Modeling administrative outcomes in fever and neutropenia: clinical variables significantly influence length of stay and hospital charges

BACKGROUND: Administrative outcomes such as length of stay and charges are used to compare the quality of care across institutions and among individual providers. Clinical variables representing disease severity may explain some of the variability in these outcomes. OBJECTIVE: To determine the extent to which readily available clinical data can explain the variability in length of stay and charges for children with cancer admitted to the hospital for fever and neutropenia, and to assess the appropriateness of using a time-efficient electronic case-finding strategy for the development of administrative outcome models. METHODS: A retrospective cohort of 157 fever and neutropenia encounters in a single institution during 11 months in 1997 was identified using a largely automated case-finding strategy followed by independent, blinded review of the selected discharge summaries. Models of admission variables predicting log length of stay and log charges were developed using multiple linear regression. The "smearing" technique of Duan adjusted for logarithmic retransformation was used in calculating each subject's predicted length of stay and charges. R2 values were calculated. There were two secondary analyses. In one, the result of admission blood culture was entered as a potential covariate. In the second, to evaluate the appropriateness of basing models on automated case-finding without discharge summary review, the authors rederived the models using all of the encounters (n = 160) identified by the algorithm, which had included three false-positive cases. RESULTS: Mean length of stay was 6.45 days. Mean charges were $11,967. Absolute monocyte count at admission was a significant, independent negative predictor of length of stay and charges. Underlying cancer diagnosis also was significant. Charges were highest for acute myeloid leukemia, followed by central nervous system tumors, other solid tumors, and acute lymphoblastic leukemia and lymphomas. Length of stay was highest for acute myeloid leukemia, followed by central nervous system tumors, acute lymphoblastic leukemia and lymphomas, and other solid tumors. Absolute monocyte count and tumor type were the major components of the model, but admission temperature (for both administrative outcomes) and the presence of localized infection (for length of stay) also were significant predictors. R2 values were 35.3% (charges) and 38.5% (length of stay), with validation R2 values of 26.6% and 29.2%, respectively. Entering bacteremia as a covariate improved the models. Inclusion of the three false-positive cases generated models with only a modest loss of accuracy; it introduced over-and underreporting of some of the less significant predictors but did not disrupt the ability to identify the major predictors, absolute monocyte count and tumor type. CONCLUSIONS: The clinical variables that were significant in this study account, in validation R2 estimates, for more than 25% of the variability in administrative outcomes for encounters of fever and neutropenia. Adjusting length of stay and charges for these clinical variables would allow for a fairer comparison of institutions and individual providers. The electronic case-finding algorithm served as an efficient way to identify absolute monocyte count and tumor type as the major predictors and provided a conservative estimate of R2.     

Features and outcome of neonatal leukemia in Japan: experience of the Japan infant leukemia study group

BACKGROUND: Neonatal leukemia characterized by early stem cell origin and extramedullary infiltration in the first 4 weeks of life is rare. We analyzed the features and outcome of neonatal leukemia in Japan to establish an appropriate treatment strategy for this rare disorder. PROCEDURE: Patients with infant leukemia registered and treated in the Japan Infant Leukemia Study between 1996 and 2001 were analyzed. RESULTS: Among 162 infant leukemia patients, 11 exhibited neonatal leukemia; frequencies for all infant leukemias were 6.9% (8/116) for acute lymphoblastic leukemia (ALL) and 7.3% (3/41) for acute myeloid leukemia (AML). Positive MLL gene rearrangement was observed in all eight patients with ALL; a single patient with AML displayed germline configuration. Acute monoblastic leukemia was apparent in all three patients with AML (M5a in the FAB classification). Most of the patients demonstrated hepatoplenomegaly and hyperleukocytosis at diagnosis. Cutaneous and central nervous system involvement were detected in half of the patients. Four patients (one with AML, and three with ALL) have survived following stem cell transplantation (SCT); however, growth impairment related to SCT was observed in these patients. CONCLUSIONS: These results suggest an improvement attributable to treatment of neonatal leukemia. International-based collaborative studies are necessary to investigate the biology of this condition and to establish appropriate therapeutic strategies.     

