Therapists' and patients' experiences of using patients' self-reported data in ongoing psychotherapy processes-A systematic review and meta-analysis of qualitative studies.

OBJECTIVE: Using patient-generated quantitative data in psychotherapy (feedback) appears to enhance treatment outcome, but there is variability in its effect. Different ways and reasons to implement routine outcome measurement might explain such variability. The goal of this review is to address the insufficient knowledge on how these data are used by therapists and patients. METHODS: The present study is a systematic review and meta-analysis of qualitative reports of therapists' and patients' experiences using patient-generated quantitative data during ongoing psychotherapy. RESULTS: Four main categories of use were identified: (1) uses of patients' self-reported data as nomothetic/objective markers for assessment, process monitoring, and treatment planning; (2) intrapersonal uses that enhance self-awareness, initiate reflection, and influence patients' mood or responses; (3) uses that prompt interactional processes by facilitating communication, supporting exploration, creating ownership in patients, changing treatment focus, enhancing therapeutic alliance, or disturbing the psychotherapy process; and (4) patients responding for specific purposes due to uncertainty and interpersonal motives, or strategic responding to achieve a desired result. CONCLUSION: These results demonstrate that patient-reported data, when used in active psychotherapy, is very clearly not just an objective measurement of client functioning: the inclusion of patient-data has the potential to influence psychotherapy in numerous ways.

Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report.

BACKGROUND: The outcome of children with relapsed Wilms' tumor is poor, especially with poor-risk factors such as unfavorable histology, early recurrence, previous three-drug therapy, relapse not confined to lungs and abdominal relapse following abdominal radiotherapy. We report the overall response rate, progression-free survival and overall survival of 11 children with relapsed and poor-risk Wilms' tumor following ifosfamide/carboplatin/etoposide (ICE) chemotherapy. PATIENTS AND METHODS: ICE therapy consisted of ifosfamide 1800 mg/m2/day (on day 0-4), carboplatin 400 mg/m2/day (on day 0-1) and etoposide 100 mg/m2/day (on day 0-4). The median age at diagnosis was 39 months (range from 13 months to 16 years) and the median time to relapse after initial diagnosis was 9 months (range 4-72 months). All but one patient had at least one poor prognostic feature, with eight patients showing three or four. RESULTS: After ICE chemotherapy the number of patients showing a complete response (CR) was three (27%) and a partial response (PR) was six (55%). The overall response rate (CR+PR) was 82%. Five of the six patients with a PR subsequently achieved a CR with further therapy. The 3-year event-free survival and overall survival were 63.6 +/- 14.5%. CONCLUSIONS: The response rate in children with relapsed and poor-risk Wilms' tumor is >80% with ICE re-induction chemotherapy followed by post-ICE therapy. The optimal approach for post-ICE consolidation therapy has yet to be determined.

Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non Hodgkin's lymphoma: a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) adopted a histology-based approach to the management of pediatric non-Hodgkin's lymphomas (NHL) utilizing the National Cancer Institute Working Formulation for Clinical Usage. Patients with diffuse large cell lymphoma (DLCL) were treated on a separate protocol from small cell diffuse undifferentiated or lymphoblastic lymphomas. This study assessed the overall and event free survival of children with DLCL and determined the effects of cyclophosphamide upon these end-points in a prospective randomized trial. One hundred and twenty eligible stage III or IV NHL patients with the confirmed diagnosis of diffuse large cell or immunoblastic histology were enrolled on study between October 1986 and November 1991. Patients were randomized to receive or not receive cyclophosphamide; 58 received cyclophosphamide, doxorubicin, vincristine, 6-mercaptopurine (6-MP), and prednisone (ACOP+) and 62 were treated with doxorubicin, vincristine, 6-MP, and prednisone (APO). In both treatment programs methotrexate was substituted when the doxorubicin cumulative dose reached 450 mg/m2. Radiation was administered to bulky disease if progression or no response were observed after induction therapy. Planned duration of therapy was 12 months. The 5-year event free survival (EFS) rates of patients treated with ACOP+ versus APO were 62% +/- 7% and 72% +/- 6%, respectively. While there was no statistically significant difference between the two treatment arms (p = 0.28), we can only say that we are 95% confident that the difference in 5-year EFS falls in the wide range from 28% in favor of APO to 8% favoring ACOP+. Marrow suppression was the main toxicity with one fatal infection. There were three other deaths on study due to respiratory failure in patients with mediastinal masses. Only one patient experienced cardiotoxicity requiring discontinuation of doxorubicin. Ten patients received radiation therapy to achieve. In conclusion the efficacy of elimination of cyclophosphamide from the treatment program of children and adolescents with advanced stage diffuse large cell lymphoma was inconclusive as to its effect on EFS. Furthermore, the majority of the patients (92%) did not require any radiation therapy to bulky disease indicating that the chemotherapy regimens are quite efficient for achievement of complete remission.

