Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph), resulting from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor (TKI) therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML (CP-CML). The selection TKI therapy should be based on the risk score, toxicity profile of TKI, patient's age, ability to tolerate therapy, and the presence of comorbid conditions. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CP-CML.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

IMPORTANCEPatients with acute myeloid leukemia (AML) receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). However, the role of specialty palliative care for improving the QOL and care for this population is currently unknown.OBJECTIVE To assess the effect of integrated palliative and oncology care (IPC) on patient-reported and EOL outcomes in patients with AML. DESIGN, SETTING, AND PARTICIPANTSWe conducted a multisite randomized clinical trial of IPC (n = 86) vs usual care (UC) (n = 74) for patients with AML undergoing intensive chemotherapy. Data were collected from January 2017 through July 2019 at 4 tertiary care academic hospitals in the United States.INTERVENTIONS Patients assigned to IPC were seen by palliative care clinicians at least twice per week during their initial and subsequent hospitalizations. MAIN OUTCOMES AND MEASURESPatients completed the 44-item Functional Assessment of Cancer Therapy-Leukemia scale (score range, 0-176) to assess QOL; the 14-item Hospital Anxiety and Depression Scale (HADS), with subscales assessing symptoms of anxiety and depression (score range, 0-21); and the PTSD Checklist-Civilian version to assess posttraumatic stress disorder (PTSD) symptoms (score range, 17-85) at baseline and weeks 2, 4, 12, and 24. The primary end point was QOL at week 2. We used analysis of covariance adjusting and mixed linear effect models to evaluate patient-reported outcomes. We used Fisher exact test to compare patient-reported discussion of EOL care preferences and receipt of chemotherapy in the last 30 days of life. RESULTSOf 235 eligible patients, 160 (68.1%) were enrolled; of the 160 participants, the median (range) age was 64.4 (19.7-80.1) years, and 64 (40.0%) were women. Compared with those receiving UC, IPC participants reported better QOL (adjusted mean score, 107.59 vs 116.45; P = .04), and lower depression (adjusted mean score, 7.20 vs 5.68; P = .02), anxiety (adjusted mean score, 5.94 vs 4.53; P = .02), and PTSD symptoms (adjusted mean score, 31.69 vs 27.79; P = .01) at week 2. Intervention effects were sustained to week 24 for QOL (β, 2.35; 95% CI, 0.02-4.68; P = .048), depression (β, −0.42; 95% CI, −0.82 to −0.02; P = .04), anxiety (β, −0.38; 95% CI, −0.75 to −0.01; P = .04), and PTSD symptoms (β, −1.43; 95% CI, −2.34 to −0.54; P = .002). Among patients who died, those receiving IPC were more likely than those receiving UC to report discussing EOL care preferences (21 of 28 [75.0%] vs 12 of 30 [40.0%]; P = .01) and less likely to receive chemotherapy near EOL (15 of 43 [34.9%] vs 27 of 41 [65.9%]; P = .01). CONCLUSIONS AND RELEVANCEIn this randomized clinical trial of patients with AML, IPC led to substantial improvements in QOL, psychological distress, and EOL care. Palliative care should be considered a new standard of care for patients with AML.

PurposeTaxanes are a cornerstone treatment in early and advanced stage breast cancer and in other common solid tumor malignancies; however, the development of chemotherapy induced peripheral neuropathy (CIPN) often necessitates dose-reduction, which may hamper the effectiveness of the drug and compromise survival outcomes especially when used in the adjuvant setting. Limited literature is available on the prevalence and severity of dose reduction due to CIPN. We sought to determine the frequency and severity of CIPN-induced dose reduction in early stage breast cancer patients who received taxane-based chemotherapy in the neoadjuvant or adjuvant settings.MethodsWe conducted a retrospective single-institution breast cancer clinic chart review of 123 newly diagnosed breast cancer patients and treated with taxane-based neoadjuvant/adjuvant chemotherapy at the University of Maryland Greenebaum Cancer Center between January 2008 and December 2011.ResultsForty-nine of 123 (40%; 95% CI: 31-49%) patients required dose reduction. Twenty-one (17%; 95% CI: 11-25%) of these patients were dose-reduced specifically due to CIPN that developed during treatment. The median relative dose intensity (received dose/planned dose) for the 21 CIPN-induced dose reduction patients was 73.4% (range, 68.0-94.0%). Patients with diabetes appeared to have a higher risk of taxane-induced dose reduction (p-value=0.01). African-American patients and those treated with paclitaxel (rather than docetaxel) experienced a higher-risk of CIPN-induced dose reduction (p-values are <0.001 and 0.001, respectively).ConclusionsThe incidence of CIPN-associated dose reduction in our patient population was 17%. African-American patients, diabetics and subjects treated with paclitaxel had a higher risk for CIPN-associated dose reduction in our study.

Purpose Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore we asked whether adding already established effective drugs such as Topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. Experimental Design The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. Results Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared to each single therapy. Conclusions Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of AML patients that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression, and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML.