Improved tolerability by a modified intermittent treatment schedule of dasatinib for patients with chronic myeloid leukemia resistant or intolerant to imatinib

Intermittent dosing of dasatinib with a once daily regimen has been shown to reduce side effects while preserving clinical efficacy in early and advanced phase chronic myeloid leukemia (CML). Yet, hematologic toxicity and fluid retention demand a dose modification or treatment discontinuation in selected patients. Patients resistant or intolerant to imatinib were retrospectively evaluated based on the toxicity-guided administration of a dose-reduced dasatinib regimen. Patients were treated with an on/off regimen (3 to 5 days on, 2 to 4 days off) to allow regression of dasatinib-dependent off-target toxicity. Patients were followed up by routine hematologic and cytogenetic assessment and molecular monitoring to safeguard clinical response to the altered drug schedule. Thirty-three CML patients primarily in chronic phase with imatinib intolerance (n?=?11) or resistance (n?=?22) were investigated. Nonexclusive reasons for dose reduction were hematologic toxicity (17/33, 51 %) and pleural effusions (18/33, 55 %). On/off treatment with a weekend drug holiday significantly reduced pleural effusions and hematologic toxicity. Eighteen of 31 (58 %) patients showed effective disease control despite reduced total weekly dasatinib doses, either demonstrated by achieving an improved response level (12/31) or keeping the response level achieved by conventional continuous dosing (6/31). Of note, 10/12 patients with subsequently improved response have been treated for a minimum of 6 months with continuous dosing dasatinib regimens without having achieved the response level achieved after allowing drug holiday. Weekend treatment interruption of dasatinib allows continuation of dasatinib treatment for patients suffering from side effects. These data mandate prospective investigation of alternative intermittent targeting regimens.     

Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival

Background

The antifolate agent methotrexate is an important component of maintenance therapy in acute lymphoblastic leukemia, although methotrexate-related toxicity is often a reason for interruption of chemotherapy. Prediction of toxicity is difficult because of inter-individual variability susceptibility to antileukemic agents. Methotrexate interferes with folate metabolism leading to depletion of reduced folates.

Design and Methods

The aim of this study was to investigate the influence of polymorphisms for folate metabolizing enzymes with respect to toxicity and survival in adult patients with acute lymphoblastic leukemia treated with methotrexate maintenance therapy. To this purpose, we evaluated possible associations between genotype and hematologic and non-hematologic toxicity and effects on survival at 2 years of follow-up in patients with acute lymphoblastic leukemia.

Results

Polymorphisms in the genes encoding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and in dihydrofolate reductase (DHFR 19 bp deletion) significantly increased the risk of hepatotoxicity in single (odds ratio 5.23, 95% confidence interval 1.13–21.95 and odds ratio 4.57, 95% confidence interval 1.01–20.77, respectively) and in combined analysis (odds ratio 6.82, 95% confidence interval 1.38–33.59). MTHFR 677C>T also increased the risk of leukopenia and gastrointestinal toxicity, whilst thymidylate synthase 28 bp repeat polymorphism increased the risk of anemia (odds ratio 8.48, 95% confidence interval 2.00–36.09). Finally, patients with MTHFR 677TT had a decreased overall survival rate (hazard ratio 2.37, 95% confidence interval 1.46–8.45).

Conclusions

Genotyping of folate polymorphisms might be useful in adult acute lymphoblastic leukemia to optimize methotrexate therapy, reducing the associated toxicity with possible effects on survival.     

Assessment of the charlson comorbidity index score,CHADS2 and CHA2DS2-VASc scores in predicting death in patients with thoracic empyema

Background

Patients with thoracic empyema have an increased risk of mortality, but their absolute rate of mortality depends on age and comorbidities.

