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Purpose: Sclerotic chronic graft-versus-host disease (cGVHD) represents a highly morbid and refractory form of cGVHD, and novel therapies for sclerotic cGVHD are critically needed. This study aimed to determine the efficacy of ruxolitinib in patients with corticosteroid refractory sclerotic cGVHD., Patients and Methods: In a single-arm multicenter phase II trial (N = 47), adults with sclerotic cGVHD refractory to corticosteroids and ≥one additional line of systemic therapy for cGVHD received ruxolitinib for ≥six months (ClinicalTrials.gov identifier: NCT03616184). The primary end point was complete or partial response (PR) in skin and/or joint defined according to the 2014 National Institute of Health cGVHD Consensus Criteria., Results: Following the use of ruxolitinib for a median of 11 months, PR in skin and/or joints was noted in 49% (95% CI, 34 to 64) at 6 months, with 45% having joint and fascia response and 19% having skin response. The duration of skin/joint response was 77% (95% CI, 48 to 91) at 12 months. Overall cGVHD PR was noted in 47% (95% CI, 32 to 61). Improvement in Lee Symptom Scale summary and skin subscale scores was noted in 38% of patients. With a cumulative incidence of treatment failure of 20.8% (95% CI, 10.0 to 34.1), nonrelapse mortality (NRM) of 2.2% (95% CI, 0.17 to 10.3), and no recurrent malignancy, failure-free survival (FFS) was 77.1% (95% CI, 61.3 to 87.0) at 12 months. Ruxolitinib was overall well tolerated with no new safety signals., Conclusion: The use of ruxolitinib was associated with relatively high rates of skin/joint responses and overall cGVHD responses, improvement in patient-reported outcomes, low NRM, and high FFS in patients with refractory sclerotic cGVHD. Ruxolitinib offers an effective treatment option for refractory sclerotic cGVHD.

Introduction: Many older adults with acute myeloid leukemia (AML) do not receive chemotherapy because of physicians' and patients' concern for toxicities and functional decline. This highlights the critical and urgent need to generate knowledge of functional changes following new treatments., Materials and Methods: As a part of a pragmatic single-center trial, 59 older adults ≥60 years with AML completed geriatric assessment and health-related quality of life measures before treatment and at one month and three months after chemotherapy initiation. Changes in scores of various geriatric assessment measures were computed by subtracting the baseline score from the one-month and three-month scores for each patient. Established cut-offs were used to determine a clinically meaningful change (improvement or worsening). This study provides results of descriptive exploratory analyses., Results: Patients experienced significant comorbidity burden and a high prevalence of functional impairments before treatment, with 56% of patients having ≥2 comorbid conditions, 69% having abnormal cognitive function (using Montreal Cognitive Assessment), 69% having impaired objective physical function (using Short Physical Performance Battery), and 64% having a positive depression screen (Patient Health Questionnaire-9). Patients (n = 53) received treatment with predominantly low-intensity chemotherapy; six patients received intensive chemotherapy. Among those who completed some or all of the three-month evaluation (N = 43), from baseline before treatment to three months later, cognitive function improved (38.7%) or remained stable (38.7%), objective physical function improved (51.6%) or remained stable (22.6%), and depression scores improved (9.4%) or remained stable (53.1%). Global health status score and role functioning moderately improved by a score of >16., Discussion: An exploratory analysis of our phase 2 trial demonstrated improvement or stabilization of cognitive and physical function and depression score at three months in a high proportion of older survivors of AML, despite a high prevalence of frailty and significant comorbidity burden at baseline. These results demonstrate success of treatment in improving cognitive and physical function and depression score, and, if confirmed in larger studies, should encourage oncologists to offer chemotherapy to older adults with AML., Clinical Trial Registration: The study is registered in the ClinicalTrials.gov ID: NCT03226418., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Survival benefit associated with intensive over low-intensity chemotherapy in older adults with acute myeloid leukemia (AML) is controversial. Geriatric assessment and genetic risk categories correlate with survival following intensive chemotherapy in older adults with AML and can guide treatment selection., Materials and Methods: In a single-center trial, we integrated both geriatric assessment, and genetic risk categories to personalize selection of intensive versus low-intensity chemotherapy in older adults ≥60 years with AML (NCT03226418). In the present report, we demonstrate feasibility of this approach., Results: Broad eligibility criteria and co-management of patients with community oncologists allowed enrollment of 45% of all patients with AML treated at our center during the study period. The median time from enrollment to therapy initiation was two days (range 0-9). Over half of the trial patients had a score of ≥3 on hematopoietic cell transplantation comorbidity index, impairment in physical function (Short Physical Performance Battery), and Montreal Cognitive Assessment. Three fit patients received intensive chemotherapy, whereas other patients received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 3.7% (95% confidence interval [CI] 0.7-18.3%) and at 90 days was 29.6% (95% CI 15.9-48.5%). One-year overall survival was 66% (95% CI 60-87%)., Discussion: Our data demonstrate the feasibility of integrating geriatric assessment in precision oncology trials to define fitness for intensive chemotherapy. Broad eligibility criteria and academic-community collaboration can expand access to clinical trials., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.