Successful acute lymphoblastic leukemia‐type therapy in two children with mixed‐phenotype acute leukemia

Mixed‐phenotype acute leukemia (MPAL) is a rare type of leukemia expressing both myeloid and lymphoid markers. There is limited information, especially on pediatric cases. Therefore, the optimal therapeutic approach to pediatric MPAL has not been defined. Here, we report two pediatric cases of MPAL. According to the 2008 World Health Organization (WHO) classification and European Group for the Immunological Characterization of Leukemias (EGIL) criteria, patient 1 was diagnosed with overt MPAL positive for the myeloid marker myeloperoxidase (MPO), and B‐lymphoid markers. Patient 2 was diagnosed with T‐cell acute lymphoblastic leukemia (T‐ALL) using EGIL criteria. According to the 2008 WHO classification, however, patient 2 was diagnosed with overt MPAL positive for CD3, T‐lymphoid markers and MPO. We chose an ALL‐type therapy consisting of both lymphoid‐ and myeloid‐directed agents; these patients have maintained complete remission following treatment. Further information on pediatric MPAL is needed to establish an appropriate therapeutic strategy including stem cell transplantation for this rare condition.     

Extramedullary myeloid tumors in children: the limited value of local treatment

PURPOSE: To determine the incidence of extramedullary tumors (EMT) in Saudi Arabian children with acute myeloid leukemia, the factors associated with these tumors and the impact of local treatment on local tumor control, complete remission and survival rates. PATIENTS AND METHODS: One hundred children, median age 6 years, who received their primary treatment for acute myeloid leukemia at King Faisal Specialist Hospital and Research Center, from 1983 to 1997 were studied. EMT at diagnosis occurred in 18 (18%) patients at 25 sites. Meningeal leukemia, hepatosplenomegaly, lymph node enlargement, gingival hypertrophy, and cutaneous infiltration were not included in the definition of EMT. With these exclusions, children with EMT were younger than those without EMT (median age, 3.5 v. 7.5 years) and were more likely to have meningeal leukemia at diagnosis (33% v. 10%). The t(8;21) translocation was associated with a 47% EMT incidence compared with 23% without the translocation. Local radiation treatment was given to 16 of 25 (64%) EMT sites. RESULTS: The overall 5-year survival rate for all patients was 28%, and this was not significantly influenced by the drug regimen used, meningeal leukemia at diagnosis, the presence of the (8;21) translocation, M4 and M5 morphology combined, or EMT at diagnosis. Significant differences were observed in the 5-year survival rates for patients who underwent allogeneic bone marrow transplantation (52%; N = 37) and those who attained complete remission (CR) but did not undergo transplantation (21%; N = 44) and those who did not achieve complete remission with initial therapy (5%; N = 19). Systemic and local EMT CR was achieved in 17 of 18 patients with EMT, including 12 patients who underwent radiation treatment and 5 of 6 of those who did not. Isolated relapse was not seen at an EMT site and was not noted at any later stage of the disease. CONCLUSIONS: Permanent local control at sites of EMT was achieved in all patients who attained a bone marrow CR, whether or not the site was irradiated. Local radiation treatment of an EMT site did not appear to contribute to overall CR and survival rates. The use of radiation treatment should be conservative and limited to patients in whom there is a real and immediate threat to vision or renal function or when the spinal cord is compromised.     

Risk score for pediatric intensive care unit admission in children undergoing hematopoietic stem cell transplantation and analysis of predictive factors for survival