住院共病老年人衰弱状态分布及其影响因素

目的明确住院共病老年人衰弱状态分布特点,进一步探讨其影响因素。方法横断面调查选取2015年11月至2017年7月成都市第五人民医院老年科收治的≥60岁住院共病患者440例。根据衰弱状态将患者分为衰弱组150例及非衰弱组290例,比较2组患者一般人口学资料、共病、衰弱状态及老年综合征情况。采用SPSS 23.0进行统计分析。根据数据类型,组间比较采用独立样本t检验、Mann-Whitney U检验或χ~2检验。采用Mantel-Haenszel χ~2检验分析衰弱分布趋势。危险因素分析采用向后逐步法二元logistic回归。结果 440例患者总体存在5(4,7)种慢性疾病,Charlson合并症指数(CCI)为(5.59±1.82)分。入选患者衰弱患病率为34.1%(150/440),衰弱前期占60.0%(264/440)。趋势性检验结果显示,随年龄和CCI评分升高,衰弱患病率显著增加,差异有统计学意义(P0.05);衰弱五要素中,体质量下降发生率随年龄和CCI评分增加而增加,握力下降和疲乏发生率随年龄增加而增加,差异亦有统计学意义(P0.05)。与非衰弱患者比较,衰弱组患者年龄增大,学历较低,合并慢性心力衰竭、慢性阻塞性肺疾病、抑郁、认知功能障碍、尿失禁、高跌倒风险、功能依赖的比例显著升高,但多重用药比例显著降低,差异有统计学意义(P0.05)。经校正混杂因素后,二元logistic回归分析表明,抑郁(OR=2.178,95%CI 1.252～3.790)和功能依赖(OR=1.942,95%CI 1.029～3.668)是衰弱的独立危险因素。结论住院共病老人中普遍存在衰弱,且衰弱的患病率与年龄和共病严重程度呈趋势性增加,抑郁和功能依赖与衰弱状态密切相关。     

Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily

Dasatinib is considered an effective drug in imatinib-resistant chronic myeloid leukemia. Although reported to be well-tolerated, severe events such as pleural or pericardial effusion have been reported at 140 mg daily. We examined our chronic myeloid leukemia patients treated with dasatinib at 100 mg or 50 mg daily and identified 4 of 13 patients who developed marked effusion formation. In 2 patients, grade III/IV pleural and/or pericardial effusions were recorded. All 4 patients had received previous anti-leukemia therapy but none had pre-existing cardiac or pulmonary diseases. In 3 patients, dasatinib had to be discontinued despite treatment with diuretics and glucocorticosteroids. In conclusion, dasatinib-treated chronic myeloid leukemia patients are at risk for the development of pleural and pericardial effusions even when the drug is administered at 100 mg or 50 mg daily. Therefore, all patients should be examined for pre-existing comorbidity and risk factors before starting dasatinib and all should have repeated chest X-rays during long-term dasatinib therapy.     

Colorectal cancer screening, comorbidity, and follow-up in elderly patients

OBJECTIVE: We examined the relationship between comorbid disease and performance of complete colon examination by colonoscopy or double contrast barium enema (DCBE) after positive screening fecal occult blood test (FOBT) in patients 70 years of age or older. BACKGROUND: FOBT is an accepted form of colorectal cancer (CRC) screening. Factors that influence follow-up of positive FOBT have been largely unknown. METHODS: Patients aged 70 years and older with positive FOBT between March 1, 2000 and Feb 28, 2001 were included in this retrospective medical record review performed at a single center. Comorbidity was measured by the Charlson Comorbidity Scale. RESULTS:: In our sample of 266 subjects, 193 (73%) were referred for evaluation of positive FOBT and 109 (41%) underwent a colonoscopy or DCBE within 12 months. Using the Charlson score for comorbidity, 27% of our sample scored 0, 24% scored 1, and 23% scored 2 while 26% had a Charlson score of 3 or higher. There was no association between Charlson score (0, 1, 2, and > or =3) and referral for evaluation (chi test, P = 0.28) or performance of a complete colon examination (chi test, P = 0.38). CONCLUSIONS: In this sample, only 41% of patients with positive FOBT underwent a full colon examination within 12 months of a positive FOBT. Although comorbidity burden was considerable, there was no association between comorbidity score and referral for or performance of a full colon examination. These results suggest that inappropriate patients receive CRC screening, which may contribute to delays for screening appropriate patients and diagnostic delays for others with positive screening test findings.     