Background: Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low-intensity therapy, to elderly patients with newly diagnosed AML., Methods: This randomized, open-label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged ≥70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1-hour intravenous infusions of decitabine 20 mg/m 2 once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1-hour infusions of decitabine 20 mg/m 2 once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (<10 × 10 9 /L and ≥10 × 10 9 /L), and bone marrow blast percentage (≥50% vs <50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1-year survival. The trial is registered at ClinicalTrials.gov (NCT01303796)., Results: Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (P = .1468). In patients with white blood cell counts <10 × 10 9 /L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; P = .145), as was the CR rate (21.5% vs 8.6%; P = .0017)., Conclusions: The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 × 10 9 /L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed., (© 2021 American Cancer Society.)

The NCCN Guidelines for Acute Lymphoblastic Leukemia (ALL) focus on the classification of ALL subtypes based on immunophenotype and cytogenetic/molecular markers; risk assessment and stratification for risk-adapted therapy; treatment strategies for Philadelphia chromosome (Ph)-positive and Ph-negative ALL for both adolescent and young adult and adult patients; and supportive care considerations. Given the complexity of ALL treatment regimens and the required supportive care measures, the NCCN ALL Panel recommends that patients be treated at a specialized cancer center with expertise in the management of ALL This portion of the Guidelines focuses on the management of Ph-positive and Ph-negative ALL in adolescents and young adults, and management in relapsed settings.