The authors retrospectively analyzed postransplantation events in 198 children who underwent hematopoietic stem cell transplantation (HSCT) between 1998 and 2002 to obtain a risk score for pediatric intensive care unit (PICU) admission and to ascertain variables predicting a poor outcome. Thirty-six patients (18%) were admitted to the PICU. Median age was 9 years (range 1-18). On univariate analysis, variables significantly associated with PICU admission were male gender (P = 0.01), more than first complete remission (P = 0.003), allogeneic transplantation (P = 0.001), engraftment syndrome (P = 0.03), and acute graft-versus-host disease grade of at least two (P = 0.05). According to this, patients were divided in two levels of risk (low and high), with a respective probability of PICU admission of 8.8 +/- 2.2% and 63.8 +/- 8.8% (P < 0.0001). Seventeen (47%) patients were discharged from the PICU. The probability of event-free survival after PICU admission at 3 years was 24.2 +/- 7%. On univariate analysis, variables with a negative impact on event-free survival were type of transplantation, inotropic support, a C-reactive protein level of at least 10 mg/dL, and a high O-PRISM score. On multivariate analysis, the only variable that influenced event-free survival was the O-PRISM score (< or =10 points, 54.6 +/- 15.3%; >10 points, 8.6 +/- 5.8%; P = 0.007). In conclusion, the risk of PICU admission may be easily estimated using simple variables. A high O-PRISM score at the time of PICU admission predicts a dismal outcome.     

PICU侵袭性真菌感染现状

PICU侵袭性真菌感染（ invasive fungal infection,IFI）呈现逐年升高趋势。念珠菌和曲霉是最常见的病因,儿童重症侵袭性念珠菌感染（ ICI）发病率约为侵袭性曲霉感染（ IAI）的5倍。ICI和IAI归因死亡率有所不同,主要是基础疾病存在差异。既往健康的危重症患儿各种侵入性导管、静脉营养、血液透析、机械通气和长时间使用抗生素是ICI发病危险因素。实体肿瘤和白血病患儿使用免疫抑制剂、干细胞移植和广谱抗生素是发生IAI的高危因素。对高风险患儿采取针对性预防,早期识别IFI并予以抢先治疗,仍然是管理PICU危重症患儿的重要挑战。     

Short‐term and long‐term mortality following pediatric intensive care

Background: The aim of the present study was to examine short‐term and long‐term mortality following discharge from the pediatric intensive care unit (PICU). Methods: This was a prospective observational study. Data collected consisted of demographics, severity scores, procedures, treatment, need for and duration of mechanical ventilation (MV), length of PICU and hospital stay, and mortality at PICU and hospital discharge, at 3 and 6 months and at 1 and 2 years. Results: A total of 300 patients (196 boys and 104 girls), aged 54.26 ± 49.93 months, were included in the study. Median (interquartile range) Pediatric Risk of Mortality (PRISM III‐24) score was 7 (3–11) and predicted mortality rate was 11.16%. MV rate was 67.3% (58.3% at admission) for 6.54 ± 14.15 days, and length of PICU and hospital stay was 8.85 ± 23.28 days and 20.69 ± 28.64 days, respectively. Mortality rate at discharge was 9.7% and cumulative mortality rate thereafter was 12.7%, 15.0%, 16.7%, 19.0%, and 19.0% at hospital discharge, 3 months, 6 months, 1 year and 2 years, respectively. Significant risk factors of PICU mortality were inotrope use, PRISM III‐24 score >8, MV, arterial and central venous catheterization, nosocomial infection, complications, and cancer. Independent predictors of mortality at discharge were inotrope use and PRISM III‐24 score, whereas predictors of mortality at 2 years were comorbidity and cancer. Conclusions: A 2 year follow‐up period seems sufficient for a comprehensive mortality analysis of PICU patients. Severity of critical illness is the key factor of short‐term mortality, whereas comorbidity is the major determinant of long‐term mortality.     

Costs, charges, and reimbursements for persons with sickle cell disease.

PURPOSE: The aims of this study were to describe health care costs and charges for patients with sickle cell disease (SCD) and identify predictors of high use. PATIENTS AND METHODS: Patients with SCD were identified by International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes from a university hospital's administrative databases from January 1, 1996, to September 30, 1997. Clinical and administrative data were gathered on each patient for all hospital admissions and ambulatory clinic visits. Logistic regression models were used to determine predictors of high health care use. RESULTS: A total of 947 patients with SCD were identified, 73% of whom resided within three South Carolina counties. On average, there were 0.9 admissions per patient per year and 8.0 outpatient visits per patient per year. Mean inpatient hospital charges, physician charges, and direct hospital costs per admission were $7290, $1589, and $5405, respectively, and the average length of stay was 4.5 days. Mean hospital charges, physician charges, and direct hospital costs per outpatient visit were $305, $169, and $688, respectively. Forty percent of the inpatient hospital charges were accounted for by only 4.2% of the patients. Residing in a distant county and being admitted with a diagnosis of painful respiration were found to be predictors of excessive charges and expenses beyond expected reimbursements. CONCLUSIONS: Patients with SCD are frequent users of health care services. Charges and costs are distributed disproportionately across these patients. Predictors of excessive hospital charges include living geographically distant from the hospital and being admitted with a diagnosis of painful respiration.     

