Association Between a Common, Benign Genotype and Unnecessary Bone Marrow Biopsies Among African American Patients.

Importance: Up to two-thirds of African American individuals carry the benign rs2814778-CC genotype that lowers total white blood cell (WBC) count. Objective: To examine whether the rs2814778-CC genotype is associated with an increased likelihood of receiving a bone marrow biopsy (BMB) for an isolated low WBC count. Design, Setting, and Participants: This retrospective genetic association study assessed African American patients younger than 90 years who underwent a BMB at Vanderbilt University Medical Center, Mount Sinai Health System, or Children's Hospital of Philadelphia from January 1, 1998, to December 31, 2020. Exposure: The rs2814778-CC genotype. Main Outcomes and Measures: The proportion of individuals with the CC genotype who underwent BMB for an isolated low WBC count and had a normal biopsy result compared with the proportion of individuals with the CC genotype who underwent BMB for other indications and had a normal biopsy result. Results: Among 399 individuals who underwent a BMB (mean [SD] age, 41.8 [22.5] years, 234 [59%] female), 277 (69%) had the CC genotype. A total of 35 patients (9%) had clinical histories of isolated low WBC counts, and 364 (91%) had other histories. Of those with a clinical history of isolated low WBC count, 34 of 35 (97%) had the CC genotype vs 243 of 364 (67%) of those without a low WBC count history. Among those with the CC genotype, 33 of 34 (97%) had normal results for biopsies performed for isolated low WBC counts compared with 134 of 243 individuals (55%) with biopsies performed for other histories (P < .001). Conclusions and Relevance: In this genetic association study, among patients of African American race who had a BMB with a clinical history of isolated low WBC counts, the rs2814778-CC genotype was highly prevalent, and 97% of these BMBs identified no hematologic abnormality. Accounting for the rs2814778-CC genotype in clinical decision-making could avoid unnecessary BMB procedures.

Ethnic benign neutropenia: A phenomenon finds an explanation.

Ethnic benign neutropenia (ENP) is the most common form of neutropenia (NP) worldwide, if an absolute blood neutrophil count (ANC) of < 1.5 G/L is used as definition. In 2009, ENP was associated with a gene variation in the ACKR1/DARC gene, the same variation that also confers the Duffy-null trait. In 2017, a novel mechanism for ENP was introduced, questioning if ENP is a true neutropenic state, when the body's total neutrophil count (TBNC) is concerned. Here, we summarize the current knowledge of ENP, asking (1) How well does the peripheral blood ANC predict the TBNC? (2) Can we improve methods for assessing TBNC? (3) Will estimates of TBNC predict infection propensity and reduce the need for further, costly workup?

Analyses of genome wide association data, cytokines, and gene expression in African-Americans with benign ethnic neutropenia.

BACKGROUND: Benign ethnic neutropenia (BEN) is a hematologic condition associated with people of African ancestry and specific Middle Eastern ethnic groups. Prior genetic association studies in large population showed that rs2814778 in Duffy Antigen Receptor for Chemokines (DARC) gene, specifically DARC null red cell phenotype, was associated with BEN. However, the mechanism of this red cell phenotype leading to low white cell count remained elusive. METHODS: We conducted an extreme phenotype design genome-wide association study (GWAS), analyzed ~16 million single nucleotide polymorphisms (SNP) in 1,178 African-Americans individuals from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and replicated from 819 African-American participants in the Atherosclerosis Risk in Communities (ARIC) study. Conditional analyses on rs2814778 were performed to identify additional association signals on chromosome 1q22. In a separate cohort of healthy individuals with and without BEN, whole genome gene expression from peripheral blood neutrophils were analyzed for DARC. RESULTS: We confirmed that rs2814778 in DARC was associated with BEN (p = 4.09×10-53). Conditioning on rs2814778 abolished other significant chromosome 1 associations. Inflammatory cytokines (IL-2, 6, and 10) in participants in the Howard University Family Study (HUFS) and Multi-Ethnic Study in Atherosclerosis (MESA) showed similar levels in individuals homozygous for the rs2814778 allele compared to others, indicating cytokine sink hypothesis played a minor role in leukocyte homeostasis. Gene expression in neutrophils of individuals with and without BEN was also similar except for low DARC expression in BEN, suggesting normal function. BEN neutrophils had slightly activated profiles in leukocyte migration and hematopoietic stem cell mobilization pathways (expression fold change <2). CONCLUSIONS: These results in humans support the notion of DARC null erythroid progenitors preferentially differentiating to myeloid cells, leading to activated DARC null neutrophils egressing from circulation to the spleen, and causing relative neutropenia. Collectively, these human data sufficiently explained the mechanism DARC null red cell phenotype causing BEN and further provided a biologic basis that BEN is clinically benign.