Introduction: Older adults with acute myeloid leukemia (AML) often have significant comorbidities. We hypothesized that greater comorbidity burden predicts worse 1-month mortality and overall survival (OS) in patients ≥60 years with AML., Materials and Methods: We included 50,668 patients ≥60 years diagnosed between 2004 and 2014 from the National Cancer Database; patients were divided into 3 groups with Charlson comorbidity index (CCI) 0, 1, and ≥2. Chi-square tests were used to examine the association between CCI and different variables. We used logistic regression and Cox proportional hazard models to determine predictors of 1-month mortality and OS, respectively., Results: Among the entire cohort, 65% had CCI 0, 24% had CCI 1, and 11% had CCI ≥2. Thirty-four percent did not receive chemotherapy. Patients with CCI 0 were more likely to receive chemotherapy, especially multiagent chemotherapy and undergo upfront hematopoietic cell transplantation. In multivariate analyses, 1-month mortality and OS were significantly worse with CCI 1 or ≥2, compared with CCI 0 in the entire cohort, as the subgroup of only those patients who received chemotherapy. Younger age, male gender, higher annual income, academic facility, longer travel distance, and acute promyelocytic leukemia were associated with improved OS., Conclusion: In one of the largest real-world studies of older adults with AML, we demonstrated that greater comorbidity, measured by higher CCI, independently predicted worse early mortality and OS in older patients with AML. Higher CCI was more common with increasing age and correlated with lower likelihood of receiving chemotherapy and hematopoietic cell transplantation. Whether optimal comorbidity management and supportive care may improve outcomes needs to be studied further., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Patients living farther away from academic centers may not have easy access to resources for management of acute myeloid leukemia (AML). We aimed to analyze the effect of distance traveled on overall survival (OS) of AML patients treated at an academic center., Patients and Methods: AML patients diagnosed at the University of Nebraska Medical Center were divided into 4 groups according to the shortest distance between the cancer center and patients' residence (<25, 25-50, 50-100, and > 100 miles). Chi-square test and ANOVA were used to examine the association of distance with patient characteristics. OS, defined as the time from diagnosis of AML to death from any cause, was determined by the Kaplan-Meier method. Comparison of survival curves was done by the log-rank test. Multivariable analysis using Cox regression was performed to detect the survival effect of distance from the cancer center., Results: The total number of patients was 449. Median distance was 85 miles (interquartile range, 20-180). OS at 1 year for < 25, 25-50, 50-100, and > 100 miles was 45%, 55%, 38%, and 40% respectively (P = .6). In a Cox regression analysis, distance from treatment center, as a continuous variable, was not a significant factor for death (hazard ratio, 1.001; 95% confidence interval, 1.000-1.001). Multivariable analysis showed nonsignificant trend of increased mortality for patients traveling > 100 miles to a cancer center., Conclusion: This study did not demonstrate an association between distance from an academic cancer center and OS in AML. This finding should provide some assurance to patients who live farther away from academic centers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polypharmacy, usually defined as taking ≥5 prescribed medications, increases chances of drug-drug interactions and toxicities, and may harm cancer patients who need multiple chemotherapeutic agents and supportive medications. We analyzed the effects of polypharmacy in overall survival (OS) in acute myeloid leukemia (AML). A total of 399 patients were divided into two groups: patients with polypharmacy (≥5 medications) versus without polypharmacy (<5 medications). Polypharmacy was associated with age ≥60 years, Karnofsky Performance Status of ≤80, hematopoietic cell transplant (HCT) comorbidity index of ≥5, and adverse cytogenetics. Patients with polypharmacy were less likely to receive intensity chemotherapy or HCT. One-year OS of patients with polypharmacy versus those without polypharmacy was 29 vs. 49% ( p <.001). Polypharmacy conferred worse OS in patients <60 years (37 vs. 65% at 1 year, HR 1.95, 95% CI 1.21-3.15) but not in patients ≥60 years (26 vs. 27% at 1 year, HR 1.12, 95% CI 0.81-1.57). Thus, polypharmacy has negative impact on OS in AML, particularly among patients aged <60 years.

Background: Controversy exists regarding the optimal chemotherapy regimen for older adults with acute myeloid leukemia (AML)., Patients and Methods: We analyzed data from the US National Cancer Data Base of 25,621 patients aged 60 to 79 years, with a diagnosis of AML from 2004 to 2014, who had received single-agent versus multiagent chemotherapy. A Cox proportional hazard model was used for overall survival (OS) analysis for the entire study cohort and separately for patients who had received single-agent (n = 6743) versus multiagent (n = 6743) chemotherapy, matched for age, Charlson comorbidity index, and AML subtype., Results: The use of multiagent chemotherapy was high overall (70%) but declined with factors, such as increasing age, Charlson comorbidity index, AML subtype other than good risk, academic center, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had greater 1-year OS (43% vs. 28%), especially for patients aged 60 to 69 years and those with good-risk AML or Charlson comorbidity index of 0 to 1. OS (hazard ratio, 1.32; 95% confidence interval, 1.28-1.36) remained more favorable for the multiagent chemotherapy group on multivariable analysis. This was confirmed in a matched cohort analysis., Conclusions: To the best of our knowledge, this is the largest real-world study that has demonstrated an association between factors such as age, comorbidity, and AML subtype and the use of multiagent chemotherapy. The use of multiagent chemotherapy was associated with improved OS, especially for patients aged <70 years, those with good-risk AML, and those with a low Charlson comorbidity index., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The role of obesity in prognosis of acute myeloid leukemia (AML) is debatable. Our retrospective study aimed to determine the effect of obesity on overall survival (OS) in AML., Patients and Methods: AML patients diagnosed at University of Nebraska Medical Center were divided into 3 groups according to body mass index (BMI): normal (18.5-25 kg/m 2 ) or underweight (< 18.5 kg/m 2 ); overweight (25-30 kg/m 2 ); and obese (≥ 30 kg/m 2 ). Chi-square test, Kruskal-Wallis test, and ANOVA were used to examine the association of BMI with baseline characteristics. Mann-Whitney test was used for pairwise comparisons of hematopoietic cell transplantation (HCT) comorbidity index. Bonferroni correction was used to adjust P values. OS, defined as time from diagnosis to death from any cause, was determined by the Kaplan-Meier method; comparisons of survival curves were done using log-rank test. Cox regression analysis was performed to detect the effect of BMI on OS., Results: Of 314 patients, 38% were obese, 68% received intensive chemotherapy, and 30% underwent HCT. Patient characteristics for all BMI groups were similar except greater HCT comorbidity index in obese patients. Actual body weight was used to calculate the chemotherapy dose in 92% of obese patients. The rates of receipt of HCT in normal, overweight, and obese groups were 33%, 32%, and 25%, respectively (P = .6). One-year OS values for normal/underweight, overweight, and obese groups was 42%, 45%, and 39%, respectively (P = .31). On multivariate analysis, obesity was associated with worse OS compared to normal-weight (hazard ratio = 0.6; 95% confidence interval, 0.4-0.9; P = .03) but not overweight patients., Conclusion: Obesity confers worse prognosis in AML. Differences in OS were not the result of differences in chemotherapy dose or receipt of HCT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: This study evaluated the overall survival (OS) of older patients (≥60 years) with acute myeloid leukemia based on the intensity of treatment. Methods: This single center, retrospective study included 211 patients diagnosed between 2000 and 2016, who received 10-day decitabine, low-intensity therapy or high-intensity therapy. Cox regression examined the impact of therapy on OS. Results: Younger patients were more likely to receive high-intensity therapy. Patients who received low-intensity therapy had worse OS compared with high-intensity therapy (median OS: 1.2 vs 8.5 months; p < 0.01). OS was similar with 10-day decitabine (median OS of 6.3 months) compared with either low-intensity therapy or high-intensity therapy. Conclusion: Ten-day decitabine is an effective alternative in older patients with newly diagnosed acute myeloid leukemia.

Older patients with acute myeloid leukemia (AML) frequently have significant comorbidities, geriatric syndromes, and high-risk leukemia that make them susceptible to high early mortality, chemotherapy-related toxicities, and poor long-term survival. The receipt of chemotherapy or hematopoietic cell transplantation is low, and the choices between intensive or low-intensity chemotherapy is often not clear. Geriatric and multidisciplinary interventions targeted to optimize functional status and improve management of comorbidities may enhance chemotherapy tolerance. Comprehensive geriatric assessment, and other integrated risk assessment models have been developed to predict the risk of chemotherapy-related toxicities and survival, and may guide therapy assignment. Development of low intensity but effective therapy is a major need. Deeper understanding of the molecular biology of AML has allowed several novel therapies to enter clinical trials in recent years. Continuation of successful collaboration between several stakeholders will be necessary to build upon the clinical and research improvements made thus far.

Cancer health disparities may exist based on the facility type. We aimed to determine the association between the academic status of centers and outcomes of patients with acute myeloid leukemia (AML). Using the National Cancer Data Base, we compared 1-month mortality and long-term overall survival (OS) of 60 738 patients with AML, who received first course treatment between 2003 and 2011 at academic or nonacademic centers (community cancer program, comprehensive community cancer program, and others). Multivariate analysis was done using logistic regression for one-month mortality and Cox regression with backward elimination approach for OS. Patients treated at academic centers differed from those at nonacademic centers in that they were younger with a median age of 62 versus 70 years (P < .0001), more often an ethnic minority (P < .0001), had lower education level (P = .005), lower co-morbidity score (P < .0001), a different income (P < .0001), and insurance profile (P < .0001), and more often received chemotherapy (P < .0001) and transplant (P < .0001). Receipt of care at nonacademic centers was associated with worse 1-month mortality (29% vs. 16%, P < .0001) and 5-year OS (15% vs. 25%; P < .0001). After adjusting for prognostic covariates, the 1-month mortality (odds ratio, 1.52; 95% confidence interval, CI 1.46-1.59; P < .0001) and OS were significantly worse in nonacademic centers, compared to academic centers. Our large database study suggests that the receipt of initial therapy at academic centers is associated with lower 1-month mortality and higher long-term OS. Investigation of the underlying reasons may allow reducing this disparity., (© 2017 Wiley Periodicals, Inc.)

Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. This portion of the NCCN Guidelines for AML focuses on management and provides recommendations on the workup, diagnostic evaluation, and treatment options for younger (age <60 years) and older (age ≥60 years) adult patients., (Copyright © 2017 by the National Comprehensive Cancer Network.)

The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low-intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Atypical chronic myeloid leukemia is a rare entity that presents diagnostic and therapeutic challenges. Traditionally utilized therapeutic agents such as hydroxyurea or interferon result in a median survival of approximately two years, thus warranting identification of better options. We report a 49-year-old Caucasian female, who presented with extreme leukocytosis (white blood cells of 148,300/µL) with left shift, severe anemia, and thrombocytopenia. Following a diagnosis of atypical chronic myeloid leukemia, she was started on intravenous decitabine. She subsequently developed paraneoplastic vasculitis of large arteries, which responded to high-dose glucocorticoid. Decitabine therapy resulted in an excellent hematologic response, transfusion independence, and successful transition to an allogeneic peripheral stem cell transplantation. However, the patient subsequently succumbed to the complications of acute graft-versus-host-disease. This case illustrates an association between atypical chronic myeloid leukemia and steroid-responsive paraneoplastic vasculitis and highlights the single-agent disease activity of decitabine in atypical chronic myeloid leukemia, which may be utilized as a bridging therapy to allogeneic stem cell transplantation., (© The Author(s) 2015.)

The optimal management of hematologic malignancy-associated venous thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is unclear. This is a retrospective study of 128 adult patients with hematologic malignancies who were diagnosed with VTE. The outcome of patients with significant thrombocytopenia (≤50,000/µL) was compared with those without. Forty-seven patients (36.7%) had a platelet count ≤50,000/µL during a period of time of perceived need for new or continued anticoagulation. The median nadir platelet count in those with significant thrombocytopenia was 10,000/µL (range 2,000-45,000/µL) versus 165,000/µL (50,000-429,000/µL) in those without (P < 0.001). The median duration of significant thrombocytopenia in the first group was 10 days (1-35 days). Therapy during the period of significant thrombocytopenia included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic-dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and observation (17%). Patients without thrombocytopenia were managed with the standard of care therapy. At a median follow-up of more than 2 years, the risk of clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding (6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar in patients with or without significant thrombocytopenia. In a multivariate analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21-1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not differ based on the presence of significant thrombocytopenia. Within the limits of this retrospective study, cautious use of prophylactic-dose LMWH may be safe in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J. Hematol. 91:E468-E472, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival., Patients and Methods: This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center., Results: Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04)., Conclusion: The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Understanding the mortality patterns of patients with lymphoma and myeloma, who have undergone autologous hematopoietic stem cell transplantation (ASCT) might identify improvement opportunities., Patients and Methods: The present retrospective study included patients with lymphoma and myeloma, aged ≥ 18 years, who had undergone ASCT from 1983 to 2010 at the University of Nebraska Medical Center. Of the 2284 patients, 972 had died within first 5 years after ASCT. The patients were divided into 3 cohorts according to the time of transplantation: 1983 to 1990 (cohort I), 1991 to 2000 (cohort II), and 2001 to 2010 (cohort III). Using Cox proportional hazards regression analysis, the risk of cause-specific mortality was compared across the 3 cohorts., Results: Of a total of 1215 deaths, 972 (80%) occurred within the first 5 years after ASCT. Disease relapse (73.4%), organ failure (7.8%), infection (4.7%), and secondary malignancy (4.2%) accounted for most of the deaths. The risk of death from infection (P < .0001), but not from relapse (P = .26), organ failure (P = .68), or secondary malignancy (P = .15), had declined in the more recent cohorts., Conclusion: The 5-year overall survival of patients undergoing ASCT has improved significantly owing to a decline in infectious mortality. Our results highlight that the mortality from relapse remains the most common cause of death, warranting investigation of different strategies to reduce the incidence of relapse and improve the therapy for relapse after ASCT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) comprise a heterogeneous group of myeloid disorders with a highly variable disease course that depends largely on risk factors. Risk evaluation is therefore a critical component of decision-making in the treatment of MDS. The development of newer treatments and the refinement of current treatment modalities are designed to improve patient outcomes and reduce side effects. These NCCN Guidelines Insights focus on the recent updates to the guidelines, which include the incorporation of a revised prognostic scoring system, addition of molecular abnormalities associated with MDS, and refinement of treatment options involving a discussion of cost of care., (Copyright © 2015 by the National Comprehensive Cancer Network.)

Myelodysplastic syndromes (MDS) are probably the most common hematologic malignancies in adults over the age of 60 and are a major source of morbidity and mortality among older age groups. Diagnosis and management of this chronic blood cancer has evolved significantly in recent years and there are Food and Drug Administration-approved therapies that can extend patients' life expectancy and improve quality of life. Primary care physicians (PCPs) are often involved in the process of diagnosis and follow-up of MDS patients, especially those in low-risk groups. They can therefore play an important role in improving patient care and quality of life by ensuring early referral and participating in supportive management. There is also a shortage of oncologists which increases the importance of the role of PCPs in management of MDS patients. In the face of limited resources, PCPs can improve access and quality of care in MDS patients. This article provides an overview of the common manifestations, diagnostic approaches, and therapeutic modalities of MDS for PCPs, with a focus on when to suspect MDS, when a referral is appropriate, and how to provide appropriate supportive care for patients diagnosed with MDS.

These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL.

The myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic disorders characterized by cytopenias, dysplasia in one or more myeloid lineages, and the potential for development of acute myeloid leukemia. These disorders primarily affect older adults. The NCCN Clinical Practice Guidelines in Oncology for MDS provide recommendations on the diagnostic evaluation and classification of MDS, risk evaluation according to established prognostic assessment tools (including the new revised International Prognostic Scoring System), treatment options according to risk categories, and management of related anemia.