Differentiating juvenile myelomonocytic leukemia from chronic myeloid leukemia in childhood

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disease of early childhood. To determine the diagnostic features, appropriate treatment, and overall patient survival pertaining to JMML for children, the authors reviewed the clinical data of 16 children with JMML admitted to the National Taiwan University Hospital between 1978 and 2001. Median age at diagnosis was 2.5 years. Fever was the most common symptom at diagnosis. At initial presentation, the mean white blood count and absolute monocyte count were 30 x 10(9)/L and 4.5 x 10(9)/L, respectively. Cytogenetic analysis was performed in 14 patients, and 2 patients (14%) had monosomy 7. Another patient, with normal karyotype at diagnosis, had deletion of 7q22 at the follow-up chromosome study. Forty-seven chronic myeloid leukemia (CML) patients were also diagnosed and followed at the same hospital during the same interval period. The age, leukocyte counts, platelet counts, basophil counts, monocyte percentages on peripheral blood smears, and median survival rate showed significant differences between JMML and CML patients (P < 0.05). The median survival was 10 months and the probability of 10-month survival was 0.38 by Kaplan-Meier analysis for 12 of the 16 JMML patients who did not receive hematopoietic stem cell transplantation (HSCT). Among three patients receiving HSCT, one patient relapsed 9 months after the first HSCT and was treated successfully by a second HSCT from the same sibling donor.     

Infant acute lymphoblastic leukemia: a 20-year children's hospital experience

We reviewed our 20-year experience with infant acute lymphoblastic leukemia (ALL). Nine infants (4.2% of all ALL) were identified; all were < 6 months of age. White blood cell counts ranged from 42,000-1.6 million/microL, 6 of 8 had hepatosplenomegaly, and 6 of 9 (66.6%) had central nervous system disease. Of 7 with cytogenetic information, 6 (85.7%) had diploidy; the remaining child was 47, XY,+8,del(21)(q22). Four had the MLL-11q23 abnormality. All received chemotherapy. Four underwent stem cell transplantation. Survival was 67%, (15 months-21 years). Deaths occurred at 9 months, 15 months (graft vs. host), and 7 years (complications of small bowel transplantation). Only 1 undergoing stem cell transplantation died. There were no late recurrences or second malignancies. Despite extensive disease and age < 6 months at diagnosis (a poor prognostic feature), for ALL patients our 67% survival is at least as good as reported, although it is less favorable than childhood ALL.     

Allogeneic stem cell transplantation for children with acute myeloid leukemia in second complete remission

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for patients with relapsed acute myeloid leukemia. In this retrospective, multicenter study, we analyzed the outcome of 63 children (median age, 7 y; range, 0.2 to 17) who received unmanipulated allo-HSCT in second complete remission. Either a matched family donor or an unrelated donor was used in 29 (46%) and 34 (54%) patients, respectively. The stem cell source was bone marrow in 53 children (84%), peripheral blood in 7 (11%), and cord blood in 3 patients (5%). Preparative regimen included total body irradiation in 25 patients (40%). The 5-year estimates of overall survival and leukemia-free survival were 53% [95% confidence interval (CI) 39-66] and 49% (95% CI 35-63), respectively, whereas the cumulative incidence of relapse and transplant-related mortality (TRM) were 26% (95% CI 16-41) and 25% (95% CI 15-40), respectively. In multivariate analysis, the use of a matched family donor predicted a better probability of LFS [relative risk (RR) 2.29, P=0.05]. Both chronic graft-versus-host disease occurrence and age at diagnosis greater than 11 years were associated with an increased TRM (RR 8.08, P=0.04 and RR 4.38, P=0.05, respectively). These results indicate that allo-HSCT is a procedure able to rescue a significant proportion of children with acute myeloid leukemia in second complete remission, especially if an human leukocyte antigen-compatible relative is employed as donor. Both leukemia recurrence and TRM contributed to treatment failure. Optimization of donor selection and of strategies for both prophylaxis and treatment of graft-versus-host disease may improve the results of unrelated donor allo-HSCT.     

