White Blood Cell Count In Group Research Articles

Admission Total Leukocyte Count as a Predictor of Mortality in Cardiac Intensive Care Unit Patients

BackgroundInflammation is a sequela of cardiovascular critical illness and a risk factor for mortality. ObjectivesThis study aimed to evaluate the association between white blood cell count (WBC) and mortality in a broad population of patients admitted to the cardiac intensive care unit (CICU). MethodsThis retrospective cohort study included patients admitted to the Mayo Clinic CICU between 2007 and 2018. We analyzed WBC as a continuous variable and then categorized WBC as low (<4.0 × 103/mL), normal (≥4.0 to <11.0 × 103/mL), high (≥11.0 to <22.0 × 103/mL), or very high (≥22.0 × 103/mL). The association between WBC and in-hospital mortality was evaluated using multivariable logistic regression and random forest models. ResultsWe included 11,699 patients with a median age of 69.3 years (37.6% females). Median WBC was 9.6 (IQR: 7.4-12.7). Mortality was higher in the low (10.5%), high (12.0%), and very high (33.3%) WBC groups relative to the normal WBC group (5.3%). A rising WBC was incrementally associated with higher in-hospital mortality after adjustment (AICc adjusted OR: 1.03 [95% CI: 1.02-1.04] per 1 × 103 increase in WBC). After adjustment, only the high (AICc adjusted OR: 1.37 [95% CI: 1.15-1.64]) and very high (AICc adjusted OR: 1.99 [1.47-2.71]) WBC groups remained associated with increased risk of in-hospital mortality. ConclusionsLeukocytosis is associated with an increased mortality risk in a diverse cohort of CICU patients. This readily available marker of systemic inflammation may be useful for risk stratification within the increasingly complex CICU patient population.

Brucella Epididimorşiti Tanısında Hematolojik Parametrelerin Değerlendirilmesi: Brucella Epididimorşiti İle Non-Brucella Epididimorşitlerin Karşılaştırılması

Objective: To analyze the parameters that can facilitate the differential diagnosis of brucella epididymorchitis (BEO) and non-brucella epididymorchitis (NBEO) and to facilitate early diagnosis. Material And Methods: The data of 23 BEO patients and 80 NBEO patients, who applied in a tertiary center in eastern Turkey, where brucellosis is common, were retrospectively analyzed. Age, hemogram parameters (white blood cell (WBC)), neutrophil, lymphocyte, monocyte, eosinophil, basophil, platelet, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red blood cell distribution width (RDW), biochemical parameters (aspartate transaminase and alanine aminotransferase), inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and procalcitonin), urine culture, and scrotal doppler ultrasound findings were analyzed retrospectively and were compared between BEO and NBEO groups. Results: In the comparison of the BEO and NBEO groups, there was a significant difference between the two groups in WBC count, neutrophil count, monocytes count, NLR, MLR, MPV, and procalcitonin levels (p = 0.035, p = 0.007, p = 0.003, p = 0.005, p = 0.01, p &lt; 0.001, p &lt; 0.001, respectively). Conclusions: The NLR may be promising for use in the early diagnosis of BEO. The MPV also drew attention as parameters that can be evaluated

Prediction of Resistance to Hydroxyurea Therapy in Patients with Polycythemia Vera: A Machine Learning Study (PV-AIM)