Efficacy and Safety of Dapsone Versus Trimethoprim/Sulfamethoxazol for Pneumocystis Jiroveci Prophylaxis in Children With Acute Lymphoblastic Leukemia With a Background of Ethnic Neutropenia.

STUDY OBJECTIVE: To study dapsone in comparison with trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL). DESIGN: A retrospective study with a prospective follow-up. PATIENTS: Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia. METHODS: TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to dapsone. RESULTS: Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on dapsone. After shifting to dapsone, patients maintained significantly higher ANC (1.46±0.46 vs. 1.17±0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%±11.45 vs. 57.45±10.14, P=0.0081) and methotrexate (64.9%±14.29 vs. 56.5%±9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94±1.2 vs. 3.25±1.29 wk, P=0.0002). CONCLUSIONS: Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.

Identification and Clinical Characterization of Children With Benign Ethnic Neutropenia.

Benign ethnic neutropenia (BEN) is an asymptomatic condition reported in adults of African and Middle Eastern descent. The clinical description in children is currently lacking. In our urban outpatient pediatric hematology clinic, the median neutrophil count of children with BEN was lower than previous reports in adults at 893×10 cells/L, but increased with older age. There was an equal male to female ratio and 24% of our BEN children reported ethnicities other than African or Middle Eastern. Children with BEN had a clinical course comparable with other healthy children including otherwise normal blood counts, except for mild anemia.

[Benign ethnic neutropenia; an unrecognised cause of leukopenia in negroid patients]. / Benigne etnische neutropenie: een onbekende oorzaak van leukopenie bij negroïde patiënten.

Leukopenia has a high incidence and is usually a reason for additional testing. Benign ethnic neutropenia is a relatively common cause of neutropenia in the negroid population. It can be the cause of aberrant laboratory results in negroid patients. A 55-year-old woman from Ghana was referred to the outpatient clinic because of malaise, leukopenia and neutropenia. Viral infection, haematological malignancy, auto-immune disease and vitamin deficiency were considered, but could not be confirmed by additional testing. Upon further investigation, the neutropenia in this patient was found to have existed for years. Moreover, our patient's son also had asymptomatic leukopenia. Therefore, benign ethnic neutropenia was considered the most likely diagnosis. Serological analysis of the patient's erythrocytes revealed the absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b), which is associated with benign ethnic neutropenia.

Poikiloderma with neutropenia: report of three cases including one with calcinosis cutis.

Poikiloderma with neutropenia (PN), Clericuzio type (OMIM #604173) is a new, unique genodermatosis first described by Clericuzio et al (Am J Med Genet A, 2011, 155, 337) in Navajo Indian population. This disease is characterized by poikiloderma that usually develops in the first year of life and is associated with nail abnormality, palmoplantar hyperkeratosis, chronic neutropenia, and recurrent infections. The rash typically starts from the extremities and spreads centripetally to involve the trunk, face, and ears. Recently, a homozygous mutation in the C16orf57 gene on chromosome 16q13 was identified as a strong candidate as the gene responsible for PN. We report three cases of PN whose clinical presentations, laboratory investigations, and C16orf57 mutation support the diagnosis of PN. One child has developed multiple painful calcinosis cutis lesions. Early-onset poikiloderma should prompt a complete blood count as a screening test.

Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network.

PURPOSE: We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population. METHODS: We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts. RESULTS: From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score ≥ 21, 84% (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p < 0.0001). CONCLUSIONS: The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.

Ethnic and genetic causes of neutropenia: clinical and therapeutic implications.

The white blood cell count represents clinical data linked with different pathologic conditions, as well as with lifestyle. Another very important condition that affects the number of leukocytes is race and ethnic group-the geographic zone of origin. Genetic studies have identified the gene that controls the expression of the Duffy antigen receptor for chemokine (DARC), which is associated with the ethnic group to which individuals belong. The single-nucleotide polymorphism strongly associated with race is DARC rs2814778. Currently, it is the only condition that can explain the difference in white blood cell count between different ethnic groups. In a society increasingly characterized by multiracial issues, the leukopenia and/or neutropenia in ethnic groups must be known and accurately assessed clinically. Improved knowledge of this association may help in optimizing therapeutic approaches, mainly for African patients with severe diseases, cancer in particular. Recently, preclinical data have also suggested a link between the Duffy antigen and coagulation. This review also discusses the main causes of genetic neutropenia.