An unusual case of acute myeloid leukemia: Late isolated testicular relapse followed by isolated central nervous system relapse

Testicular relapse of acute myeloid leukemia without bone marrow involvement is a rare event. We describe a case of an 18‐year‐old male who had an isolated testicular relapse 86 months (7.2 years) from original diagnosis. He was treated with surgery only, without adjuvant therapy. The patient then developed central nervous system involvement 9 months later. Fluorescence in situ hybridization and immunohistochemistry were used to establish the diagnosis of a relapse rather than a new leukemic process. He was treated with intrathecal chemotherapy and systemic reinduction, followed by a stem cell transplant. This patient had a 7.2‐year period between original diagnosis and the testicular relapse of acute myeloid leukemia. Pediatr Blood Cancer. 2010;55:1231–1233. © 2010 Wiley‐Liss, Inc.     

��ͯ˫���Ͱ�Ѫ�����ٴ�������Ԥ�����

目的分析儿童双免疫表型白血病的临床及生物学特征,评价儿童急性白血病双免疫表型与治疗相关因素及预后的临床重要性。方法自1998年1月1日至2003年5月31日进入XH99治疗方案的所有新诊治的急性白血病(AL)患儿,诊断采用MICM分型诊断,治疗分别按AMLXH99、ALLXH99危险度分类标准进行分层治疗。用流式细胞仪进行免疫表型分析,根据免疫表型结果将患儿分为4组,伴有/无髄系相关抗原表达的急性淋巴细胞白血病(My+ALL/My-ALL)以及伴有/无淋系相关抗原表达的急性髓系白血病(Ly+AML/Ly-AML)。生存分析采用KaplanMeier方法;生存率之间的比较采用logrank检验;临床及生物学特征与治疗相关因素的分析采用χ2检验或Fisher精确概率法(双尾)。结果①174例提供免疫分型的ALL患儿中,My+ALL患儿34例,占19.54%,其与My-ALL组患儿除在BALL组患儿达缓解时间有统计学差异外(P<0.05),其它临床、生物学特征及治疗反应均无统计学差异(P>0.05);两组患儿5年无事件生存(EFS)率分别为[(61.76±8.33)%与(68.03±5.55)%],logrank检验两组患儿5年EFS率无统计学差异(P=0.0526)。②74例提供免疫分型结果的AML患儿中,Ly+AML患儿18例,占24.32%,其与Ly-AML组患儿临床、生物学特征及治疗反应无统计学差异(P>0.05);两组患儿5年EFS率分别为[(39.82±13.59)%与(51.29±9.70)%],logrank检验两组患儿5年EFS率无统计学差异(P=0.3164)。结论双免疫表型对儿童白血病预后无明显影响,可用同样现行的化疗方案治疗这部分患儿。     

Childhood leukemia and lymphoma: correlation of clinical features with immunological and morphological studies

Malignant cells from 49 children with lymphoid neoplasms other than Hodgkin disease were evaluated by surface marker and morphologic studies. We classified the patients into three groups: 36 patients (74%) with acute lymphocytic leukemia; 7 (14%) classified as convoluted lymphocytic lymphoma/leukemia; and 6 (12%) with small noncleaved follicular center cell lymphoma/leukemia. Diffuse marrow involvement was present at diagnosis in some patients in the latter two groups, but their clinical course was not characteristic of the patients with acute lymphocytic leukemia. Male predominance, poor prognosis, and high incidence of central nervous system disease characterized patients in the convoluted lymphocytic and follicular center cell lymphoma/leukemia groups. Clinical presentation in these two groups differed. Proliferations of convoluted lymphocytes were associated with mediastinal masses and proliferations of follicular center cells with intraabdominal tumors. The high incidence of CNS disease in children with neoplasms of convoluted lymphocytes and follicular center cells suggests that these processes have a predilection for the CNS and that patients with them may benefit from CNS prophylaxis.     