Comorbidity is an independent prognostic factor in patients with advanced‐stage diffuse large B‐cell lymphoma treated with R‐CHOP: a population‐based cohort study

An observational population‐based cohort study was performed to investigate the role of comorbidity on outcome and treatment‐related toxicity in patients with newly diagnosed advanced‐stage diffuse large B‐cell lymphoma (DLBCL) treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty‐five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R‐CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R‐CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities.     

The use of Jackson-Pratt silicone flat drains as prolonged pleural catheters for the management of pleural effusions

Introduction

Imbalance between secretion and absorbtion of pleural fluid results in pleural effusion. Emergence of pleural effusion ipsilateral or contralateral to the side drained previously is named recurrent effusion. There is currently no standart approach for the management of recurrent pleural effusions.

Materials and methods

Eighteen patients, treated between 2011 and 2012 for recurrent pleural effusions due to various etiologies, not considered for surgical or other treatments, and underwent placement of prolonged pleural catheters (Jackson-Pratt drain) were included in this study. Twenty two prolonged pleural catheters were inserted in 18 patients. There were 10 females and 8 males, with mean age 59 (35-77). In 20 patients the catheters were inserted by an anterior approach, and by a posterior approach in one patient. Daily drainage above 1,500 mL was not permitted in order to avoid pulmonary edema. Catheters were removed in patients who had lung expansion and drainage under 50 mL/day.

Results

The most common etiology for pleural effusions was extrathoracic malignancy in 9 patients, primary bronchial carcinoma in 5 patients, and benign pleural effusion in 4 patients. Four patients underwent bilateral prolonged pleural catheter insertion. The catheters were retained for a mean period of 19 (10-40) days. Pleural effusion recurred two months after removal of the catheter in one patient with primary bronchial cancer (5%). Only one patient developed a complication (empyema) while under drainage (5%). Two patients died while the catheter was in place.

Conclusions

Decreased length of stay and lower costs have enabled prolonged are the major advantages of pleural catheter applications in appropriate patients compared to other treatment methods. We believe that the Jackson Pratt silicone flat drains provide effective pleurodesis along with easy application, and suggest their use as an alternative to pleurodesis in especially malignant pleural effusions and not benign pleural effusions.KEY WORDS : Pleural effusion, prolonged pleural catheter, pleurodesis     

Evaluation of four comorbidity indices and Charlson comorbidity index adjustment for colorectal cancer patients

Introduction

Cancer survival is related not only to primary malignancy but also to concomitant nonmalignant diseases. The aim of this study was to investigate the prognostic capacity of four comorbidity indices [the Charlson comorbidity index (CCI), the Elixhauser method, the National Institute on Aging (NIA) and National Cancer Institute (NCI) comorbidity index, and the Adult Comorbidity Evaluation-27 (ACE-27)] for both cancer-related and all-cause mortality among colorectal cancer patients. A modified version of the CCI adapted for colorectal cancer patients was also built.

Methods

The study population comprised 468 cases of colorectal cancer diagnosed between 1 January 2000 and 31 December 2010 at a community hospital. Data were prospectively collected and abstracted from patients’ clinical records. Kaplan-Meier method and multivariate logistic regression models were performed for survival and risk of death analysis.

