a maximum-tolerated dose was not reached, the recommended phase 2 dose (RP2D) was declared to be GO3. At RP2D, 52/60 (87%) patients achieved a complete remission (CR)/CR with incomplete hematologic recovery (CRi), 45/52 (87%) without flow cytometric measurable residual disease (MRD). Eight-week mortality was 0%. Six- and twelve-month event-free survival (EFS) were 73% and 58%; among favorable-risk patients, these estimates were 100% and 95%. Compared to 186 medically matched adults treated with CLAG-M alone, CLAG-M/GO3 was associated with better survival in patients with favorable-risk disease (EFS: p = 0.007; OS: p = 0.030). These data indicate that CLAG-M/GO3 is safe and leads to superior outcomes than CLAG-M alone in favorable-risk AML/high-grade myeloid neoplasm.

Practice patterns and outcomes for adults with acute myeloid leukemia receiving care in community vs academic settings.

Consistent with observations in other disease settings, retrospective studies have indicated that treatment outcomes for adults with acute myeloid leukemia (AML) are better in higher- vs lower-volume hospitals and academic vs nonacademic centers, with greatest benefits noted in acute promyelocytic leukemia. Younger age, more frequent receipt of chemotherapy and hematopoietic cell transplantation, and differences in comorbidities and socioeconomic factors may partially account for these differences. With new therapeutic options including oral small molecule inhibitors and parenteral drugs suitable for outpatient administration, there is increasing interest from patients and physicians in treating AML in the community setting and avoiding referral to academic centers. This may be particularly true for older adults, for whom treatment rates in the community have historically been low, and for those with comorbidities, because treatment benefits are estimated to be low, and thus travel to academic centers is perceived as especially burdensome. How the volume-outcome relationship is affected by the shift of the treatment landscape in AML over the last few years is unknown. Additionally, improvements in supportive care (transfusion support, broad-spectrum oral antimicrobials), resulting in gradually decreasing early death rates over time, and the growing focus on the impact of AML therapy on quality of life and treatment cost concerns further fuel the larger trend toward an increasing proportion of care delivered in the outpatient setting. Here, we examine whether the current shift of administering chemotherapy and supportive care to the outpatient setting can be translated to the community setting without compromising patient outcomes.