儿童造血干细胞移植并发出血性膀胱炎的危险因素分析与防治研究

目的观察儿童造血干细胞移植（HSCT）中出血性膀胱炎（HC）的发病情况,探讨其发病危险因素和防治策略。方法回顾分析1998年10月—2004年6月本移植中心完成的53例儿童HSCT的临床资料,其中脐血移植（UCBT）37例,外周血造血干细胞移植（PBSCT）16例。HC的预防分为2组：（1）常规组（15例）,采用水化、碱化尿液、强力利尿和巯乙磺酸钠（Mesna）;（2）前列腺素E1（PGE1）组（38例）,在常规组的基础上加用PGE1。结果53例中发生HC11例（21％）,其中Ⅰ度2例（2／11,18％）,Ⅱ度4例（4／11,36％）,Ⅲ度5例（5／11,46％）;11例HC中,早发性4例（36％）,迟发性7例（64％）。HC发病时间为＋2d-＋25d（中位时间＋15d,移植后为“＋”）。15例常规预防组中发生HC2例（13％）,38例PGE1组中发生9例（24％,P〉0．05）。单因素分析显示,受者移植年龄≥6岁、预防移植物宿主病（GVHD）阳性、巨细胞病毒（CMV）感染组的HC发生率分别高于年龄〈6岁（32％vs8％,χ^2=4．68,P〈0．05）、GVHD阴性（35％vs7％,χ^2=5．96,P〈0．05）、CMV未感染组（62％vs 13％,χ^2=7．22,P〈0．05）。logistic回归分析表明,HC发病仅与年龄（OR=3．53,P〈0．05）和CMV感染（OR=4．31,P〈0．05）有显著的相关性。采用充分水化、碱化尿液、选择性输注血小板、抗病毒和尿道膀胱冲洗等综合性治疗,全部病例均获得治愈。结论受者移植年龄≥6岁和CMV感染是儿童HSCT并发HC的重要危险因素,PGE1不能降低HC的发生。儿童HSCT后HC预后多良好。     

ͬ��������Ѫ��ϸ����ֲ���ƶ�ͯѪҺ��4������

目的观察同基因外周血造血干细胞移植治疗儿童再生障碍性贫血、白血病的植入情况及疗效。方法北京儿童医院于2004-08—2004-12,对4例分别患有慢性粒细胞性白血病(慢性期)、急性非淋巴细胞白血病(M2)、急性再生障碍性贫血、急性淋巴细胞白血病(ph1+)的患儿进行正规方案治疗,3例白血病患儿获得首次缓解,4例患儿接受不同预处理方案,进行同基因外周血干细胞移植。所有供者均为患儿的同卵双胎同胞,并经重组人粒细胞集落刺激因子(rhG-CSF)动员。结果4例患儿接受干细胞(MNC)平均数量为10·08×108/kg。白细胞及血小板平均植入时间分别为10·7d及12·3d,无明显移植并发症。病例4随诊5个月后复发,放弃治疗2个月后死亡,余病例均存活,可正常生活,随诊时间均在16个月以上。结论同基因外周血干细胞移植可以作为治疗包括白血病在内的多种血液病的有效方法,但其远期效果还有待进一步评估。     

Development of T-cell acute lymphoblastic leukemia in a patient in very long lasting complete remission of juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML) occurs with an incidence of 1.2 per million children a year, and represents 18% to 30% of all myelodysplastic (MDS) and myeloproliferative (MPS) disorders in the age group below 15, being by far the most common MDS/MPS in children younger than 4 years. The only therapeutic approach which results in a definitive cure of patients with JMML is myeloablative chemo-therapy/radio-therapy, followed by allogeneic hematopoietic cell transplantation. Few cases of transformation of JMML in acute lymphoblastic leukemia have been reported. We describe a child with JMML diagnosed at the age of 4 months in whom complete remission was achieved with 13-cis retinoic acid and cytosine-arabinoside and was sustained for 7 years with no maintenance therapy. Ninety-eight months after the diagnosis of JMML was established, overt T-cell leukemia developed. Treatment with acute lymphoblastic leukemia (ALL)-directed chemotherapy induced complete restoration of normal hemopoiesis, but testicular involvement persisted. The patient died after transplantation with unrelated cord blood. This case suggests that JMML is a true stem cell disorder and that stem cell transplantation should be considered, even in patients with a very favorable clinical course.     