Results

Only moderate or severe renal disease [hazard ratio (HR) 2.71, 95 % confidence interval (CI) 1.11–6.63] and AIDS (HR 3.27, 95 % CI 1.23–8.68) were independently associated with cancer-specific mortality, with a population attributable risk of 5.18 and 4.36 %, respectively. For each index, the highest comorbidity burden was significantly associated with poorer overall survival (NIA/NCI: HR 2.14, 95 % CI 1.14–4.01; Elixhauser: HR 1.98, 95 % CI 1.09–1.42; ACE-27: HR 1.78, 95 % CI 1.07–1.23; CCI: HR 1.68, 95 % CI 1.05–1.42) and cancer-specific survival. The modified version of the CCI resulted in a higher predictive power compared with other indices studied (cancer-specific mortality HR?=?2.37, 95 % CI 1.37–4.08).

Conclusions

The comorbidity assessment tools provided better prognostic prevision of prospective outcome of colorectal cancer patients than single comorbid conditions.     

Charlson comorbidity index and a composite of poor outcomes in COVID-19 patients: A systematic review and meta-analysis

Background and aimsThe ongoing COVID-19 pandemic is disproportionately affecting patients with comorbidities. Therefore, thorough comorbidities assessment can help establish risk stratification of patients with COVID-19, upon hospital admission. Charlson Comorbidity Index (CCI) is a validated, simple, and readily applicable method of estimating the risk of death from comorbid disease and has been widely used as a predictor of long-term prognosis and survival.MethodsWe performed a systematic review and meta-analysis of CCI score and a composite of poor outcomes through several databases.ResultsCompared to a CCI score of 0, a CCI score of 1–2 and CCI score of ≥3 was prognostically associated with mortality and associated with a composite of poor outcomes. Per point increase of CCI score also increased mortality risk by 16%. Moreover, a higher mean CCI score also significantly associated with mortality and disease severity.ConclusionCCI score should be utilized for risk stratifications of hospitalized COVID-19 patients.     

Serious events in older Ontario residents receiving bowel preparations for outpatient colonoscopy with various comorbidity profiles: a descriptive, population-based study

BACKGROUND:

Polyethylene glycol-based bowel preparations (PEGBPs) and sodium picosulfate (NaPS) are commonly used for bowel cleansing before colonoscopy. Little is known about adverse events associated with these preparations, particularly in older patients or patients with medical comorbidities.

OBJECTIVE:

To characterize the incidence of serious events following outpatient colonoscopy in patients using PEGBPs or NaPS.

METHODS:

The present population-based retrospective cohort study examined data from Ontario health care databases between April 1, 2005 and December 31, 2007, including patients ≥66 years of age who received either PEGBP or NaPS for an outpatient colonoscopy. Patients with cardiac or renal disease, long-term care residents or patients receiving concurrent diuretic therapy were identified as high risk for adverse events. The primary outcome was a serious event (SE) defined as a composite of nonelective hospitalization, emergency department visit or death within seven days of the colonoscopy.

RESULTS:

Of the 50,660 outpatients ≥66 years of age who underwent a colonoscopy, SEs were observed in 675 (2.4%) and 543 (2.4%) patients in the PEGBP and NaPS groups, respectively. Among high-risk patients (n=30,168), SEs occurred in 481 (2.8%) and 367 (2.8%) of patients receiving PEGBP and NaPS, respectively.

CONCLUSIONS:

The SE rate within seven days of outpatient colonoscopy was 24 per 1000 procedures, and among high-risk patients was 28 per 1000 procedures. The rates were similar for PEGBP and NaPS. Clinicians should be aware of the risks associated with colonoscopy in older patients with comorbidities.     

Prolonged pleural catheters in the management of pleural effusions due to breast cancer

Background

Breast cancer is the second most common etiologic cause in malignant pleural effusions (MPE). The aim of this study was to investigate the efficacy of long term pleural catheters in inducing self sclerosis in pleural effusions of breast cancer patients.

Methods

In this study, 26 patients with breast cancer relapleural effusions that occurred between January 2011 and July 2013, who were considered not to undergo any other treatments and managed with prolonged pleural catheters (Jackson-Pratt silicone flat drain), were retrospectively analyzed. Thirty pleural catheters were inserted in 26 patients. All patients were female, mean age was 52 (range, 37-66) years old. Drainage over 1,500 mL per day was not allowed in order to avoid a lung edema. The catheters were removed in patients who had restoration of lung expansion and drainage under 50 mL/day.