CD34 expression by murine hematopoietic stem cells. Developmental changes and kinetic alterations.

For more than a decade it was believed that hematopoietic stem cells express CD34. However, this dogma was recently challenged by the observation that stem cells of normal adult mice are CD34-. In order to clarify the controversy, we carried out systematic examination of stem cells by using C57BL/6 mice that are congenic for Ly-5. As reported previously, stem cells in the normal adult mice were CD34-. However, stem cells stimulated in vivo by 5-fluorouracil injection or in vitro by a combination of interleukin-11 and steel factor were CD34+. The activated CD34+ stem cells reverted to CD34- when the recipients' marrow achieved steady state. The majority of G-CSF-mobilized stem cells also were CD34+ and reverted to CD34- under steady-state conditions. Most recently, we examined the developmental changes of stem cell CD34 expression. In order to gain information on the total population of stem cells we prepared CD34+ and CD34- populations of mononuclear cells without prior enrichment and studied their engrafting potentials. All stem cells from perinatal to 5-week-old mice were CD34+. In 7-week-old mice CD34- stem cells began to emerge, and the majority of the stem cells were CD34- in the 10- and 20-week-old mice. An estimated 20% of the adult stem cells expressed CD34. These observations provide insight into the current controversy regarding CD34 expression by adult hematopoietic stem cells.

Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells.

The effects of activation of adult murine stem cells on their expression of CD38 were studied using a murine transplantation model. First, the published finding that the majority of long-term engrafting cells from normal adult steady-state marrow are CD38(+) was confirmed. Next, it was determined that the majority of stem cells activated in vivo by injection of 5-fluorouracil (5-FU) or mobilized by granulocyte colony-stimulating factor are CD38(-). Stem cells that were activated in culture with interleukin-11 and steel factor were also CD38(-). Previous studies have shown that expression of CD34 by adult stem cells is also modulated by in vivo or in vitro activation. To determine whether there is reciprocal expression of CD38 and CD34, 4 populations of post-5-FU marrow cells were analyzed. The majority of the stem cells were in the CD38(-)CD34(+) fraction. However, secondary transplantation experiments indicated that when the bone marrow reaches steady state, the majority of the stem cells become CD38(+)CD34(-). In addition, the minority populations of CD34(+) stem cells that occur in steady-state bone marrow are CD38(-). This reversible and reciprocal expression of CD38 and CD34 by murine stem cells may have implications for the phenotypes of human stem cells.

Assessment of barriers to bone marrow donation by unrelated African-American potential donors.

African Americans have a lower registration rate for becoming potential bone marrow and stem cell donors. The same attitudes and behaviors are exhibited in regard to solid organ and blood donations, causing a serious under-representation of the African-American population in the donor pool. In our efforts to increase donor availability for African Americans through a project funded by the Medical University of South Carolina, we used a survey to determine the reasons African Americans do not participate as donors for bone marrow. We surveyed 589 African Americans, a great majority of whom were women. Our survey identified major barriers to donation to be the lack of awareness that transplantation can save lives, the cost of donation, and the lack of opportunities to donate. The most effective interventions in increasing donation have been to provide both educational programs preceding marrow drives and the opportunity to donate. Through these efforts, the number of potential African-American donors has increased from 768 (accrued over a period of 12 years) to 1977 in less than 2 years. We conclude that a minority recruitment program targeting African-American volunteers for the National Marrow Donor Program (NMDP) should include an education component addressing the most common barriers before drives.

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease.

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

CD34 expression by murine hematopoietic stem cells mobilized by granulocyte colony-stimulating factor.