Hematologic abnormalities and acute myeloid leukemia in children and adolescents administered intensified chemotherapy for the Ewing sarcoma family of tumors

PURPOSE: Current treatment of the Ewing sarcoma family of tumors (ESFT) includes intensive multiagent chemotherapy with topoisomerase II inhibitors, alkylating agents, and granulocyte colony-stimulating factor (G-CSF). This treatment approach has been associated with myelodysplasia and acute myeloid leukemia. Because macrocytosis and thrombocytopenia are distinctive features of myelodysplasia, the authors evaluated a cohort of patients treated for ESFT to determine the degree and duration of macrocytosis and thrombocytopenia and their relation with the development of therapy-related hematologic malignancies. PATIENTS AND METHODS: The study group consisted of 73 patients with ESFT treated on two consecutive protocols (EW92 and EW87). Both chemotherapy regimens incorporated the same agents but differed in cumulative drug dose, dose per course, and the use of G-CSF. Platelet counts and the mean corpuscular volume (MCV) of erythrocytes were determined at diagnosis and during follow-up visits after completion of treatment. RESULTS: Patients in the EW92 group had significantly greater MCVs after treatment than did the less intensively treated EW87 group. These changes persisted throughout the 40-month observation period. Patients in the EW92 group also had lesser mean platelet counts after treatment than those in the EW87 group. MCV differences (from baseline) were inversely related to platelet counts. The cumulative incidence of treatment-related acute myeloid leukemia was 7.8%+/-4.7% at 4 years in the EW92 group and zero in the EW87 group. CONCLUSION: Patients treated for ESFT with intensive chemotherapy that includes large doses of alkylators, topoisomerase II inhibitors, and G-CSF characteristically have persistently elevated MCVs and decreased platelet counts after completion of therapy. These hematologic abnormalities may represent stem cell damage, predisposing patients to myelodysplasia and acute myeloid leukemia, but further study is needed to establish this relation.     

Long-stay pediatric intensive care unit patients: outcome and resource utilization

Outcome, resource utilization, and health care characteristics of patients staying in a multidisciplinary pediatric intensive care unit (PICU) for more than 13 days (long-stay patients) were analyzed. Of 647 children admitted consecutively, 46 were long-stay patients. Compared with short-stay patients, long-stay patients were significantly younger and sicker and had a higher incidence of chronic disease. Most important, long-stay patients had significantly higher PICU mortality rates (17.4% v 7.3%, P less than .05) and hospital mortality rates (23.9% v 8.7%, P less than .01) than short-stay PICU patients. Although only 7.1% of the patient sample, long-stay patients consumed approximately 50% of all PICU resources. One-year follow-up on those long-stay patients surviving their hospitalization revealed that 58% had died or were severely disabled. Long-stay patients had relatively poor prognoses and consumed health care resources in excess of their numeric proportions.     

Identification of myeloid origin in undifferentiated congenital leukemia by in vitro marrow culture study

A case of congenital leukemia that originally did not express any lineage-specific antigenic markers is presented. The blast cell morphologic appearance was L1 according to French-American-British (FAB) classification and showed lymphoid characteristics by cytochemical staining and transmission electron microscopy. However, immunophenotyping using a variety of monoclonal antibodies did not confirm the lymphoid origin. Furthermore, the immunoglobulin heavy chain and T-cell receptor beta-chain genes were in germ-line configuration. The in vitro culture study defined the leukemia as of myeloid origin. The semisolid methylcellulose culture showed an acute non-lymphocytic leukemia-type growth pattern. Bone marrow blasts underwent myeloid differentiation with positive myeloperoxidase and butyrate esterase activity during a suspension culture. These findings indicate that this case represents an acute undifferentiated leukemia that has probably arisen from the malignant transformation of stem cells of myeloid progeny.