Introduction: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Thromboembolic events (TEs) are a common complication in patients (pts) with PV but can be reduced by controlling hematocrit (HCT) levels (<45%) with phlebotomy and/or hydroxyurea (HU), a first-line treatment (tx) for PV. However, in some pts HU can fail due to resistance and alternative tx options are needed, such as ruxolitinib. Machine learning was utilized to analyze real-world evidence (RWE) and identify clinical and/or laboratory variables that may be predictive of developing resistance to HU (HU-RES) tx. Methods: PV-AIM (PV advanced integrated models for prevention of TEs) is an analytical, retrospective cohort study of pts with PV that utilizes data from the US Optum database. Pts were eligible for the current analysis if they had a diagnosis of PV, were ≥18 years old, had received only HU tx for 9 months (mo), had 6 mo pre-index (first HU tx) history (laboratory data and observations) and 12 mo post-index follow-up. An ensemble machine learning classification model, Random Forest (RF), was developed to predict HU-RES in the 6-9 mo window post-index, based on the 2010 European LeukemiaNet (ELN) consensus definition for HU-RES (criteria 1, 2 and 4), and evaluated by ROC-AUC (Receiver Operating Characteristic-Area Under the Curve). The 10 variables having the greatest impact on HU-RES prediction were identified using RF variable importance; those pairs of variables that showed greatest synergy (more significant association with HU-RES than expected) in predicting HU-RES were examined and a novel heatmap-based method was developed to visualize the risk landscape of each pairwise combination. Results: Of 82,960 pts with PV identified in the Optum database (median record length 8.4 years), 2,453 pts were eligible for inclusion and 1,304 of these were assigned as HU-RES (n=733) or HU non-resistant (n=571) and were used to develop the model. The composite ROC-AUC was 0.71, illustrating the model's accuracy for predicting HU-RES at 6-9 mo post-index. Of the variables analyzed, the 10 most predictive for HU-RES (in rank order of importance) were: red blood cell count (RBC), hematocrit (HCT), red cell distribution width (RDW), age at index, hemoglobin (HGB), annualized phlebotomy count (APC), absolute neutrophil count (ANC), white blood cell count (WBC), weight, and time between diagnosis and treatment. These variables had higher values in the HU-RES pts except for 'age at index', which was lower in HU-RES pts. For these 10 variables, 45 pairwise combinations were generated to examine variable interaction. The HCT-APC pairwise combination had the strongest association with HU-RES (p=1.74E-22) at thresholds HCT 44% and APC 0.7; notably, APC was a key variable for the next 5 out of 10 most significant pairwise associations (in combination with RBC, ANC, WBC, RDW, and weight, respectively; p=7.16E-17 to 4.26E-22). Some combinations were synergistic; the most significant was RDW-HGB (synergy score: 4001) [Table] with optimal thresholds for this combination of RDW 17% and HGB 15.5 g/dL (p=4.67E-15) [Figure]. Comparisons of pts in the 'high RDW’ (≥17%; n=559) and 'low RDW’ (<17%; n=745) groups saw significant differences between these groups in WBC, ANC, RBC, lymphocytes, neutrophils, and HGB (p≤2.72E-09 for all), and neutrophil lymphocyte ratio (p=2.75E-37). Notably, a 1.36-fold greater proportion of HU-RES pts were in the 'high RDW’ than the 'low RDW’ group (p=2.74E-09). Conclusions: Failure of HU tx may put pts at risk of TEs; however, this analysis has shown that common clinical and laboratory variables can be utilized to predict the likelihood of pts developing resistance to HU before starting tx. Pre-index HCT and APC were strongly associated with HU-RES and a synergistic association between RDW and HGB provided thresholds indicative of HU-RES, which potentially could be applied in the clinic. This analysis highlights the clinical value of pt history to help identify pts at risk of HU-RES and potentially empowers physicians to proactively schedule laboratory analyses pre-HU tx to identify pts at risk, and then closer, focused monitoring of at-risk pts to take timely clinical decisions for a switch to appropriate second-line therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

White Blood Cell Count (WBC) Levels Are Associated with Molecular Profiles and Are Independent Outcome Predictors in Acute Myeloid Leukemia (AML) Patients (Pts) (Alliance)

White Blood Cell Count (WBC) Levels Are Associated with Molecular Profiles and Are Independent Outcome Predictors in Acute Myeloid Leukemia (AML) Patients (Pts) (Alliance)

The Role of Serum Laboratory Biomarkers for Complicated and Uncomplicated Appendicitis in Adolescents.