Results

The histologic subtypes in pleural effusions were invasive ductal carcinoma in 18 patients, ductal carcinoma in situ in 4, invasive lobular carcinoma in 2, tubular carcinoma in 1, and medullary carcinoma in 1. Three of the 26 patients underwent bilateral catheter insertion, and one patient underwent a reinsertion of the catheter into the same hemithorax due to a recurrence. The catheters were retained for a mean period of 18 days (range, 11-38 days). In one patient with invasive ductal carcinoma and paramalignant pleural effusion (PMPE) (3.8%), a recurrent pleural effusion was seen 34 days after removal of the catheter. There were no complications. One patient died while the catheter was in place.

Conclusions

Prolonged catheters for the management of pleural effusions in selected patients have become more popular than other treatment alternatives due to a shorter length of stay and lower costs. We recommend the use of Jackson Pratt (JP) silicone flat drains which in our opinion provide effective pleurodesis in addition to easy application in recurrent effusions caused by breast cancer.     

Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience

Background

Acute myeloid leukemia is a life-threatening disease associated with high mortality rates. A substantial number of patients require intensive care. This investigation analyzes risk factors predicting admission to the intensive care unit in patients with acute myeloid leukemia eligible for induction chemotherapy, the outcome of these patients, and prognostic factors predicting their survival.

Design and Methods

A total of 406 consecutive patients with de novo acute myeloid leukemia (15–89 years) were analyzed retrospectively. Markers recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive protein, and Charlson comorbidity index. In patients requiring critical care, the value of the Simplified Acute Physiology Score II, the need for mechanical ventilation, and vasopressor support were recorded at the time of intensive care unit admission. The independent prognostic relevance of the parameters was tested by multivariate analysis.

Results

Sixty-two patients (15.3%) required intensive care, primarily due to respiratory failure (50.0%) or life-threatening bleeding (22.6%). Independent risk factors predicting intensive care unit admission were lower fibrinogen concentration, the presence of an infection, and comorbidity. The survival rate was 45%, with the Simplified Acute Physiology Score II being the only independent prognostic parameter (P<0.05). Survival was inferior in intensive care patients compared to patients not admitted to an intensive care unit. However, no difference between intensive care and non-intensive care patients was found concerning continuous complete remission at 6 years or survival at 6 years in patients who survived the first 30 days after diagnosis (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05).

Conclusions

Ongoing infections, low fibrinogen and comorbidity are predictive for intensive care unit admission in acute myeloid leukemia. Although admission was a risk factor for survival, continuous complete remission and survival of patients alive at day 30 were similar in patients who were admitted or not admitted to an intensive care unit.     

Decrease in JAK2 V617F allele burden is not a prerequisite to clinical response in patients with polycythemia vera

Background

Although reduction in the JAK2^V617F allele burden (%V617F) has been suggested as a criterion for defining disease response to cytoreductive therapy in polycythemia vera, its value as a response monitor is unclear. The purpose of this study is to determine whether a reduction in %V617F in polycythemia vera is a prerequisite to achieving hematologic remission in response to cytoreductive therapy.

Design and Methods

We compared the clinical and hematologic responses to change in %V617F (molecular response) in 73 patients with polycythemia vera treated with either interferon (rIFNα-2b: 28, Peg-rIFNα-2a: 18) or non-interferon drugs (n=27), which included hydroxyurea (n=8), imatinib (n=12), dasatinib (n=5), busulfan (n=1), and radioactive phosphorus (n=1). Hematologic response evaluation employed Polycythemia Vera Study Group criteria, and molecular response evaluation, European Leukemia Net criteria.

Results

Of the 46 treated with interferon, 41 (89.1%) had a hematologic response, whereas only 7 (15.2%) had a partial molecular response. Of the 27 who received non-interferon treatments, 16 (59.3%) had a hematologic response, but only 2 (7.4%) had a molecular response. Median duration of follow up was 2.8 years. Statistical agreement between hematologic response and molecular response was poor in all treatment groups.

Conclusions

Generally, hematologic response was not accompanied by molecular response. Therefore, a quantitative change in %V617F is not required for clinical response in patients with polycythemia vera.     

A prospective multicenter observational study of decitabine treatment in Korean patients with myelodysplastic syndrome

Background

Decitabine was evaluated for its efficacy and safety in Korean patients with myelodysplastic syndrome with IPSS score of 0.5 or over.

Design and Methods

Decitabine 20 mg/m²/day was given intravenously over one hour for five consecutive days every four weeks. The primary end point was overall response rate.

Results

A total of 101 patients were analyzed. The International Prognostic Scoring System risk category was Intermediate-2/High in 47.5%. A median of 5 courses (range 1–18) were delivered. The overall response rate was 55.4% (13 complete responses, one partial response, 23 marrow complete responses, and 19 hematologic improvements). Forty-eight patients (47.5%) showed some hematologic improvement. With a median follow-up duration of 478 days (range 69–595), median overall survival was 17.7 months. Patients who showed hematologic improvement had significantly longer overall survival than those who did not (19.2 vs. 15.9 months, P=0.006 by landmark analysis at six months). The difference in overall survival was evident in the Intermediate-2/High risk group but not in the Intermediate-1 risk group. The progression-free survival and acute myeloid leukemia-free survival were 61.9% and 77.9% at one year, respectively. Among 489 assessable treatment courses, there were 97 fever episodes requiring intravenous antimicrobials.

Conclusions

Decitabine treatment was feasible and effective in Korean patients with myelodysplastic syndrome, and the overall survival was significantly longer in patients showing hematologic improvement.     

The clinical utility of pleural YKL-40 levels in diagnosing pleural effusions

Background and objective

Recent evidence suggests that YKL-40 is a relatively new biomarker of inflammation and it is involved in the pathogenesis of several pulmonary diseases. Details of serum and pleural YKL-40 in pleural effusions however, remain unknown. We aimed to assess whether serum and pleural YKL-40 is an accurate biomarker of pleural effusions.

Methods

This clinical study was prospective, observational and cross-sectional. The concentrations of serum and pleural fluid YKL-40 and conventional pleural marker levels were measured in 80 subjects with pleural effusions, including 23 transudates caused by congestive heart failure (CHF), and 57 exudates including 23 parapneumonic, 22 malignant and 12 tuberculous pleural effusions (TBPEs).

Results

Median pleural fluid YKL-40 levels were higher in exudates than in transudates (219.4 and 205.9 ng/mL, respectively, P<0.001). High pleural YKL-40 levels, with a cutoff value of >215 ng/mL, yielded a 73% sensitivity, 73% specificity, likelihood ratio 2.8 for diagnosing exudate, with an area under the curve of 0.770 [95% confidence intervals (CI): 0.657-0.884]. Pleural YKL-40/serum YKL-40 ratio >1.5 yielded a 75% sensitivity, 72% specificity and likelihood ratio 2.6 for diagnosing TBPE, with an area under the curve of 0.825 (95% CI: 0.710-0.940).

Conclusions

High concentrations of pleural YKL-40 level may help to differentiate exudate from transudate and a high pleural YKL-40/serum YKL-40 ratio may be helpful in seperating TBPE from non-tuberculous effusions.KEYWORDS : Exudate, pleural effusion, transudate, tuberculosis, YKL-40     

Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy

Background

Outcomes in chronic myeloid leukemia have improved with tyrosine kinase inhibitor treatment. However, little is known about outcomes of chronic myeloid leukemia in adolescent and young adult patients.

Design and Methods

We reviewed all 468 chronic myeloid leukemia patients treated at our institution with tyrosine kinase inhibitors as initial therapy: imatinib (n=281), nilotinib (n=98) or dasatinib (n=89).

