Characteristics of self-triaged emergency department visits by adults with cancer.

OBJECTIVES: Adults with a new diagnosis of cancer frequently visit emergency departments (EDs) for disease- and treatment-related issues, although not exclusively. Many cancer care providers have 24/7 clinician phone triage available, but initial recorded phone messages tend to advise patients to go to the nearest ED if they are "experiencing a medical emergency." It is unclear how well patients triage themselves to the optimal site of care. STUDY DESIGN: Cross-sectional study of tumor registry records (university patients diagnosed 2008-2018 and safety-net patients diagnosed 2012-2018) identifiably linked to electronic health records and a regional health information exchange. METHODS: We geoprocessed addresses to calculate driving time distance from the patient's home to the ED. We used mixed-effects regression to predict the diagnosis code-based severity for ED visits within 6 months of diagnosis, clustering visits within patients and hospitals. RESULTS: A total of 39,498 adults made 38,944 ED visits to 67 different hospitals. Patients self-referred for 85.5% of visits and bypassed a median (IQR) of 13 (4-33) closer EDs. Visits closer to home were not significantly more clinically severe; visits were significantly less severe if the patient self-referred (adjusted odds ratio [AOR], 0.89; 95% CI, 0.81-0.97) or they were on weekends (AOR, 0.93; 95% CI, 0.87-0.99). Reanalyzing within each individual health system also showed similar findings. CONCLUSIONS: Adults with cancer infrequently use available clinician advice before visiting the ED and may use factors other than clinical severity to determine their need for emergency care. Future work should explore the challenges that patients face navigating unplanned acute care, including reasons for underusing existing resources.

COVID-19 Communication From Seven Health Care Institutions in North Texas for English- and Spanish-Speaking Cancer Patients: Mixed Method Website Study.

BACKGROUND: The COVID-19 pandemic has created an urgent need to rapidly disseminate health information, especially to those with cancer, because they face higher morbidity and mortality rates. At the same time, the pandemic's disproportionate impact on Latinx populations underscores the need for information to reach Spanish speakers. However, the equity of COVID-19 information communicated through institutions' online media to Spanish-speaking cancer patients is unknown. OBJECTIVE: We conducted a multimodal, mixed method document review study to evaluate the equity of online information about COVID-19 and cancer available to English- and Spanish-speaking populations from seven health care institutions in North Texas, where one in five adults is Spanish-speaking. Our focus was less on the "digital divide," which conveys disparities in access to computers and the internet based on the race/ethnicity, education, and income of at-risk populations; rather, our study asks the following question: to what extent is online content useful and culturally appropriate in meeting Spanish speakers' information needs? METHODS: We reviewed 50 websites (33 English and 17 Spanish) over a period of 1 week in the middle of May 2020. We sampled seven institutions' main oncology and COVID web pages, and both internal (institutional) and external (noninstitutional) linked content. We conducted several analyses for each sampled page, including (1) thematic content analysis, (2) literacy level analysis using Readability Studio software, (3) coding using the Patient Education and Materials Assessment Tool (PEMAT), and (4) descriptive analysis of video and diversity content. RESULTS: The themes most frequently addressed on English and Spanish websites differed. While "resources/FAQs" were frequently cited themes on both websites, English websites more frequently addressed "news/updates" and "cancer+COVID," and Spanish websites addressed "protection" and "COVID data." Spanish websites had on average a lower literacy level (11th grade) than English websites (13th grade), although still far above the recommended guideline of 6th to 8th grade. The PEMAT's overall average accessibility score was the same for English (n=33 pages) and Spanish pages (n=17 pages) at 82%. Among the Dallas-Fort Worth organizations, the average accessibility of Spanish pages (n=7) was slightly lower than that of English pages (n=19) (77% vs 81%), due mostly to the discrepancy in English-only videos and visual aids. Of the 50 websites, 12 (24%) had embedded videos; however, 100% of videos were in English, including one on a Spanish website. CONCLUSIONS: We identified an uneven response among the seven health care institutions for providing equitable information to Spanish-speaking Dallas-Fort Worth residents concerned about COVID and cancer. Spanish speakers lack equal access in both diversity of content about COVID-19 and access to other websites, leaving an already vulnerable cancer patient population at greater risk. We recommend several specific actions to enhance content and navigability for Spanish speakers.

Prior Frequent Emergency Department Use as a Predictor of Emergency Department Visits After a New Cancer Diagnosis.