To investigate if serum biomarkers could differentiate complicated and uncomplicated appendicitis in adolescents. An cross sectional study. Department of General Surgery, Faculty of Medicine, Alanya Alaaddin Keykubat University, Alanya, Turkey, between January 2016 and December 2018. Patients operated for acute appendicitis, aged between 10 and 19 years, were retrospectively evaluated. Patients were divided according to the negative appendectomy (group 1), uncomplicated appendicitis (group 2A) and complicated appendicitis (group 2B). White blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LC), neutrophil/lymphocyte ratio (NLR), mean platelet volume (MPV), red cell distributions width (RDW), C-reactive protein (CRP), and length of hospital stay (LoHS) were analysed by ROC curve, one-way and Mann-Whitney U-tests. There were 277 adolescents (group 1=30, group 2A=205 and group 2B=42). There were statistically significant differences between the groups in WBC, NEU, LYM, NLR, CRP, LoHS. The cut-off values of NLR, WBC, and NEU were 4.1, 10.6x109/L, and 8.17x109/L, respectively for uncomplicated appendicitis, and 7.32, 11.5x109/L, and 10.3x109/L, respectively for complicated appendicitis. The cut off value of CRP was 1.3 mg/dl for complicated appendicitis. Elevated WBC, NEU, CRP and NLR may be considered useful biomarkers in assisting physical examination and other diagnostic methods in distinguishing severity of acute appendicitis. Key Words: Adolescent, Appendicitis, Neutrophil-to-lymphocyte ratio, C-reactive protein, Length of hospital stay.

The elevated admission white blood cell count relates to adverse surgical outcome of acute Stanford type a aortic dissection

BackgroundThe purpose of the study was to examine the association between white blood cell count (WBCc) on admission and early outcome in patients with the acute Stanford type A aortic dissection (TAAD).MethodsFrom January 2012 to December 2018, we retrospectively evaluated a series of 331 consecutive patients underwent surgery for TAAD in Tongji Hospital. The patients were divided into 2 groups based on the WBCc, i.e. the normal WBCc group (WBCc≤11 × 109/L) and leukocytosis group (WBCc> 11 × 109/L). The perioperative data were compared between the 2 groups. The in-hospital mortality and the compositive adverse event including multi-organ dysfunction syndrome, postoperative stroke, tracheotomy, and re-exploration for stopping bleeding were set as end points. Cox regression were used to assess the potential risk factors.ResultsThe in-hospital mortality was nearly 3 time higher in the leukocytosis group than in the normal WBCc group (20.9% vs.8.1%, P = 0.001), and 15.1% overall. For the circulatory arrest, there was significant higher mortality in patients with leukocytosis than normal WBCc group (26.1%vs.8.9%, P = 0.001). After adjustment for confounding factors, the leukocytosis was found to be a strong independent predictor of in-hospital mortality (odds ratio = 3.10; 95% confidence interval 1.38 to 6.97, P = 0.006). The leukocytosis was also a risk factor of adverse events (odds ratio = 1.80; 95% confidence interval 1.07 to 3.04, P = 0.027).ConclusionsThe WBCc within 24 h of admission for TAAD is a strong and independent predictor of in-hospital mortality as well as short-term clinical events. The results of this study have important clinical implications for risk-stratifying patients with TAAD.

Right ventricular failure following left ventricular assist device implantation is associated with a preoperative pro-inflammatory response

BackgroundSystemic inflammation during implant of a durable left ventricular assist device (LVAD) may contribute to adverse outcomes. We investigated the association of the preoperative inflammatory markers with subsequent right ventricular failure (RVF).Materials and methodsProspective data was collected on 489 patients from 2003 through 2017 who underwent implantation of a durable LVAD. Uni- and multivariable correlation with leukocytosis was determined using linear and binary logistic regression. The population was also separated into low (< 10.5 K/ul, n = 362) and high (> 10.5 K/ul, n = 127) white blood cell count (WBC) groups. Mantel-Cox statistics was used to analyze survival data.ResultsPostop RVF was associated with a higher preop WBC (11.3 + 5.7 vs 8.7 + 3.1) and C-reactive protein (CRP, 5.6 + 4.4 vs 3.3 + 4.7) levels. Multivariable analysis identified an independent association between increased WBC preoperatively with increased lactate dehydrogenase (LDH, P < 0.001), heart rate (P < 0.001), CRP (P = 0.006), creatinine (P = 0.048), and INR (P = 0.049). The high WBC group was more likely to be on preoperative temporary circulatory support (17.3% vs 6.4%, P < 0.001) with a trend towards greater use of an intra-aortic balloon pump (55.9% vs 47.2%, P = 0.093). The high WBC group had poorer mid-term survival (P = 0.042).ConclusionsPostop RVF is associated with a preoperative pro-inflammatory environment. This may be secondary to the increased systemic stress of decompensated heart failure. Systemic inflammation in the decompensated heart failure may contribute to RVF after LVAD implant.

