Higher Median White Blood Cell Research Articles

Risks and outcomes among coronavirus disease 2019 patients admitted to Assiut University Hospital

Introduction The clinical characteristics present with coronavirus disease 2019 (COVID-19) encompasses asymptomatic to severe disease and mortality. Clinicians need to detect patients whose risk of illness progression and unfavorable outcomes is high. Aim To evaluate potential risk factors affecting the severity and outcome of coronavirus infection in patients admitted to Assiut University. Patients and methods From October 2021 to October 2022, Assiut University Hospital served as the site of this observational analytical cross-sectional single-centered study. A full medical history, examination, radiographic, and laboratory investigations were performed on patients. Results The primary risk variables for mortality of COVID-19 patients include a greater mean age (73.61 ± 10.51) (P value<0.001). Individuals with chronic kidney disease (P value=0.005), and liver cirrhosis (P value<0.001). Those unvaccinated against COVID-19 the (P value = 0.004). Laboratory findings can be used as a predictor of infection severity as higher median white blood cell count (P value=0.044), lower median lymphocytic count (P value=0.028), higher serum ferritin (P value=0.02). Radiologically, a significant higher mean computed tomography severity score percentage is noticed among died patients (16.61 ± 4.55%) (P value<0.001). Conclusion Advanced age, patients with renal or hepatic impairment, patients with lower lymphocytic counts or with higher computed tomography severity score are linked to a worse clinical course and outcome among COVID-19 patients who were admitted to Assiut University Hospital. Trial registration ClinicalTrials.gov. NCT04860232.

Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults

BackgroundWhile Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. Patients and methodsData from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. ResultsAmong 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). ConclusionA quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as “lower-risk,” they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

488. Initial laboratory markers may help distinguish between Kawasaki Disease and Multisystem Inflammatory Syndrome in Children

Abstract Background In May of 2020, the Centers for Disease Control and Prevention defined a new diagnosis, Multisystem Inflammatory Syndrome in Children (MIS-C), described as a Kawasaki-like illness and related to the SARS-CoV-2 virus. Patients with this syndrome met criteria for inflammation, along with multiple organ system involvement. Clinically distinguishing between Kawasaki Disease (KD) and MIS-C is challenging due to significant overlap between the two disease entities. Furthermore, approximately 25-50% of MIS-C cases also meet criteria for KD. Currently there is very limited data describing specific differences in laboratory markers between KD and MIS-C to guide clinicians in diagnosis and management. This study aims to assess if quantitative laboratory data markers help distinguish between KD and MIS-C. Methods We conducted a retrospective study of patients hospitalized within two network pediatric hospitals with the diagnosis of MIS-C [M35.81] or Kawasaki Disease [M30.3] between January 1, 2019 and March 31, 2021. Children with an alternate diagnosis at discharge were excluded. Demographic characteristics and laboratory data were recorded and analyzed. Results A total of 91 pediatric patients were included in the study: 40 with MIS-C and 45 with KD. Patients with MIS-C were significantly older with a median age 5.3 years, compared to 2.4 years for KD (p=0.001). Patients with KD presented with higher median white blood cell (WBC) count, absolute lymphocyte count, and platelet count compared to those with MIS-C (p< 0.001). A higher alanine aminotransferase (ALT) was also noted (p=0.01). Patients with MIS-C were noted to have higher median ferritin levels and C-reactive protein (CRP) (p< 0.001) (Table 1). Conclusion Both MIS-C and KD are autoinflammatory disease processes that have significant overlap. Identifying differences in initial laboratory values upon presentation can lead to earlier diagnosis. A normal ferritin level may indicate KD. Disclosures All Authors: No reported disclosures

Multisystem inflammatory syndrome in children and Kawasaki disease; comparison of their clinical findings and one-year follow-up—a cross-sectional study