PURPOSE: To determine whether emergency department (ED) visit history prior to cancer diagnosis is associated with ED visit volume after cancer diagnosis. METHODS: This was a retrospective cohort study of adults (≥ 18 years) with an incident cancer diagnosis (excluding nonmelanoma skin cancers or leukemia) at an academic medical center between 2008 and 2018 and a safety-net hospital between 2012 and 2016. Our primary outcome was the number of ED visits in the first 6 months after cancer diagnosis, modeled using a multivariable negative binomial regression accounting for ED visit history in the 6-12 months preceding cancer diagnosis, electronic health record proxy social determinants of health, and clinical cancer-related characteristics. RESULTS: Among 35,090 patients with cancer (49% female and 50% non-White), 57% had ≥ 1 ED visit in the 6 months immediately following cancer diagnosis and 20% had ≥ 1 ED visit in the 6-12 months prior to cancer diagnosis. The strongest predictor of postdiagnosis ED visits was frequent (≥ 4) prediagnosis ED visits (adjusted incidence rate ratio [aIRR]: 3.68; 95% CI, 3.36 to 4.02). Other covariates associated with greater postdiagnosis ED use included having 1-3 prediagnosis ED visits (aIRR: 1.32; 95% CI, 1.28 to 1.36), Hispanic (aIRR: 1.12; 95% CI, 1.07 to 1.17) and Black (aIRR: 1.21; 95% CI, 1.17 to 1.25) race, homelessness (aIRR: 1.95; 95% CI, 1.73 to 2.20), advanced-stage cancer (aIRR: 1.30; 95% CI, 1.26 to 1.35), and treatment regimens including chemotherapy (aIRR: 1.44; 95% CI, 1.40 to 1.48). CONCLUSION: The strongest independent predictor for ED use after a new cancer diagnosis was frequent ED visits before cancer diagnosis. Efforts to reduce potentially avoidable ED visits among patients with cancer should consider educational initiatives that target heavy prior ED users and offer them alternative ways to seek urgent medical care.

Patterns and Results of Triage Advice Before Emergency Department Visits Made by Patients With Cancer.

PURPOSE: Patients with cancer undergoing treatment frequently visit the emergency department (ED) for commonly anticipated complaints (eg, pain, nausea, and vomiting). Nearly all Medicare Oncology Care Model (OCM) participants prioritized ED use reduction, and the OCM requires that patients have 24-hour telephone access to a clinician, but actual reductions in ED visits have been mixed. Little is known about the use of telephone triage for acute care. METHODS: We identified adults aged 18+ years newly diagnosed with cancer, linked to ED visits from a single institution within 6 months after diagnosis, and then analyzed the telephone and secure electronic messages in the preceding 24 hours. We coded interactions to classify the reason for the call, the main ED referrer, and other attempted management. We compared the acuity of patient self-referred versus clinician-referred ED visits by modeling hospitalization and ED visit severity. RESULTS: From 2011 to 2018, 3,247 adults made 5,371 ED visits to the university hospital and self-referred to the ED 58.5% of the time. Clinicians referred to outpatient or oncology urgent care for 10.3% of calls but referred to the ED for 61.3%. Patient self-referred ED visits were likely to be hospitalized (adjusted Odds Ratio [aOR], 0.89, 95% CI, 0.64 to 1.22) and were not more severe (aOR, 0.75, 95% CI, 0.55 to 1.02) than clinician referred. CONCLUSION: Although patients self-referred for six of every 10 ED visits, self-referred visits were not more severe. When patients called for advice, clinicians regularly recommended the ED. More should be done to understand barriers that patients and clinicians experience when trying to access non-ED acute care.

A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1.3 mg/m2 bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL.

Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma.

Brentuximab vedotin (BV) significantly improved progression-free survival in a phase 3 study in patients with relapsed or refractory Hodgkin lymphoma (RR-HL) post-autologous-haematopoietic stem cell transplant (auto-HSCT); we report the impact of BV on quality of life (QOL) from this trial. The European Quality of Life five dimensions questionnaire was administered at the beginning of each cycle, end of treatment, and every 3 months during follow-up; index value scores were calculated using the time trade-off (TTO) method for UK-weighted value sets. Questionnaire adherence during the trial was 87·5% (N = 329). In an intent-to-treat analysis, compared with placebo, TTO scores in the BV arm did not exceed the minimally important difference (MID) of 0·08 except at month 15 (-0·084; 95% confidence interval, -0·143 to -0·025). On-treatment index scores were similar between arms and did not reach the MID at any time point; mixed-effect modelling showed that BV treatment effect was not significant (P = 0·2127). BV-associated peripheral neuropathy did not meaningfully impact QOL. Utility scores for patients who progressed declined compared with those who did not; TTO scores between these patients exceeded the MID beginning at month 15. In conclusion, QOL decreased modestly with BV consolidation treatment in patients with RR-HL at high risk of relapse after auto-HSCT.