Impact of white blood cell count on myocardial salvage, infarct size, and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a magnetic resonance imaging study

We sought to determine the relationship between white blood cell count (WBCc) and infarct size assessed by cardiovascular magnetic resonance imaging (CMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). In 198 patients undergoing primary PCI for STEMI, WBCc was measured upon arrival and CMR was performed a median of 7 days after the index event. Infarct size was measured on delayed enhancement imaging and the area at risk (AAR) was quantified on T2-weighted images. Baseline characteristics were not significantly different between the high WBCc group (>11,000/mm(3), n = 91) and low WBCc group (≤11,000/mm(3), n = 107). The median infarct size was larger in the high WBCc group than in the low WBCc group [22.0% (16.7-33.9) vs. 14.7% (8.5-24.7), p < 0.01]. Compared with the low WBCc group, the high WBCc group had a greater extent of AAR and a smaller myocardial salvage index [MSI = (AAR-infarct size)/AAR × 100]. The major adverse cardiovascular events (MACE) including cardiac death, nonfatal reinfarction, and rehospitalization for congestive heart failure at 12-month occurred more frequently in the high WBCc group (12.1 vs. 0.9%, p < 0.01). In multivariate analysis, high WBCc significantly increased the risk of a large infarct (OR 3.04 95% CI 1.65-5.61, p < 0.01), a low MSI (OR 2.08, 95% CI 1.13-3.86, p = 0.02), and 1-year MACE (OR 16.0, 95% CI 1.89-134.5, p = 0.01). In patients undergoing primary PCI for STEMI, an elevated baseline WBCc is associated with less salvaged myocardium, larger infarct size and poorer clinical outcomes.

Comparison of the surgical stress between endoscopic thyroidectomy via anterior chest approach and conventional thyroidectomy

To evaluate the difference in surgical stress between gasless endoscopic thyroidectomy through anterior chest approach and conventional thyroidectomy. The patients with thyroid nodules who would undergo thyroidectomy between November 2006 and February 2008 in Department of Otorhinolaryngology Head and Neck Surgery, Second Affiliated Hospital of Sun Yat-sen University, were randomly divided into gasless endoscopic thyroidectomy group or conventional thyroidectomy group, with 25 cases and 22 cases respectively. Before and after surgery, white blood cell count (WBC), serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured to assess the surgical stress response. At 12 h, 24 h and 48 h after surgery, no significant difference was found between the two groups in WBC (t = -0.172, 1.774 and 2.039 respectively, P > 0.05), serum CRP (t = -0.927, -1.701 and -1.813, P > 0.05) and IL-6 (t = 0.098, -2.019 and -1.121, P > 0.05). The stress response of gasless endoscopic thyroidectomy is similar with that of conventional thyroidectomy.

The analysis to risk factors of affecting the long-term patency ratio of stent planted in arteriosclerosis subclavian artery

The discussion of risk factors of affecting the long-term patency ratio of stent planted in arteriosclerosis subclavian artery. To analyse the correlation between preprocedural white blood cell count, antiplatelet agents therapy, residual stenosis in the stent, the preprocedural lesion degree of subclavian artery, serum lipid, blood sugar, blood press et al, and long-term patency of stent by Logistic regression. To explore the significant difference in preprocedural white blood cell count (WBC), antiplatelet agents therapy, residual stenosis, the preprocedural lesion degree of subclavian artery, serum lipid, blood sugar, blood press and so on between non-patency group (15 patients) and patency group (139 patients). To compare the significant difference of patency ratio of stent at the end of the survey between higher WBC (> 7.08 × 10⁹/L) group (45 patients) and lower WBC (≤ 7.08 × 10⁹/L) group (109 patients) by χ²-test. Among 154 stents planted in subclavian artery, the patency ratio of 1-year was 96.1% (148/154), and that of 3-year was 88.5% (69/78). The risk factors of the descended patency ratio of stent are respectively the increasing preprocedural white blood cell count, no antiplatelet agents therapy and residual stenosis [OR 3.135 (P < 0.001, 95%CI 1.781 - 5.519); OR 5.818 (P = 0.005, 95%CI 1.688 - 20.057) and OR 5.253 (P = 0.014, 95%CI 1.391 - 19.838)]. There is the significant difference in preprocedural WBC between non-patency group and patency group (t = -5.008, P < 0.001, (8.15 ± 1.59) × 10⁹/L (5.25 × 10⁹/L - 10.75 × 10⁹/L) vs (6.01 ± 1.36) × 10⁹/L (4.07 × 10⁹/L - 8.11 × 10⁹/L). And there are the significant differences in antiplatelet agents therapy and residual stenosis between them (P = 0.002 and P = 0.025). At the end of the survey, the patency ratio of stent in subclavian artery of higher and lower WBC group is respectively 71.1% (32/45) and 98.2% (107/109) (P < 0.01). It's sustainable antiplatelet agents therapy and decreased residual stenosis the stent that key elements to improve the long-term patency ratio of stent planted in subclavian artery. In addition, pay attention to that increasing white blood cell disturbs the long-term patency ratio of stent.

The predicting value of neutrophil VCS parameters in the diagnosis of bacterial infection

Objective To investigate the clinical value of mean channel of neutrophil volume (MNV), mean channel of neutrophil conductivity (MNC) and mean channel of neutrophil scatter (MNS) in predicting acute bacterial infection.Methods Peripheral blood samples from 112 patients with positive blood cultures for bacteria,70 healthy subjects and 45 non-infectious subjects with high white blood cell count(WBC) were studied using the Coulter LH 750 hematology analyzer.MNV, MNC, MNS and neutrophil volume distribution width (NDW) were retrospectively analyzed and compared with total WBC, percentage of neutrophils,neutrophil left-shift and CRP.112 blood bacterial infections were grouped according to WBC count (A:WBC ＜11.0×109 /L;B:11.0×109/L≤WBC＜15.0×109 /L;C:WBC≥15.0×109 /L) and neutrophil rate (NE ＜ 0.85 and NE ≥ 0.85 ).Results MNV and NDW increased significantly in septic patients (154.17 ± 10.08,24.36 ± 4.14 ) compared with those of healthy control group (142.09 ± 4.13,19.04 ± 1.97) and non-infectious patients with high WBC group ( 150.63 ± 8.14,20.19 ± 4.73 ).There was statistically significant difference (F value were 20.738 and 28.190 respectively,P ＜ 0.01 ). On the contrary, MNS decreased significantly in septic patients (137.15 ± 7.61 ) compared with that of healthy group (144.51±4.36) and nonspetic patients with high WBC group (142.45±7.11) ,there was significant statistical difference (F=5.217,P＜0.01).The MNV, NDW and MNS of A group were 148.09±5.76,22.39±1.97,140.07±6.11 respectively.The MNV, NDW and MNS of B group were 152.83±5.75,24.14±1.35,141.44±5.35 respectively.The MNV, NDW and MNS of C group were 164.28±6.49,29.42±5.93,134.27±9.61 respectively. There was statistically significant difference compared with healthy group (F value were 24.720,31.642,7.931, P ＜ 0.01).The MNV, NDW and MNS in the group with NE ＜0.85 were 149.17±9.06,22.59±2.73,141.19±4.34 respectively.The MNV, NDW and MNS in the group with NE≥0.85 group were 159.03±10.23,27.64±4.51,135.62 ± 8.95 respectively.There was statistically significant difference compared with healthy group ( F value was 23.970,51.309,19.792,P＜0.01).With a cut-off of 150 for the MNV, a specificity of 90% and sensitivity of 70% were achieved.NDW was associated with neutrophil left-shift (r=0.33,P＜0.01).With a cut-off of 23 for the NDW, a specificity of 100% and a sensitivity of 72% were achieved.The sensitivity of the MNV and NDW was better than total white blood cells count (with a cut-off≥ 11.0×109 /L, the sensitivity was 57% ), percentage of neutrophils( with a cut-off≥0.85, the sensitivity was 44% ) and neutrophil shift to left ( with a cut-off ＞5%, the sensitivity was 66% ) and CRP (with a cut-off ≥10 mg/L, the sensitivity was 65% ).Conclusions The MNV and NDW of the neutrophil can reflect the morphologic change of neutrophil sensitively and specificialy in acute infection. As quantitative, objective and more sensitive parameters, MNV and NDW may have a potential role for predicting the acute bacterial infection. Key words: Bacterial infections; Neutrophils; Blood cell count