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

BACKGROUND: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica. METHODS: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism. RESULTS: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels. CONCLUSIONS: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.

Potential regional differences for the tolerability profiles of fluoropyrimidines.

PURPOSE: We conducted a retrospective analysis of safety data from randomized, single-agent fluoropyrimidine clinical trials (bolus fluorouracil/leucovorin [FU/LV] and capecitabine) to test the hypothesis that there are regional differences in fluoropyrimidine tolerability. METHODS: Treatment-related safety data from three phase III clinical studies were analyzed by multivariate analysis: two comparing capecitabine with bolus FU/LV in metastatic colorectal cancer (MCRC) and one comparing capecitabine plus oxaliplatin (XELOX) with bolus FU/LV as adjuvant treatment for colon cancer. The United States (US) was compared with non-US countries (all three studies) and with the rest of the world and East Asia (adjuvant study). RESULTS: In the MCRC studies (n = 1,189), more grade 3/4 adverse events (AEs; relative risk [RR], 1.77), dose reductions (RR, 1.72), and discontinuations (RR, 1.83) were reported in US versus non-US patients. Likewise, in the adjuvant colon cancer study (n = 1,864), more grade 3/4 AEs (RR, 1.47) and discontinuations (RR, 2.09) were reported in US versus non-US patients. After further dividing non-US patients into those in East Asia and the rest of the world, differential RRs for related grade 3/4 AEs, grade 4 AEs, and serious AEs were again observed, with East Asian patients having the lowest and US patients the highest RR. CONCLUSION: Regional differences exist in the tolerability profiles of fluoropyrimidines. More treatment-related toxicity was reported in the US compared with the rest of the world for bolus FU/LV and capecitabine in first-line MCRC and adjuvant colon cancer. In the adjuvant setting, a range of fluoropyrimidine tolerability was observed, with East Asian patients having the lowest, and US patients the highest, RR.

White blood cell counts in healthy Jamaican adults / Conteo de glóbulos blancos en adultos jamaicanos sanos

The investigation of presumed neutropenia places a burden on the health services, especially those of developing countries, including Jamaica. This may be because the normal ranges used in the laboratory are based on the values generated from the Caucasian population. Previous studies looking at African and Afro-Caribbean groups have found lower counts for these populations compared with Caucasians. To address this issue, 195 healthy adults donating blood at the National Public Health Laboratory and the University Hospital of the West Indies blood banks in Kingston, Jamaica, were screened for complete blood count (CBC) differentials between June 2001 and June 2006. The geometric means for the neutrophil counts were found to be 2.4 x 10(9)/L for men and 2.7 x 10(9)/L for women, with 95% confidence intervals of 2.2-2.8 x 10(9)/L and 2.5-3.1 x 10(9)/L respectively. Values for the Jamaican population were similar to those of other Afro-Caribbean groups. Based on this distribution, 14% of healthy Jamaicans would fall below the normal ranges derived from Caucasians and therefore presumed to have neutropenia. We recommend that the lower reference ranges obtained for Afro-Caribbean adults be adopted for that population.

La investigación de una neutropenia presunta, representa una carga para los servicios de salud, sobre todo en los países en vías de desarrollo, incluyendo Jamaica. La razón de ello puede estribar en que los rangos normales usados en el laboratorio, se basan en valores generados a partir de la población caucásica. Estudios previos sobre los grupos africanos y afro-caribeños, han hallado conteos más bajos para estas poblaciones, en comparación con las caucásicas. A fin de abordar este problema, 195 adultos sanos que donaron sangre al Laboratorio Nacional de Salud Pública y a los bancos de sangre del Hospital Universitario de West Indies en Kingston, Jamaica, fueron tamizados en busca de diferenciales en conteos completos de sangre (CCS), entre junio de 2001 y Junio de 2006. Para los conteos de neutrófilos, se halló que las medias geométricas fueron 2.4 x 10(9)/L para los hombres y 2.7 x 10(9)/L para las mujeres, con intervalos de confianza del 95% equivalentes a 2.2-2.8 x 10(9)/L y 2.5-3.1 x 10(9)/L respectivamente. Los valores para la población jamaicana fueron similares a los de otros grupos afro-caribeños. Sobre la base de esta distribución, el 14% de los jamaicanos saludables caerían por debajo de los rangos normales derivados a partir de los caucásicos, y por consiguiente se presumiría que tienen neutropenia. Nosotros recomendamos que los rangos de referencia más bajos obtenidos para los adultos afro-caribeños sean adoptados para esa población.

PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.

Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.

Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences.

BACKGROUND: Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status. OBJECTIVE: To determine differences in neutrophil counts in the U.S. population according to ethnicity, age, sex, and smoking status. DESIGN: Population-based, cross-sectional study. SETTING: Various locations in the United States. PARTICIPANTS: 25,222 participants in the 1999 to 2004 National Health and Nutrition Examination Survey who were 1 year of age or older. MEASUREMENTS: Complete blood counts and comparison of means and the proportion of participants with neutropenia. RESULTS: Relative to white participants, black participants had lower leukocyte counts (mean difference, 0.89 x 10(9) cells/L; P < 0.001), lower neutrophil counts (0.83 x 10(9) cells/L; P < 0.001), and similar lymphocyte counts (0.022 x 10(9) cells/L; P = 0.36), whereas Mexican-American participants had slightly higher mean leukocyte counts (0.16 x 10(9) cells/L; P = 0.014), higher neutrophil counts (0.11 x 10(9) cells/L; P = 0.026), and higher lymphocyte counts (0.095 x 10(9) cells/L; P < 0.001). The prevalence of neutropenia (neutrophil count <1.5 x 10(9) cells/L) was 4.5% among black participants, 0.79% among white participants, and 0.38% among Mexican-American participants. The prevalence of neutropenia was higher among males and children younger than 5 years of age. Neutrophil counts less than 1.0 x 10(9) cells/L were observed in fewer than 1% of the overall sample (0.57% in black participants, 0.11% in white participants, and 0.08% in Mexican-American participants). Smoking was associated with higher leukocyte and neutrophil counts but had a smaller effect among black and Mexican-American participants than among white participants. LIMITATION: Because estimates are based on single measures, fluctuations over time could not be determined. CONCLUSIONS: In the United States, neutrophil counts are lower in black persons than in white persons and neutropenia is more prevalent in black persons. Neutrophil counts are slightly higher in Mexican-American persons than in white persons, and neutropenia is uncommon in both groups. The clinical implications of these findings are unclear, but they suggest that when determining the need for a diagnostic evaluation for neutropenia, clinicians should consider the patient's age, sex, ethnicity, and smoking status.

Causes of incidental neutropenia in adulthood.

The incidental discovery of neutropenia during routine blood counting represents a common problem for clinicians. However, there are no reported data of systematic evaluations of adults with incidental neutropenia. As such, this was the aim of the present study. Ninety-seven adults with incidental neutropenia were submitted to a clinical and laboratory approach including medical evaluation, complete blood count (CBC), serial CBC, direct and indirect antiglobulin test, bone marrow smear and biopsy, assessment of folate, vitamin B12 and iron status, serum liver enzymes, serum proteins, serological exams for hepatitis B and C virus, cytomegalovirus, mononucleosis, human immunodeficiency virus and toxoplasmosis, detection of lupus erythematosus cells, antinuclear and anti-DNA antibodies and rheumatoid factor, dosage of free thyroxin and thyrotropin, chest roentgenogram and abdominal echography. Chronic idiopathic neutropenia of adults was identified in 34.0% of the individuals, neutropenia due to exposure to chemical agents was seen in 16.5%, infectious diseases in 9.3%, autoimmune diseases in 9.3%, haematological diseases in 9.3%, thyroid disorders in 8.2%, ethnic neutropenia in 7.2%, drug-related neutropenia in 2.1%, cyclic neutropenia in 2.1% and iron deficiency in 2.1%. Recovery or improvement of the neutrophil count was seen upon treatment or recuperation from infectious, autoimmune, haematological and thyroid diseases and iron supplementation. We conclude that the evaluation of individuals with incidental neutropenia using a structured approach may make the identification of clinically silent diseases possible, and provide an opportunity for early treatment, avoiding complications of the diseases and consequences of neutropenia.

Hematologic findings in children with rotavirus-positive and -negative diarrhea.

The authors studied neutropenia in 101 children hospitalized for gastroenteritis between 1 December 2000 and 30 June 2001 and identified children tested for rotavirus by reviewing their laboratory records. Rotavirus-positive and rotavirus-negative subjects did not differ significantly in their white blood cell counts, absolute neutrophil counts, or frequency of neutropenia (defined as an absolute neutrophil count < 1.0 x 10(9)/L), which accompanied 8.6% of rotavirus-positive cases and 9.3% of rotavirus-negative cases of gastroenteritis. The authors conclude that mild neutropenia accompanying diarrhea does not require further evaluation unless it persists or is associated with other factors such as sepsis.