US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816.

PURPOSE: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma. PATIENTS AND METHODS: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2. PET2-negative patients (Deauville score 1 to 3) received an additional four cycles of ABVD, whereas PET2-positive patients (Deauville score 4 to 5) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for six cycles. Among 336 eligible and evaluable patients, the median age was 32 years (range, 18 to 60 years), with 52% stage III, 48% stage IV, 49% International Prognostic Score 0 to 2, and 51% score 3 to 7. RESULTS: Three hundred thirty-six of the enrolled patients were evaluable. Central review of the interim PET2 scan was performed in 331 evaluable patients, with 271 (82%) PET2-negative and 60 (18%) PET2-positive. Of 60 eligible PET2-positive patients, 49 switched to eBEACOPP as planned and 11 declined. With a median follow-up of 39.7 months, the Kaplan-Meier estimate for 2-year overall survival was 98% (95% CI, 95% to 99%), and the 2-year estimate for progression-free survival (PFS) was 79% (95% CI, 74% to 83%). The 2-year estimate for PFS in the subset of patients who were PET2-positive after two cycles of ABVD was 64% (95% CI, 50% to 75%). Both nonhematologic and hematologic toxicities were greater in the eBEACOPP arm than in the continued ABVD arm. CONCLUSION: Response-adapted therapy based on interim PET imaging after two cycles of ABVD seems promising with a 2-year PFS of 64% for PET2-positive patients, which is much higher than the expected 2-year PFS of 15% to 30%.

Following aggressive B-cell lymphoma.

In this issue of Blood, Kurtz et al report the potential clinical utility of immunoglobulin high-throughput sequencing as a tool for disease monitoring and surveillance in aggressive B-cell lymphoma.

Phase 1 study of the safety, pharmacokinetics, and antitumour activity of the BCL2 inhibitor navitoclax in combination with rituximab in patients with relapsed or refractory CD20+ lymphoid malignancies.

The oral BCL2 inhibitor navitoclax has moderate single-agent efficacy in chronic lymphocytic leukaemia (CLL) and minor activity in lymphoma in Phase 1 trials. Navitoclax synergizes with rituximab in preclinical models of B-cell lymphoid cancers. We report the safety, pharmacokinetics and clinical activity of this combination. Patients received navitoclax (200-325 mg) daily and four standard weekly doses of rituximab. Twenty-nine patients were enrolled across three dose-escalation cohorts and a safety expansion cohort (250 mg/d navitoclax). The combination was well tolerated. Common toxicities were mild diarrhoea (79%) and nausea (72%). Grade 4 thrombocytopenia occurred in 17% of patients (dose limiting at 325 mg/d). CD19(+) counts were severely reduced, while CD3(+) cells (~ 20%) and serum immunoglobulin M levels (~ 33%) were also reduced during the first year. The maximum tolerated dose for navitoclax in combination was 250 mg/d. Pharmacokinetic analyses revealed no apparent interactions between the drugs. The response rate in patients with follicular lymphoma was 9/12, including five complete responses. All five patients with CLL/small lymphocytic leukaemia achieved partial responses. One of nine patients with aggressive lymphoma responded. The addition of rituximab to navitoclax 250 mg/d is safe; the combination demonstrates higher response rates for low-grade lymphoid cancers than observed for either agent alone in previous Phase 1 trials.

Mantle cell lymphoma: observation to transplantation.

Mantle cell lymphoma as a rare non-Hodgkin B-cell lymphoma can present in different clinical presentations such as an aggressive form or a more indolent picture. Treatment modality is based on multiple factors including age, presence or absence of symptoms, and comorbidities. Watchful waiting is a reasonable approach for asymptomatic patients especially in elderly. In symptomatic patients, treatment is chemo-immunotherapy followed by maintenance immunotherapy or autologous bone marrow transplant. Allogeneic bone marrow transplant has a potential benefit of cure for relapsed/refractory cases, but it has a high mortality rate. Novel treatment with agents such as ibrutinib, a Bruton tyrosine kinase inhibitor, has shown promising results in relapse/refractory cases. We extensively review the most recent data on diagnostic and therapeutic management of mantle cell lymphoma through presenting two extreme clinical scenarios.

