Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group Study.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) who experience hematologic recurrence while receiving chemotherapy or within 6 months after its cessation have a low cure rate. In this study (Pediatric Oncology Group Protocol 8303) two methods were examined for improving the outcome in these children. METHODS: After remission induction with prednisone, vincristine, daunorubicin, and asparaginase (PVDA) and consolidation chemotherapy with teniposide and cytarabine, patients received weekly continuation chemotherapy with rotating pairs of drugs, comprised of teniposide and cytarabine and vincristine and cyclophosphamide. In addition, they were randomized to receive or not receive repeated reinduction with PVDA. Patients with matched sibling donors were allowed to receive allogeneic bone marrow transplantation (BMT) instead of continued chemotherapy. RESULTS: Of 297 evaluable patients 258 (87%) achieved second complete hematologic remission. However, only 23 of these patients remained continuously free of leukemia > or =7 years after chemotherapy or BMT. Neither PVDA pulses nor BMT appeared to influence outcome at a statistically significant level. CONCLUSIONS: The results of the current study confirm prior reports of the low cure rate of children with ALL who experience hematologic recurrence during initial therapy or shortly after its cessation. New approaches are needed to prevent and retreat hematologic recurrence in pediatric ALL patients.

In vitro and in vivo persistence of reticulocytes from donor red cells.

BACKGROUND: Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit. STUDY DESIGN AND METHODS: Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37 degrees C by using thiazole orange staining and flow cytometric analysis. Two-color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients. RESULTS: Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA-1 blood was temperature-dependent. Reticulocytes disappeared over 13 and 6 days at 24 degrees C and 37 degrees C, respectively, but at 4 degrees C the reticulocyte count changed little over 35 days. Two-color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients. CONCLUSION: This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.

Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis.

We reviewed our experience with paired quantitative and standard blood cultures in the evaluation of children with suspected central-line sepsis with the hypothesis that by employing both systems we would increase our yield of pathogenic isolates. A total of 913 paired cultures were reviewed, representing 267 pathogenic isolates and 58 individual episodes of sepsis. The isolates were analyzed for recovery rates for each system and by combining both systems. The Isolator system proved to be equal to the BACTEC system for the recovery of all groups of pathogenic isolates. The combined use of both the quantitative and the standard culture systems demonstrated a statistically significant advantage (p less than 0.001) for the recovery of pathogens as compared with either system alone. The use of either system alone would have missed 15% of the total pathogenic isolates. Quantitative colony counts were helpful in identifying the line as the source of infection in 35 to 58 episodes of sepsis and were often beneficial in the clinical management central venous line infection. We recommend the use of the Isolator 1.5 ml combined with a conventional broth-bottle system in selected pediatric patients to enhance the recovery of pathogenic organisms.

Antimicrobial therapy of Broviac catheter infections in pediatric hematology oncology patients.

Long-term therapy of pediatric oncology patients has been facilitated by permanent indwelling venous catheters. Over a 3-year period, 54 Broviac catheters were placed in 43 oncology patients and two hemophiliacs. There were 20 episodes of sepsis in 14 patients and the most common bacteria were S epidermidis (4), S aureus (4), and K pneumoniae (3). Catheter exit site infections occurred ten times in six patients; S aureus eight of ten. Antibiotic therapy without catheter removal was successful in 18 of 20 children with catheter sepsis and 8 of 10 patients with exit site infections. These data strongly suggest that although catheter-related infections are common, removal of Broviac catheters is not required for successful treatment of the infection.

A group B streptococcal extract reduces neutrophil counts and induces neutrophil aggregation.

The possibility that group B streptococci (GBS) may induce neonatal neutropenia by promoting neutrophil aggregation and the entrapment of aggregates in the lung was studied in vivo and in vitro utilizing a cell free GBS extract [(GBS)-trichloroacetic acid (TCA)]. The intravenous infusion of the extract into neonatal lambs induced reductions of circulating white blood cells (0 time, 3.1 X 10(3)/mm3 +/- 0.5 versus 2.2 X 10(3)/mm3 +/- 0.7) 5 min after infusion (p less than 0.01). At necropsy these lambs had prominent accumulation of polymorphonuclear leukocytes in their pulmonary interstitium. Subsequently, neutrophil aggregation was studied by incubating GBS-TCA in human serum or phosphate-buffered saline with subsequent addition to human polymorphonuclear leukocytes in an aggregometer. GBS-TCA incubated in human serum induced prompt polymorphonuclear leukocyte aggregation (mean delta T 12.3% +/- 2.8 in human serum versus delta T 2.5% +/- 2.1 in phosphate-buffered saline, p less than 0.001). Preincubation of GBS-TCA followed by incubation in human serum with human GBS hyperimmune IgG significantly reduced aggregation (GBS-TCA in serum mean delta T 14.9 +/- 2.44 versus 5.42 +/- 1.80, p = 0.002). Cell-free GBS products may induce polymorphonuclear leukocyte aggregation in the presence of whole serum. This phenomenon might contribute to the pulmonary injury experienced by infants with GBS pneumonia and sepsis.

Granulocyte transfusion therapy in children.

A prospective study of 45 granulocyte transfusions in children using continuous flow centrifugation is reported. During 13 episodes of proven or presumed infection, only two children failed to show a favorable response to granulocyte transfusion. The neutropenic child shows a significantly increased absolute granulocyte count one hour after transfusion. The granulocyte counts at one hour after transfusion are inversely proportional to the child's size. A child with chronic granulomatous disease who had documented Nocardia asteroides sepsis and pneumonia exhibited complete recovery following granulocyte transfusion. Dramatic responses to the nonrandom use of granulocyte transfusion have been observed in children with major gram-negative bacterial infections. Endorsement of granulocyte transfusion for instances of presumed, but unproven, infection in the neutropenic child will require randomization to control the variables of antibiotic therapy and bone marrow remission.