BackgroundStudies on Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease (KD) have yielded inconsistent results and are lacking in Asian and African countries. This study aimed to compare the laboratory and clinical features, short-term outcomes, and one-year follow-ups of a large cohort of MIS-C and KD patients.MethodsData from 176 MIS-C and 56 KD patients admitted to Tehran Children's Medical Center between January 2021 and January 2022 were collected. Patients were followed up until January 2023.ResultsWhile lymphopenia and thrombocytopenia were more prevalent in MIS-C (73.2% vs. 20% in KD, p < 0.001), KD patients exhibited a higher median white blood cell count and prevalence of anemia, along with higher fibrinogen and erythrocyte sedimentation rate levels (p < 0.001, p < 0.001, p = 0.005, p < 0.001, respectively). MIS-C patients also exhibited lower ejection fraction, a greater occurrence of pericardial effusion, and a higher incidence of coronary aneurysms and ectasia, and ascites. Echocardiography after seven days of treatment showed a reduction in pathologies for both groups, but it was significant only for MIS-C. After one year, coronary artery abnormalities remained in only six cases.ConclusionsIn conclusion, this study highlights differences between MIS-C and KD, including laboratory indices as well as echocardiographic and abdominal ultrasound findings. These findings contribute valuable data on Iranian patients to the existing literature on this topic and have significant implications for accurate diagnosis and improved management of pediatric patients presenting with these conditions.

Admission eGFR predicts in-hospital mortality independently of admission glycemia and C-peptide in patients with type 2 diabetes mellitus and COVID-19

Objective Type 2 diabetes mellitus (T2DM) and impaired kidney function are associated with a higher risk of poor outcomes of coronavirus disease 2019 (COVID-19). We conducted a retrospective study in hospitalized T2DM patients with COVID-19 to assess the association between in-hospital mortality and admission values of different hematological/biochemical parameters, including estimated glomerular filtration rate (eGFR), plasma glucose and C-peptide (the latter serving as a marker of beta-cell function). Methods The study included T2DM patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were consecutively admitted to our Institution between 1 October 2020 and 1 April 2021. Results Patients (n = 74) were categorized into survivors (n = 55) and non-survivors (n = 19). Non-survivors exhibited significantly higher median white blood cell (WBC) count, D-dimer, neutrophil-to-lymphocyte ratio, high-sensitivity C-reactive protein (hsCRP), and procalcitonin levels, as well as significantly lower median serum 25-hydroxyvitamin D [25(OH)D] levels compared to survivors. Non-survivors exhibited significantly higher median admission plasma glucose (APG) values compared to survivors (210 vs. 166 mg/dL; p = .026). There was no statistically significant difference in median values of (random) plasma C-peptide between non-survivors and survivors (3.55 vs. 3.24 ng/mL; p = .906). A significantly higher percentage of patients with an eGFR < 60 mL/min/1.73 m2 was observed in the non-survivor group as compared to the survivor group (57.9% vs. 23.6%; p = .006). A multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, sex, body mass index, major comorbidities) showed a significant inverse association between admission eGFR values and risk of in-hospital mortality (OR, 0.956; 95% CI, 0.931-0.983; p = .001). We also found a significant positive association between admission WBC count and risk of in-hospital mortality (OR, 1.210; 95% CI, 1.043–1.404; p = .011). Conclusions Admission eGFR and WBC count predict in-hospital COVID-19 mortality among T2DM patients, independently of traditional risk factors, APG and random plasma C-peptide. Hospitalized patients with COVID-19 and comorbid T2DM associated with impaired kidney function at admission should be considered at high risk for adverse outcomes and death.

Characteristics and Outcomes of Radiation Therapy-Related Myeloid Neoplasms

BACKGROUND: Therapy-related myeloid neoplasms (t-MN) develop after exposure to a variety of DNA-damaging agents including chemotherapy, radiation, and immunosuppressive therapies (IST). Recently, a cohort of radiation t-MN (Rt-MN) was described (Patel et al, Blood Adv, 2022). Most common cytogenetic and genetic abnormalities were that of chromosomes 5 and 7, and ASXL1 and TET2 mutations. However, only a smaller subset (n=16) underwent next-generation sequencing (NGS) analysis and comparison of clinicopathological features and outcomes with other forms of DNA-damaging therapies was not performed. We hypothesized that Rt-MN may have different clinicopathological features and outcomes compared to t-MN after other forms of therapy. METHODS: This retrospective, multicenter study was conducted at Mayo Clinic, Rochester (USA) and South Australian Local Health Network (South Australia, Australia). Following appropriate regulatory approvals at the respective institute, we identified 373 WHO-defined t-MN patients who had cytogenetics and NGS at t-MN diagnosis. The statistical analysis for continuous and categorical variables was performed using Mann-Whitney and chi-squared tests, respectively. Overall survival (OS) was calculated from the time of t-MN diagnosis to the last follow up or death, whichever came first using Kaplan-Meier method. Uni- and multivariate analyses were performed using Cox proportional hazard model. The statistical analysis was performed using BlueSky (Chicago, IL, USA). RESULTS: Sixty-four (17.2%) patients developed Rt-MN and 124 (33.2%) following chemoradiotherapy (chemoradiation t-MN or CRt-MN). The remaining 185 (49.6%) received chemotherapy and/or IST but did not receive radiation (non-radiation t-MN or NRt-MN). 1. Clinical characteristics: Rt-MN were significantly older at the time of primary diagnoses (Table 1) and presented with a higher median white blood cell count, absolute neutrophil count, and platelets. A significantly higher proportion of Rt-MN patients had solid primary malignancy compared to CRt-MN and NRt-MN (P<.001). 2. Biological characteristics: The proportion of patients with chromosome 5 and 7 abnormalities was significantly lower in Rt-MN patients and comparable to the previously described cohort. Similarly, a significantly lower proportion of Rt-MN patients had evidence of genomic instability in the form of complex karyotype (CK; P=.018) and monosomal karyotype (MK; P=.001) compared to CRt-MN and NRt-MN. Rt-MN was enriched in mutated SRSF2 (P=0.006), TET2 (P=.009) and NPM1 (P=.005) compared to CRt-MN and NRt-MN respectively. On the other hand, Rt-MN had a significantly lower proportion of TP53mut compared to CRt-MN and NRt-MN (P=.001). 3. Outcomes after t-MN diagnosis: Although a significantly higher proportion of Rt-MN patients received best supportive care only (P=0.004), median OS from the time of t-MN diagnosis was not different between for Rt-MN, CRt-MN, and NR-tMN (12 vs. 12.3 vs. 15 months, respectively; P=0.11). After a median follow up of 47 months, 288 (77.2%) patients died. Interestingly, among Rt-MN patients, receiving FL HMA was associated with an inferior survival compared to those receiving BSC or IC (HMA 11 mo., BSC 18 mo., and IC 73 mo., P=.01). 4. Factors predicting survival of Rt-MN patients: Univariate analysis identified hemoglobin, chromosome 5 and 7 abnormalities, CK, MK, RUNX1 and TP53 mutations, and the type of first line therapy as predictors of survival (Table 2). MVA that included the above factors, age, and type of primary disease identified RUNX1 mutation (median OS 6 mo. vs. 13 mo., P=.02) and chromosome 7 abnormalities (7.8 mo. vs. 19.4 mo., P<0.001) as independent variables for OS. CONCLUSIONS: While Rt-MN less frequently harbored the traditionally high-risk features including CK, MK, and TP53 mutation, and were less likely to receive disease-modifying therapies, survival was not different from the patients who received the other forms of DNA-damaging therapies. Possible explanations of the noted discrepancy include older age at t-MN diagnosis and under-utilization of disease-modifying therapies. IC treatment of Rt-MN appears to be associated with a favorable OS. The presence of mutated RUNX1 and chromosome 7 abnormalities are independent risk factors for survival in Rt-MN patients. In summary, Rt-MN is a distinct clinical and molecular entity within the heterogeneous t-MN category. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mycoplasma pneumoniae multilocus variable-number tandem-repeat analysis genotypes are associated with inflammatory biomarker levels in children with lower respiratory tract infections.

The multilocus variable-number tandem-repeat analysis (MLVA) typing method is commonly used in Mycoplasma pneumoniae (M. pneumoniae) epidemiology. It remains unknown if clinical manifestations of lower respiratory tract infections (LRTI) in children differ between different MLVA genotypes. We aimed to determine if specific M. pneumoniae MLVA genotypes indicate the severity of LRTI in children. We performed a retrospective study of children younger than 18 years with signs of acute M. pneumoniae LRTI from January 1, 2009, to December 31, 2014. All patients who were PCR-positive for M. pneumoniae from pharyngeal swabs and had MLVA genotype successfully defined were included in the study. We compared the epidemiological and clinical data of children infected with different MLVA genotypes. In total, 429 patients (mean age 7.4 years, SD 3.4 years; 54% boys) met the study inclusion criteria. We compared the data of patients infected with the three most common MLVA types: MLVA-3,5,6,2 (86/429), MLVA-3,6,6,2 (71/429) and MLVA-4,5,7,2 (256/429). MLVA-3,5,6,2-infected patients over 5 years of age presented with a significantly higher median C-reactive protein level (34 vs 23 vs 19 mg/L, p = .008) and a higher median white blood cell count (9.4 vs 7.9 vs 8.5 × 109/L, p = .040) compared to MLVA-3,6,6,2- and MLVA-4,5,7,2-infected patients. No such difference was observed in the group of younger than 5 years. The results from our large cohort indicate that different MLVA genotypes may have different pathogenic potential and that children with MLVA-3,5,6,2 LRTI may present with higher inflammatory marker levels in comparison with other MLVA types.

Impact of a Positive Viral Polymerase Chain Reaction on Outcomes of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.

Introduction: More than 15 million adults in the USA have chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) places a high burden on the healthcare system. Many hospital admissions are due to an exacerbation, which is suspected to be from a viral cause. The purpose of this analysis was to compare the outcomes of patients with a positive and negative respiratory virus panel who were admitted to the hospital with COPD exacerbations. Methods: This retrospective cohort study was conducted in the Geisinger Healthcare System. The dataset included 2729 patient encounters between 1 January 2006 and 30 November 2017. Hospital length of stay was calculated as the discrete number of calendar days a patient was in the hospital. Patient encounters with a positive and negative respiratory virus panel were compared using Pearson’s chi-square or Fisher’s exact test for categorical variables and Student’s t-test or Wilcoxon rank-sum tests for continuous variables. Results: There were 1626 patients with a total of 2729 chronic obstructive pulmonary disease exacerbation encounters. Nineteen percent of those encounters (n = 524) had a respiratory virus panel performed during their admission. Among these encounters, 161 (30.7%) had positive results, and 363 (69.3%) had negative results. For encounters with the respiratory virus panel, the mean age was 64.5, 59.5% were female, 98.9% were white, and the mean body mass index was 26.6. Those with a negative respiratory virus panel had a higher median white blood cell count (11.1 vs. 9.9, p = 0.0076). There were no other statistically significant differences in characteristics between the two groups. Respiratory virus panel positive patients had a statistically significant longer hospital length of stay. There were no significant differences with respect to being on mechanical ventilation or ventilation-free days. Conclusion: This study shows that a positive respiratory virus panel is associated with increased length of hospital stay. Early diagnosis of chronic obstructive pulmonary disease exacerbation patients with positive viral panel would help identify patients with a longer length of stay.

No association between BCR-ABL1 fusion genes and clinical features of acute lymphoblastic leukaemia in Ghanaian patients

INTRODUCTION: The BCR-ABL1 fusion gene has been associated with poor prognosis in acute lymphoblastic leukaemia (ALL). This study was designed to determine the presence, frequency and associated laboratory and clinical features of the BCR-ABL1 gene in Ghanaian patients diagnosed with ALL. METHODS: this was a cross-sectional study using archival methanol-fixed bone marrow aspirate slides of morphologically diagnosed ALL patients. Presence of the BCR-ABL1fusion gene was determined by fluorescent in situ hybridization. Clinical features and haematological parameters were extracted from the patients´ medical records. RESULTS: seventeen patients were studied, 13 (76.5%) males and 4 (23.5%) females. Median age was 24 years (range 15 to 67 years). A frequency of 29.4% was obtained for the BCR-ABL1 fusion gene. There was no significant association between presence of BCR-ABL1 and selected clinical features (lymphadenopathy, splenomegaly and hepatomegaly). All patients had moderate to severe anaemia with median haemoglobin concentration of 7.6 g/dL (range 3.7 to 8.7 g/dL). Median haemoglobin concentration for BCR-ABL1 positive patients was higher than that for negative patients (7.6 vs. 7.4 g/dL, p = 0.506); who also had higher median white blood cell counts (24.76 vs. 13.02 X 109/L), but lower median platelet counts (58.0 vs. 64.5 X 109/L, p = 0.721) and bone marrow blast percentages (78.5 vs. 98.0 %, p = 0.851) compared to negative patients. Conclusion: BCR-ABL1 fusion gene was detected in nearly one third of adult ALL patients in this study, with no significant association with common haematological parameters and clinical features of the disease.

Characteristics of Hospitalized Rhinovirus-Associated Community-Acquired Pneumonia in Children, Finland, 2003-2014.

Background: Rhinovirus (RV) is the most common cause of respiratory tract infections in children but, still, the clinical characteristics of RV-associated pneumonia have not been sufficiently investigated.Methods: We identified children and adolescents younger than 18 years of age treated for community-acquired pneumonia as inpatients at the Turku University Hospital from 2003 to 2014 and analyzed for RV by PCR of a respiratory tract specimen. We collected the data from medical records and compared RV-positive children with RV-negative children.Results: Of the study population of 313 children with pneumonia who were studied for RV, it was detected in 82 (26%). RV-positive children were younger (median age 2.6 years, interquartile range [IQR] 1.1–4.6 vs. 3.5 years, IQR 1.7–8.3, p = 0.002) and they had more often a history of preterm birth (16% vs. 5%, adjusted odds ratio 2.89, 95% confidence interval 1.21–6.92, p = 0.017) than RV-negative children. RV-positive children had a higher median white blood cell count than RV-negative children at presentation with pneumonia. The signs, symptoms, and severity of pneumonia were mostly similar in RV-positive and RV-negative children.Conclusions: RV was frequently detected in young children hospitalized with community-acquired pneumonia. We identified premature birth as a factor associated with RV-positive pneumonia. The clinical features of pneumonia did not clearly differ between RV-positive and RV-negative children. Further studies are needed to clarify the clinical significance of detection of RV in children with pneumonia.

488. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridium difficile Infection in Critically Ill Patients

BackgroundThere remains a paucity of data regarding optimal treatment of patients with severe Clostridium difficile infection (CDI) in the intensive care unit (ICU). Based on expert opinion, the 2018 SHEA-IDSA CDI Clinical Practice Guidelines recommend combination therapy (oral vancomycin [PO VAN] plus intravenous metronidazole [IV MDZ]) in fulminant CDI only. A 2015 study suggested a mortality benefit with combination therapy of PO VAN plus IV MDZ for ICU patients regardless of severity. The objective of this study was to determine the impact of combination therapy on clinical outcomes in ICU patients with severe CDI, compared with PO VAN monotherapy.MethodsSingle-center, retrospective, cohort of adult patients admitted to an ICU between April 2016 and April 2018 with a positive C. difficile nucleic acid amplification test and an order for PO VAN were screened for inclusion. Patients were excluded if they had life-threatening intra-abdominal complications, including toxic megacolon/emergent colectomy. The primary outcome was 30-day in-hospital all-cause mortality. In a subgroup analysis, patients were matched using Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Logistic regression was conducted to identify clinical variables associated with mortality.ResultsOne hundred one patients were included; 47 received combination therapy with IV MDZ. Baseline characteristics were similar across groups, except patients in the IV MDZ group had a higher median white blood cell (WBC) count at diagnosis (18.4 vs. 13.9, P = 0.023) and were more likely to receive a higher dose (500 mg) of PO VAN (36.2% vs. 7.4%, P < 0.0001). Thirty-day mortality was 14.9% in the combination group vs. 7.4% in the monotherapy group, (P = 0.338). APACHE II Score was the only variable independently associated with 30-day mortality (OR = 1.13, 95% CI 1.03 – 1.24). There was no difference in probability of receiving IV MDZ based on APACHE II score. In a subgroup of patients matched by APACHE II score (n = 76), mortality remained nonsignificantly different (15.8% vs. 9.7%, P = 0.480).ConclusionOur data question the utility of IV MDZ in addition to PO VAN for ICU patients with severe CDI. There remains a possibility for confounding by indication in this retrospective analysis.Disclosures E. Heil, ALK-Abelló: Grant Investigator, Research grant. K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee.

Prognostic significance of B-cell lymphoma 2 expression in acute leukemia: A systematic review and meta-analysis.

A number of studies have provided estimates of the correlation between B-cell lymphoma 2 (Bcl-2) expression and its clinical significance in acute leukemia (AL); however, the results have been heterogeneous. In order to clarify the prognostic significance of Bcl-2 status in patients with AL, a systematic review and meta-analysis of 5 published studies including a total of 665 subjects was performed. The reported frequency of Bcl-2 expression was 0-99.00%. Bcl-2-positive patients had a higher median white blood cell count compared to Bcl-2-negative patients. Additionally, Bcl-2-negative patients had >2-fold higher odds of achieving complete remission (CR) compared to Bcl-2-positive patients. The summary hazard ratio of Bcl-2 negativity/positivity for CR was 0.62 [95% confidence interval: 0.53-0.81, P<0.001]. Although this meta-analysis was based on data abstracted from observational studies, our results may justify the use of risk-adapted therapeutic strategies for AL according to the Bcl-2 expression status.