Clinical characteristics of 95 patients with ocular adnexal and uveal lymphoma: treatment outcomes in extranodal marginal zone subtype.

BACKGROUND: Lymphoma rarely presents in the ocular adnexa but is usually extranodal marginal zone (ENMZ) lymphoma when it does. Involved-field radiotherapy (IFRT) is the standard of care for unilateral disease, but the optimal management of more extensive disease is unclear. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and outcomes of 95 patients with ocular adnexal lymphoma (OAL) or uveal lymphoma treated or diagnosed at our institution. All patients identified were included in the risk factor analysis for progression-free survival (PFS). The initial treatment-related outcomes were assessed for ENMZ OAL only (n = 62). RESULTS: With a median follow-up of 32 months, significant risk factors for PFS after initial treatment were age (hazard ratio, 1.33; 95% confidence interval, 1.02-1.74), female gender (hazard ratio, 2.04; 95% confidence interval, 1.04-4.00), and a history of lymphoma (hazard ratio, 2.31; 95% confidence interval, 1.12-4.78). In ENMZ, IFRT was associated with improved PFS (median, 5.4 years; P < .001). Progression occurred in 7 of 39 (23%), with 6 of the 7 (86%) at systemic sites. Single-agent rituximab was typically used for bilateral ocular or systemic presentations of ENMZ OAL. Progression occurred in 7 of 11 (64%), with no progression at systemic sites. All progression events in those initially treated with rituximab occurred in the ocular adnexa. CONCLUSION: The results of the present study have confirmed IFRT as the standard for unilateral ENMZ OAL. Single-agent rituximab was an effective agent for bilateral ocular or systemic ENMZ OAL, particularly for systemic control, but ocular progression should be closely monitored. Combined modality therapy should be studied further in bilateral and systemic ENMZ OAL.

Mature results of MM-011: a phase I/II trial of liposomal doxorubicin, vincristine, dexamethasone, and lenalidomide combination therapy followed by lenalidomide maintenance for relapsed/refractory multiple myeloma.

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).

Uveal lymphoma: clinical features, diagnostic studies, treatment selection, and outcomes.

OBJECTIVE: To describe the clinical features, ancillary diagnostic studies, and treatment selection in a cohort of patients with uveal lymphoma. DESIGN: Retrospective clinical review. PARTICIPANTS: A total of 22 patients (34 affected eyes) diagnosed with uveal lymphoma between 1997 and 2013. METHODS: Data were collected regarding patient characteristics, clinical features on ophthalmic examination, ancillary imaging studies, and primary treatment selection. MAIN OUTCOME MEASURES: Relapse defined as lymphoma recurrence in the initial site of presentation, the contralateral eye, or other systemic site and overall survival. RESULTS: Fifteen patients were male (68.2%). Median age at diagnosis was 68.0 years. The choroid was involved in 21 cases (95.5%), and 1 case (4.5%) was ciliochoroidal. Other ocular adnexal structures were affected in 13 patients (59.1%), including the conjunctiva in 4 (18.2%), the orbit in 7 (31.8%), and both the conjunctiva and orbit in 2 (9.1%). Bilateral disease was present in 12 patients (54.5%). The most common presenting symptom was decreased vision in 15 patients (68.2%). The median delay in diagnosis was 4.0 months. Yellow-white choroidal infiltrates were observed on fundus examination in 34 eyes (100.0%) with corresponding hypofluorescence in 100% of cases when indocyanine green angiography was performed. Infiltrates were located anterior to the arcades (67.6%), most commonly in a diffuse (32.4%) or superotemporal (32.4%) distribution. B-scan ultrasonography detected extrascleral extension in 22 patients (75.9%) with a pattern of crescentic thickening in 19 (86.4%). Extranodal marginal zone lymphoma was the predominant (76.2%) histologic subtype. External beam radiotherapy (72.7%) was most commonly chosen for primary treatment. Systemic imaging at the time of diagnosis revealed that the majority of cases (77.3%) were localized to the eye; none of the patients developed new systemic disease (median follow-up, 30.3 months). CONCLUSIONS: Uveal lymphoma has distinctive clinical features. Overlap with ocular adnexal structures is common, and ancillary imaging is essential for evaluating the full extent of ocular disease and presence of systemic involvement.