Results

Median age was 47 years, median follow up 71 months and median treatment time with initial tyrosine kinase inhibitors 48 months. Adolescent and young adult was defined as aged 15–29 years. Sixty-one adolescent and young adult patients were identified. The only significant differences between adolescent and young adult and older patients were incidence of splenomegaly and distribution in Sokal risk groups. Only 3 adolescent and young adult patients have died. Rates of complete cytogenetic, major molecular and complete molecular response were significantly higher in older patients compared to adolescent and young adult patients, with a favorable trend in event-free survival for older patients. Transformation-free and overall survival were similar for the two groups.

Conclusions

The unfavorable trend in outcome for adolescent and young adult patients with chronic myeloid leukemia is unexpected. Additional research in this population is required to better define outcomes, understand the cause of this difference, and to help make better treatment recommendations.     

A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy

Background

The treatment of acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large, prospective studies have been performed in this setting. Given the established activity of hypomethylating agents such as 5-aza-2''-deoxycytidine (decitabine) in myelodysplastic syndromes and acute myeloid leukemia with 20–30% bone marrow blasts, we investigated whether this drug is also active in patients with more than 30% blasts.

Design and Methods

To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy, 227 patients (median age, 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome were treated with this hypomethylating agent. During the initial decitabine treatment (135 mg/m² total dose infused intravenously over 72 hours every 6 weeks), a median of two cycles was administered (range, 1–4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses (range, 1–19) with a lower dose of decitabine (20 mg/m²) infused over 1 hour on 3 consecutive days every 4–6 weeks.

Results

The complete and partial remission rate was 26%, 95% CI (20%, 32%), and an antileukemic effect was noted in 26% of patients. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes also responded. The median overall survival from the start of decitabine treatment was 5.5 months (range, 0–57.5+) and the 1-year survival rate was 28%, 95%CI (22%,34%). Toxicities were predominantly hematologic.

Conclusions

Decitabine is well tolerated by older, medically non-fit patients with acute myeloid leukemia; myelosuppression is the major toxicity. The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome. Because of these encouraging results, randomized studies evaluating single-agent decitabine versus conventional treatment are warranted. The study is registered with the German Clinical Trials Registry, number DRKS00000069.     

Availability and feasibility of structured,routine collection of comorbidity data in a colorectal cancer multi-disciplinary team (MDT) setting

Purpose

Availability of comorbidity assessment at multi-disciplinary team (MDT) discussions is cornerstone in making the MDT process more robust and decisive in optimising treatment and improving quality of survivorship. Comorbidity assessments using tools, such as the ACE-27 questionnaire would aid in optimising the decision-making process at MDTs so that treatment decisions can be made without delay. This study determined the availability of comorbidity data in a CRC MDT and the feasibility of routine comorbidity data collection using the validated ACE-27 questionnaire. Secondary aims determined the optimal time and method of collecting comorbidity data.

Methods

A retrospective mapping exercise (phase I; 6-months) examined the availability of comorbidity data within the MDT. Phase II prospectively collected comorbidity data using ACE-27 for a 3-month period following a short pilot.

Results

In phase I, 73/135 (54%) patients had comorbidity data readily available informing the MDT discussion; 62 patients lacked this information. After a review of the patient records, it was clear that 41 of these 62 also had comorbidities and 21 out of the 135 had ≥?2 major system disorders. Common referral sources to the MDT were surgical outpatient clinics (42%) and the endoscopy unit (13%). The average lead-time from referral to MDT discussion was 14 days. In phase II, an ACE-27 questionnaire was prospectively administered in 50 patients, mean age 54 years (range 20–84). Male: female ratio 26:24. Average time to administer ACE-27 was 4.8 min (range 1–15).

Conclusions

The phase I study confirmed the widely acknowledged view of poor comorbidity data availability within a CRC MDT. Phase II demonstrated the feasibility of routinely collecting comorbidity data using ACE-27.