Incidence and Significance of Prostatic Stones in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Prostatic calcification is common in asymptomatic elderly men. However, young men with chronic pelvic pain syndrome (CPPS) often have significantly calcified prostates. We studied the incidence and significance of prostatic calcification in men with CPPS. From July 2005 to August 2006, 130 new patients with CPPS were seen at our clinic. Of these 130 patients, 47 underwent transrectal ultrasonography. Prostatic calcification correlated with symptoms (National Institutes of Health chronic prostatitis symptom index score), examination findings, and culture results. The variables were compared using the Student t test, Wilcoxon unpaired test, or chi-square test. The 47 men who had undergone transrectal ultrasonography had symptoms identical to those who had not but were older (range 46.1 to 41.6 years, P = 0.02) and had had symptoms longer (median 60 versus 12 months, P = 0.0001). Of the 47 patients, 22 (47%) had significant calcification. The symptoms with or without calcification were identical (chronic prostatitis symptom score 23.7 versus 23.9). Men with calcification had had symptoms longer (median 84 versus 27 months, P = 0.05) but were similar in age (49 versus 45 years, P = 0.21) and had a similar prostate size (21.7 cm3 for both groups). Men with calcification were less likely to have pelvic floor tenderness (50% versus 85%, P = 0.03) but were more likely to have bacteria in the prostatic fluid (P = 0.05) and had a higher median white blood cell count (3.5 versus 0 white blood cells per high power field, P = 0.058). Prostatic calcification is common in patients with CPPS and is associated with greater inflammation, bacterial colonization, and symptom duration. Pelvic floor spasm is more common in patients without calcification. This might be an important parameter with which to stratify clinical trials.

Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features

Although the occurrence of thrombosis in acute promyelocytic leukemia (APL) has been reported during retinoic acid treatment, no studies carried out in large clinical cohorts have specifically addressed this issue. We analyzed 124 APL patients treated with the all-trans retinoic acid and idarubicin protocol and compared clinico-biologic characteristics of 11 patients who developed thrombosis with those of 113 patients who had no thrombosis. In seven patients, the events were recorded during induction, whereas in four patients deep vein thrombosis occurred in the post-induction phase. Comparison of clinico-biological characteristics of patients with and without thrombosis revealed in the former group higher median white blood cell (WBC) count (17 x 10(9)/l, range 1.2-56, P=0.002), prevalence of the bcr3 transcript type (72 vs 48%, P=0.01), of FLT3-ITD (64 vs 28%, P=0.02), CD2 (P=0.0001) and CD15 (P=0.01) expression. No correlation was found with sex, age, French-American-British subtype, all-trans-retinoic acid syndrome or with thrombophilic state that was investigated in 5/11 patients. Our findings suggest that, in APL patients consistent biologic features of leukemia cells may predict increased risk of developing thrombosis.

CD10− Pre-B Acute Lymphoblastic Leukemia (ALL): A Distinct High-Risk Subgroup of Adult ALL.