Ocular adnexal lymphoma: assessment of a tumor-node-metastasis staging system.

PURPOSE: To assess distribution, correlations, and prognostic effect of tumor (T), node (N), and metastasis (M) staging on relapse and survival. DESIGN: Retrospective clinical review. PARTICIPANTS: Sixty-three patients diagnosed with primary ocular adnexal lymphoma (OAL) between January 1986 and November 2011. METHODS: Complete ocular examination and systemic evaluation were performed. Patients were staged according to the American Joint Committee on Cancer (AJCC) seventh edition tumor-node-metastasis (TNM) clinical staging system for OAL and followed every 6 to 12 months (median follow-up, 27.9 months). MAIN OUTCOME MEASURES: Relapse defined as lymphoma recurrence in the initial site of presentation, the contralateral ocular adnexal structures, or other systemic site and overall survival. RESULTS: There were 40 men (63.5%). The median age was 65 years (range, 24-85 years). The affected site was the conjunctiva in 27 patients (42.9%), orbit in 38 patients (60.3%), and eyelid in 3 patients (4.8%). The histologic subtype was extranodal marginal zone lymphoma (EMZL) in 51 patients (81.0%). A total of 14 patients (23.3%) had T1, 42 patients (70.0%) had T2, 1 patient (1.7%) had T3, and 3 patients (5.0%) had T4 disease. A total of 48 patients (82.8%) had N0 disease, and 10 patients (17.2%) had N1-4 disease. M stage was M0 in 47 patients (81.0%) and M1 in 11 patients (19.0%). With advanced T stage, there was an increase in both N1-4 (P = 0.045) and M1 disease (P = 0.041). M1 disease was greater among patients with N1-4 disease compared with N0 stage (50.0% vs. 12.5%, P = 0.003). Overall, 18 patients (28.6%) relapsed and 6 patients (9.5%) died. In Cox analysis, relapse was not associated with T stage (hazard ratio [HR], 1.14 per 1 level increase, P = 0.71), N stage (HR, 1.47; P = 0.51 N1-4 vs. N0), or M stage (HR, 1.22; P = 0.76 M1 vs. M0). T stage was not associated with survival (HR, 0.86; P = 0.81), whereas N1-4 had marginally worse survival than N0 (HR, 5.35; P = 0.07), and M1 had worse survival than M0 (HR, 9.27; P = 0.008). CONCLUSIONS: The TNM staging system for primary OAL is useful for precise characterization of extent of local disease. Although T stage does not predict relapse or survival, N1-4 and M1 stages indicated less favorable survival. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Adult lymphoblastic lymphoma.

Adult lymphoblastic lymphoma (LBL) is an aggressive form of non-Hodgkin lymphoma occurring in predominantly adolescent and young adult men. Lymphoblastic lymphoma is rare, accounting for 1% to 2% of all non-Hodgkin lymphomas and is of T-cell phenotype in 90% of cases. Lymphoblastic lymphoma is morphologically indistinct from acute lymphoblastic leukemia (ALL). Both express their lineage-specific markers as well as terminal deoxynucleotidyl transferase. The differences are often made on clinical grounds. Lymphoblastic lymphoma is characterized by a predominantly nodal distribution of disease, often with a large mediastinal mass. Patients with less than 25% bone marrow involvement have typically been categorized as LBL rather than ALL, although this has not been applied consistently in the literature. Gene expression studies have identified differences in gene expression, with LBL expressing higher levels of genes associated with cytoskeleton, adhesion, angiogenesis, and chemotaxis than ALL. Although LBL and ALL can be distinct clinically, chemotherapy strategies are often very similar. Acute lymphoblastic leukemia regimens, which incorporate intensive multidrug induction, consolidation, delayed intensification, and maintenance, have been shown to be superior to standard lymphoma regimens. As central nervous system (CNS) relapse is common, CNS prophylaxis with high-dose chemotherapy and intrathecal therapy is also standard. The prophylactic use of CNS irradiation has declined with the introduction of chemotherapy regimens incorporating high doses of CNS-penetrating drugs such as cytarabine and methotrexate. The use of consolidative radiation to the mediastinum remains uncertain. High-dose chemotherapy followed by autologous or allogeneic transplantation as consolidation for patients in CR1 is controversial with modern intensive chemotherapy regimens, although transplantation has a proven role in the relapse setting.