A Randomized Comparison of All Transretinoic Acid (ATRA) Followed by Chemotherapy and ATRA Plus Chemotherapy and the Role of Maintenance Therapy in Newly Diagnosed Acute Promyelocytic Leukemia

AbstractAll transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA→CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients ≤75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients ≤65 years of age and with an initial WBC count of ≤5,000/μL (n = 208) were randomized between ATRA→CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/μL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA →CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P = .0002) and close to significance in the elderly group (P = .086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA→CT group (P = .04, relative risk [RR] = .41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA→CT group (P = .1, RR = .62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P = .0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P= .02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P = .01), and there was a trend for better survival in patients who received maintenance ATRA (P = .22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

A Randomized Comparison of All Transretinoic Acid (ATRA) Followed by Chemotherapy and ATRA Plus Chemotherapy and the Role of Maintenance Therapy in Newly Diagnosed Acute Promyelocytic Leukemia

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA→CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients ≤75 years of age and with newly diagnosed APL were included. Induction treatment was stratified on white blood cell (WBC) count and age: patients ≤65 years of age and with an initial WBC count of ≤5,000/μL (n = 208) were randomized between ATRA→CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/μL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA →CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P = .0002) and close to significance in the elderly group (P = .086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA→CT group (P = .04, relative risk [RR] = .41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA→CT group (P = .1, RR = .62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P = .0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P= .02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P = .01), and there was a trend for better survival in patients who received maintenance ATRA (P = .22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

An open-label, randomized trial of the effects of macrophage versus granulocyte colony-stimulating factor on natural killer cell activity, lymphokine activated killer cell activity, interleukin-2 production, and leukocyte count in patients after chemotherapy for ovarian cancer

An open-label, randomized trial was carried out to determine the effects of human urine macrophage colony-stimulating factor (hM-CSF) and granulocyte colony-stimulating factor (G-CSF) on natural killer (NK) cell activity, lymphokine activated killer (LAK) cell activity, interleukin-2 (IL-2) production, and peripheral white blood cell (WBC) count in patients receiving chemotherapy for ovarian cancer. Twenty patients with ovarian cancer who had received chemotherapy consisting of a combination of carboplatin (280 mg/m 2 intravenously [IV], day 1) and cisplatin (70 mg/m 2 IV, day 2) were randomly divided into two groups. Group A was given hM-CSF 8 × 10 6 U/body per day IV for 5 days from the 14th day after the start of chemotherapy, and group B was given G-CSF 75 μg/body per day subcutaneously for 5 days from the 14th day after the start of chemotherapy. Blood was sampled four times as follows: before chemotherapy; before CSF administration; on the third day of CSF administration; and on the day after completion of CSF administration. The number of peripheral WBCs, NK cell activity, LAK activity, and IL-2 production were determined. The final evaluation was performed in 16 patients (8 patients in each group). In group B, the number of peripheral WBCs was significantly increased to 7763 ± 2477/mm 3 on the third day of G-CSF administration compared with the number before administration of G-CSF (4113 ± 1186/mm 3). There are no significant changes in WBC count in group A. No significant differences in NK cell activity or IL-2 production were observed between groups. In group A, NK cell activity was significantly increased to 34 ± 14% on the third day of hM-CSF administration compared with the activity before administration of hM-CSF (23 ± 15%). In group A, IL-2 production increased to 11.9 ± 6.0 U/mL on the third day of hM-CSF administration compared with 5.9 ± 3.4 U/mL before administration, but the increase in IL-2 production failed to reach statistical significance. In group B, there were no significant changes in NK cell activity or IL-2 production before or after administration of G-CSF. These results suggest that G-CSF is valuable in augmenting WBC counts lowered due to anticancer chemotherapy. The results also suggest that hM-CSF is a valuable cytokine in improving immune function, particularly NK cell activity that has been suppressed by anticancer chemotherapy.