Introduction: Immunological subtyping and molecular genetic analysis enable risk-adapted treatment of acute lymphoblastic leukemia (ALL). Translocations involving the mixed lingeage leukemia (MLL) gene characterize one poor-prognosis subtype of adult B-lineage precursor ALL correlating with a CD19+/CD10−/cytoplasmic (cy) IgM− immunophenotype (pro-B ALL).Patients and Methods: Immunophenotyping was performed on 2,408 newly diagnosed ALL specimens indentifying pro-B ALL, TdT+/CD19+/CD10−/cyIgM−/surface(S)Ig−; c-ALL, TdT+/CD19+/CD10+/cyIgM−/SIg−; and pre-B ALL, TdT+/CD19+/CD10+/cyIgM+/SIg−. Ambiguous cases of CD10-positivity (5–15% CD10-positivity) were rechecked by a second antibody. BCR-ABL RT-PCR and cytogenetics were performed. CD10-negative blasts also underwent MLL-AF4 RT-PCR. FISH using directly labelled probes for MLL was done in selected cases. Patients were treated according the German Multicenter Adult ALL trials (GMALL) with MLL-rearrangement positive patients treated in the high-risk arm.Results: Immunophenotyping identified 70 CD10-negative pre-B ALL specimens (TdT+CD19+cyIgM+). Fifty-six of these 70 CD10-negative pre-B ALL specimens contained a sufficient amount of blasts for molecular analysis. A total of 46/56 CD10-negative pre-B ALL were assigned to MLL-rearrangement positivity, revealing either MLL-AF4 fusion by RT-PCR (n = 38) or an 11q23/MLL translocation by cytogenetics (n = 4) or FISH (n = 4).Looking at clinical characteristics, MLL-rearrangement-positive patients were characterized by a higher median white blood cell count (P = .0002) and their blasts showed frequently neuroglial antigen 2 chondroitin sulfate proteoglycan (P = .02).Forty CD10− pre-B ALL patients with molecular genetic and/or cytogenetic data were evaluable for the treatment response and outcome. A complete remission (CR) was achieved in 6 of 7 (86%) MLL-rearrangement-negative and in 27 of 33 (82%) MLL-rearrangement-positive patients (P = .06). CR was maintained by 2 of 6 (33.3%) MLL-rearrangement-negative and 7 of 27 (26%) MLL-rearrangement-positive patients. The probability of remission duration after 3 years was 0.37 (± 0.29 SE) in MLL-rearrangement-negative versus 0.28 (± 0.13 SE) in MLL-rearrangement-positive patients contributing essentially to the overall survival at 3 years after diagnosis of 0.15 (± 0.06 SE) in patients with CD10-negative pre-B ALL.Conclusion: Our data identify CD10− cytoplasmic Ig-positive pre-B ALL as a rare (2.2%) but distinct immunosubtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome with conventional intensified treatment strategies.

Outcome of Philadelphia Chromosome-Positive Adult Acute Lymphoblastic Leukemia

Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) represents the most common cytogenetic abnormality in adult ALL. It is found in 15% to 30% of patients, and its incidence increases with age. As in children, prognosis in Ph-positive adult ALL is poor. No therapeutic approach has had substantial impact on its unfavorable course. We analyzed the characteristics and outcome of newly diagnosed adults with Ph-positive ALL treated at the M. D. Anderson Cancer Center between 1980 and 1997. The diagnosis of patients was based on typical morphological and immunophenotypic criteria of marrow aspirate and biopsy specimens. Cytogenetic and molecular studies were also performed. A total of 67 patients were included in this study. From 1980 until 1991, 38 patients with Ph-positive ALL were treated with vincristine, Adriamycin, and dexamethasone (VAD), or with acute myeloid leukemia (AML)-like induction protocols. Since 1992 a total of 29 patients received induction therapy with an intensified treatment protocol, called “hyper-CVAD”. The outcome of patients treated with standard and intensified treatment regimens was compared and results of our institution contrasted with data obtained from other centers.Ph-positive ALL was present in 67 of 498 patients with newly diagnosed ALL (13%). Patients with Ph-positive ALL had a higher median age (44 versus 34, P=0.007), higher median white blood cell (WBC) counts at presentation (25 versus 8, P=0.0002), and higher peripheral median percentage of blast counts (63 versus 40, P=0.023). FAB subtype L2 (70% versus 49%, P=0.001) and CALLA-positive pre-B immunophenotype (75% versus 37%, P<0.001) predominated among Ph-positive ALL. Myeloid marker coexpression was more frequent in Ph-positive ALL when compared with Ph-negative ALL (52% vs. 27% for CD13, P<0.001, and 44% vs. 27% for CD33, P=0.005). Among patients treated with hyper-CVAD, the complete remission (CR) rate was 90% versus 55% (P=0.002) with pre-hyper-CVAD regimens (VAD and AML-like induction protocols), the median CR duration was 43 weeks versus 32 weeks (P >0.5), median disease-free survival (DFS) was 42 weeks versus 29 weeks (P=0.008), and median survival was 66 weeks versus 45 weeks (P >0.5). Patients with hyper-diploid Ph-positive ALL on hyper-CVAD therapy achieved significantly longer CR duration and DFS than hypo- and pseudodiploid cases (59 weeks versus 42 and 31 weeks, P=0.02 and 0.04, respectively). In contrast, patients treated with regimens prior to hyper-CVAD had significantly shorter CR duration (21 weeks versus 33 and 29 weeks, P=0.03) and DFS with hyperdiploid karyotypes when compared to pseudodiploid and hypodiploid cases (16 weeks versus 30 and 13 weeks, P=0.008). In conclusion, our results demonstrate improved response rate and DFS with current intensive regimens (hyper-CVAD) in patients with Ph-positive ALL, but no advantage in overall survival.