Controversy has existed about CD34 expression by hematopoietic stem cells. We recently reported that CD34 expression reflects the activation state of stem cells by using a murine transplantation model. It has been generally held that mobilized blood stem cells express CD34.However, it has also been reported that mobilized stem cells and progenitors are in G0/G1 phases of the cell cycle. To address the state of CD34 expression by the mobilized stem cells, we again used the mouse transplantation model. We prepared CD34(-) and CD34(+) populations of nucleated blood cells from granulocyte colony-stimulating factor-treated Ly-5.1 mice and assayed each population for long-term engrafting cells in lethally irradiated Ly-5.2 mice. The majority of the stem cells were in the CD34(+) population. The CD34 expression by mobilized stem cells was reversible because re-transplantation of Ly-5.1 CD34(-) marrow cells harvested from the Ly-5.2 recipients of CD34(+)-mobilized stem cells 8 months posttransplantation revealed long-term engraftment. These results may support the use of total CD34(+) cells in mobilized blood as a predictor for engraftment and CD34 selection for enrichment of human stem cells. (Blood. 2000;96:1989-1993)

Growth factor practice patterns among pediatric oncologists: results of a 1998 Pediatric Oncology Group Survey. Economic Evaluation Working Group the Pediatric Oncology Group.

The American Society of Clinical Oncology (ASCO) guidelines on growth factor (GF) use recommend applying adult-derived guidelines in pediatric oncology. An ASCO survey of adult oncology GF use determined the preference for first degree prophylaxis (use of GF when febrile neutropenia [FN] is expected to be high in untreated patients), second-degree prophylaxis (administration of GF after a documented episode of FN on a previous cycle of chemotherapy), and intervention in the treatment of FN. Similar preferences have not been evaluated in pediatrics. The purpose of this study was to (1) characterize GF use in pediatric oncology; (2) correlate use patterns with demographic factors; and (3) compare the Pediatric Oncology Group (POG) and ASCO surveys. The ASCO survey was revised for use within pediatric oncology and was mailed to the physician membership of POG; 341 were returned (86% completion rate). Comparisons were made with the ASCO survey. Most (76%) physicians said GF use was determined by protocol requirements and most (70%) patients were entered on POG protocols. GF use as first-degree prophylaxis was selected 40% of the time, which was significantly greater than in adults; this was most influenced by anticipated duration of neutropenia (> or =7 days). The severity of the initial clinical course (e.g., neutropenia, infection) influenced use in second-degree prophylaxis; dose reduction alone was never selected. For FN, GF use was 45%, with lower preferences in uncomplicated FN (16%-38%) compared with complicated FN (66%). POG respondents endorse greater use of GF for first-and second-degree prophylaxis but less use in uncomplicated FN than do ASCO respondents. These patterns may reflect different strategies, including the role of chemotherapy, value of dose intensity, and perceived toxicity of regimens. Given these differences, adult-based guidelines may not be appropriate for pediatrics.

Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.

INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.

Cost analyses of adjunct colony stimulating factors for acute leukemia: can they improve clinical decision making.

Colony stimulating factors reduce the duration of neutropenia following intensive chemotherapy in a variety of settings, but the advantages in the management of leukemia are inconclusive. The variations in clinical results and the high costs of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) have led to confusion over appropriate use for leukemia patients. In this paper, we reviewed published information on costs and cost-effectiveness of growth factors for childhood and adult leukemia patients. Medline and Healthstar databases were searched for original research articles that contain cost or cost-effectiveness analyses of G-CSF (filgrastim) and GM-SCF (sargramostim) in oncology cooperative group trials. Published manuscripts and abstracts presented at national or international oncology conferences were included. The cost of adjunct treatment was evaluated in two studies of pediatric ALL, one study of adult AML, and two studies of AML in older adults (>55 years). The use of G-CSF for children with ALL was associated with reductions in days to ANC recovery, fewer documented infections, a shorter duration of hospitalization, and small (but not significant) additional costs. In adult AML patients, benefits included a shortening of the duration of neutropenia and hospital stays, a lower incidence of infection and febrile episodes, less use of antibiotics, and cost savings of $2,230 and $2,310 in two studies and an increase if $120 in the third study. This summary suggests that economic analyses can provide useful information to assist clinical decision-making. For pediatric ALL patients, this information indicates that G-CSF use is unlikely to have significant cost implications, and its use should be based on clinical considerations. In studies of adult and older adult AML patients, both GM-CSF and G-CSF have clinical benefits and can be expected to lead to a decrease in overall costs.

Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report.

Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) postinduction. Modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC >50000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186000/mm3 and 200000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs. non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs. the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs. 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: a case for prospective economic analysis in cooperative group trials.

BACKGROUND: Growth factor use has been shown to ameliorate chemotherapy-induced neutropenia, leading to shorter hospital stays and lower use of parenteral antibiotics, two costly areas of cancer treatment. Prior reports on pediatric patients have shown evidence of cost savings in some studies, but no such evidence in others. In this study a retrospective analysis compared the costs of inpatient supportive care for pediatric patients with T-cell leukemia and advanced lymphoblastic lymphoma enrolled in a Pediatric Oncology Group trial. PROCEDURE: Patients 1-22 years of age were randomized to receive either granulocyte colony-stimulating factor (G-CSF; n = 45) or no G-CSF (n = 43) following induction and two cycles of maintenance therapy. There were no significant differences in neutropenia-related outcomes during the induction phase. During maintenance therapy, G-CSF patients had significantly fewer days to an ANC >500 cells/microl and a trend towards fewer days of hospitalization. Data on resource utilization were tabulated from case report forms. Costs were imputed from national data on hospitalization costs, average wholesale prices of pharmaceuticals, and patient billing information from a single institution. RESULTS: Total median costs of supportive care were $34,190 for patients receiving G-CSF and $28,653 for patients not receiving G-CSF (P > 0. 05 for the cost difference). Sensitivity analyses demonstrated that the total cost difference was not statistically significant, even in scenarios that included reasonable variations in estimates of the range of the length of stay, antibiotic regimen, and dosage and cost of G-CSF. CONCLUSIONS: In the setting of pediatric leukemia, the cost of growth factor may offset potential savings from shorter hospital stays or lower antibiotic use, a finding consistent with that from the Children's Cancer Study Group.

Interleukin 8 in middle ear fluid during acute otitis media: correlation with aetiology and bacterial eradication.

OBJECTIVES: To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation. STUDY DESIGN: Middle ear fluid was obtained by tympanocentesis at enrollment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay. RESULTS: 101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40 paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12,636 (23,317) v 5,920 (7,080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15,420 (15,418) v 6,695 (5,092) pg/ml). CONCLUSIONS: Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

Reversible expression of CD34 by murine hematopoietic stem cells.

We used a mouse transplantation model to address the recent controversy about CD34 expression by hematopoietic stem cells. Cells from Ly-5.1 C57BL/6 mice were used as donor cells and Ly-5.2 mice were the recipients. The test cells were transplanted together with compromised marrow cells of Ly-5.2 mice. First, we confirmed that the majority of the stem cells with long-term engraftment capabilities of normal adult mice are CD34(-). We then observed that, after the injection of 150 mg/kg 5-fluorouracil (5-FU), stem cells may be found in both CD34(-) and CD34(+) cell populations. These results indicated that activated stem cells express CD34. We tested this hypothesis also by using in vitro expansion with interleukin-11 and steel factor of lineage(-) c-kit(+) Sca-1(+) CD34(-) bone marrow cells of normal mice. When the cells expanded for 1 week were separated into CD34(-) and CD34(+) cell populations and tested for their engraftment capabilities, only CD34(+) cells were capable of 2 to 5 months of engraftment. Finally, we tested reversion of CD34(+) stem cells to CD34(-) state. We transplanted Ly-5.1 CD34(+) post-5-FU marrow cells into Ly-5.2 primary recipients and, after the marrow achieved steady state, tested the Ly-5.1 cells of the primary recipients for their engraftment capabilities in Ly-5.2 secondary recipients. The majority of the Ly-5.1 stem cells with long-term engraftment capability were in the CD34(-) cell fraction, indicating the reversion of CD34(+) to CD34(-) stem cells. These observations clearly demonstrated that CD34 expression reflects the activation state of hematopoietic stem cells and that this is reversible.

Dynamics of interleukin-1 production in middle ear fluid during acute otitis media treated with antibiotics.

In an ongoing prospective study, IL-1 concentrations were measured in 78 children (aged 3-36 months) with acute otitis media receiving antibiotics. Middle ear fluid IL-1 concentrations were determined using ELISA kits. Ninety-eight middle ear fluid samples were obtained by tympanocentesis at enrollment (day 1) and 43 samples were collected on days 4-5. Ninety-two pathogens were isolated in 77/98 samples obtained on day 1: 55 Haemophilus influenzae, 34 Streptococcus pneumoniae, 2 Moraxella catarrhalis and 1 Streptococcus pyogenes. Among 37 paired samples initially culture-positive, eradication of the pathogen was achieved on day 4-5 in 20 while pathogens were still present in 17. On day 1, IL-1 was detected in 61/77 (79%) culture-positive samples vs 9/21 (43%) culture-negative ones (P = 0.003). The mean +/- SD middle ear fluid concentration of IL-1 on day 1 was significantly higher in culture-positive (316 +/- 508 pg/ml) than in culture-negative samples (111 +/- 245 pg/ml) (P = 0.01). When paired samples were evaluated, IL-1 decreased on days 4-5 in 13/20 (65%) ears where bacterial eradication was achieved, but also in 11/19 (58%) with persistent or new infection. The mean IL-1 concentrations decreased on days 4-5 in the 20 samples from ears where bacterial eradication was achieved (330 +/- 460 vs 118 +/- 294 pg/ml, P = 0.1) but also in the 17 samples where it was not (465 +/- 660 vs 232 +/- 289 pg/ml, P = 0.02). No significant differences were found between day 1 and days 4-5 in the mean IL-1 concentrations measured in patients with H. influenzae vs S. pneumoniae or concomitant H. influenzae and S. pneumoniae. It was concluded that: 1) IL-1 was detected in the middle ear fluid of most patients with acute otitis media; 2) significantly higher IL-1 concentrations were found in patients with culture-positive than in those with culture-negative acute otits media; 3) IL-1 concentrations decreased on days 4-5 of antibiotic therapy, whether the pathogen was eradicated or not.

NK cell colony formation from human fetal thymocytes.

We established a clonal cell culture system for human natural killer (NK) cells from fetal thymocytes. Thymocytes of 16 to 22 gestational weeks were cultured in methylcellulose in the presence of interleukin (IL)-7, IL-15, and steel factor (SF). After 14 days in incubation, large, diffuse colonies consisting of small cells were identified. Cells in the colonies were medium- to large-sized granular lymphocytes, expressing CD56 but not CD3, and revealed lytic activity against K562 cells. Colony-forming units (CFU)-NK were enriched in lineage negative (Lin- ) CD34++ subpopulations of fetal thymocytes, whereas a smaller number of CFU-NK also existed in Lin-CD34+ and Lin-CD34- subpopulations. Cytokine requirement for the NK cell colony formation was examined under serum-free conditions. As a single agent, only IL-15, but not IL-2, IL-7, or SF, supported NK cell colony formation. IL-15 had synergy with IL-7 and SF independently, and the maximal number of colonies were obtained when the three cytokines were present. IL-2 also supported NK cell colony formation in the presence of SF. When IL-2 was added to cultures containing IL-15 alone, IL-15 plus SF, or IL-15, SF, and IL-7, the numbers of NK cell colonies were reduced relative to those without IL-2. These results indicate that IL-2 may regulate IL-15-responsive NK cell progenitors. This clonal culture system will be a useful tool in the investigation of NK cell ontogeny.

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study.

This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.

OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, /=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

Postdural puncture headache in paediatric oncology patients.

PURPOSE: Previous studies have not determined the correlation between dural puncture and postural headache in paediatric patients. Furthermore, no studies have evaluated the correlation between atypical headache and dural puncture in the paediatric population. Therefore, we prospectively analyzed the incidence of typical postdural puncture headache (PDPHA) and atypical headache in paediatric oncology patients following dural puncture. METHODS: The study population consisted of 66 paediatric patients undergoing 128 consecutive procedures, including 99 lumbar punctures and 29 bone marrow aspirations without concomitant lumbar puncture. Patients were prospectively randomized into four groups: Group I, preteens (< 13 yr) undergoing lumbar puncture, Group II, adolescents (13-21 yr) undergoing lumbar puncture, Group III, preteens undergoing bone marrow aspiration, and Group IV, adolescents undergoing bone marrow aspiration. The presence and description of headache was documented immediately after dural puncture or bone marrow aspiration, and on post-procedure days # 1, 3 and 5 by personnel blinded to the type of procedure. RESULTS: There was an increase in the incidence of headache (9.1%) after lumbar puncture in patients < 21 yr relative to patients undergoing bone marrow aspiration (P < 0.05). No difference was found between the incidence of typical PDPHA after dural puncture in preteens and adolescents. There was also no difference in the incidence of atypical headache after dural puncture or after bone marrow aspiration among preteens and adolescents. CONCLUSIONS: Paediatric patients experience an increased incidence of typical postdural puncture headache after dural puncture compared with age-matched patients undergoing bone marrow aspiration only. Atypical headache is relatively common in the paediatric population after dural puncture or bone marrow aspiration.