Canine distemper is uncommon in the pet trade in the United States, in large part due to effective vaccines against Canine distemper virus (CDV). This is a report of CDV affecting 24 young dogs of multiple breeds shortly after sale by 2 pet stores in Wyoming during August-October 2010. Cases were diagnosed over 37 days. Diagnosis was established by a combination of fluorescent antibody staining, reverse transcription polymerase chain reaction, negative stain electron microscopy, and necropsy with histopathology. Viral hemagglutinin gene sequences were analyzed from 2 affected dogs and were identical (GenBank accession no. JF283477). Sequences were distinct from those in a contemporaneous unrelated case of CDV in a Wyoming dog (JF283476) that had no contact with the pet store dogs. The breeding property from which the puppies originated was quarantined by the Kansas Animal Health Department. Puppies intended for sale were tested for CDV. Canine distemper was diagnosed on site in November 2010. At that point 1,466 dogs were euthanized to eliminate dispersal of the disease through commercial channels. The investigation underscores the risks inherent in large-scale dog breeding when vaccination and biosecurity practices are suboptimal.

Acute myeloid leukemia (AML) remains the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML provide recommendations on the diagnostic evaluation and workup for AML, risk assessment based on cytogenetic and molecular features, treatment options for induction and consolidation therapies for younger and older (age ≥ 65 years) adult patients, and key supportive care considerations.

These suggested practice guidelines are based on extensive evaluation of the reviewed risk-based data and indicate useful current approaches for managing patients with MDS. Four drugs have recently been approved by the FDA for treating specific subtypes of MDS: lenalidomide for MDS patients with del(5q) cytogenetic abnormalities; azacytidine and decitabine for treating patients with higher-risk or nonresponsive MDS; and deferasirox for iron chelation of iron overloaded patients with MDS. However, because a substantial proportion of patient subsets with MDS lack effective treatment for their cytopenias or for altering disease natural history, clinical trials with these and other novel therapeutic agents along with supportive care remain the hallmark of management for this disease. The role of thrombopoietic cytokines for management of thrombocytopenia in MDS needs further evaluation. In addition, further determination of the effects of these therapeutic interventions on the patient's quality of life is important.(116,119,120,128,129) Progress toward improving management of MDS has occurred over the past few years, and more advances are anticipated using these guidelines as a framework for coordination of comparative clinical trials.

Chronic myeloid leukemia (CML) is characterized by a 9:22 translocation resulting in production of a chimeric BCR-ABL fusion protein that has constitutive tyrosine kinase activity and drives leukemic transformation. Imatinib mesylate, a selective inhibitor of BCR-ABL, has been introduced into clinical trials with favorable toxicity and impressive activity at all disease stages. In a phase III study of diagnosed chronic phase CML, imatinib mesylate was superior to interferon plus cytarabine in cytogenetic response, freedom from disease progression, and tolerability. Hematopoietic stem cell transplantation remains the only established cure for CML. Recent reports show continued improvements with survivals after matched sibling grafts greater than 80% at 3 to 5 years. Therefore, recent advances in conventional and transplant therapy have improved treatment options for newly diagnosed patients. Sensitive and specific monitoring techniques developed for CML may help further refine treatment with regard to using these and other emerging therapies.

Human herpes virus, type 8, also called Kaposi's sarcoma-associated virus, is associated with primary effusion lymphoma, an uncommon and unusual subset of acquired immunodeficiency syndrome-related lymphomas mostly confined to body cavities, which primarily affects human immunodeficiency virus-positive men. We report the case of a 40-year-old male with primary effusion lymphoma that presented initially with generalized lymphadenopathy and hepatosplenomegaly, followed by pericardial effusion and cardiac tamponade, in a previously undiagnosed human immunodeficiency virus patient. Cytomorphological studies disclosed a large-cell lymphoma with a population of cells demonstrating intermediate CD45 expression and partial coexpression of CD20 and CD23 markers, as well as universal expression of HLA-DR, CD71, CD38, and CD-30. Molecular studies showed clonal B-cell gene rearrangements and molecular evidence of human herpes virus, type 8. This case stresses the necessity, even in the absence of the 'classical clinical features,' of molecular testing for human herpes virus, type 8 in a subset of patients with high risk for human herpes virus, type 8-associated lymphomas.