Variation in administration of cyclophosphamide and mesna in the treatment of childhood malignancies.

The objective of this study was to describe the variation in preparation and administration of cyclophosphamide, mesna, and hydration for the treatment of childhood malignancies within clinical trial protocol documents. All cyclophosphamide-containing cooperative group (Pediatric Oncology Group) protocols that were open at Dana-Farber Cancer Institute in April 1998 were evaluated. Among the 14 active protocols, there were 23 unique cyclophosphamide regimens. Marked variation existed in infusion rate, fluid type, and volume used for admixing cyclophosphamide and mesna, as defined in the "Treatment" section of the protocols that we evaluated. Further variation was found in the type, amount, and rate of infusion of prehydration and posthydration fluid. Internal inconsistency existed within the protocols pertaining to the administration methods described in the "Agent Information," "Treatment," and "Consent" sections of the written documents. Clinical trial protocol documents serve as reference material for health care providers who prescribe, dispense, and administer protocol chemotherapy. Misinterpretation of protocol documents and clinician orders are contributing factors in serious and deadly medication errors. Internal inconsistency within protocol documents and variation in drug administration across protocols is a potential source of error. We recommend improved accuracy, clarity, and internal consistency of protocol documents to improve patient safety and compliance with protocol specifications. In addition, the use of standard concentrations, volumes, and methods of administration of chemotherapeutic agents and accompanying fluids is recommended.

Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation.

Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines. Following transplantation, patients received HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12, and 24 months and 23-valent pneumococcal vaccine at 12 and 24 months. Thirty-three patients with unimmunized donors were immunized following transplantation in an identical manner. Patients whose donors were immunized had significantly higher total anti-HIB antibody concentrations at 3 months (P = .0001), 6 months (P = .0001), 12 months (P = .0001), and 24 months (P = .002) after transplant compared with patients whose donors were unimmunized. Higher antitetanus toxoid antibody concentrations were also noted in patients with immunized donors, whereas donor immunization with pneumococcal vaccine had no effect on antibody concentrations following transplantation. Donor immunization with HIB-conjugate vaccine resulted in higher antibody concentrations in patients as early as 3 months after allogeneic transplantation and may be an effective strategy to prevent HIB infections.

Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters.

Multiple bone marrow aspirations or biopsies and lumbar punctures are a necessary part of the diagnosis and treatment of many pediatric cancer patients. Pharmacologic sedation may decrease the distress associated with these procedures. Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children. We prospectively evaluated safety and recovery parameters for intravenous MDZ used for conscious sedation by oncologists (without an anesthesiologist in attendance) for 70 procedures (bone marrow aspirations, lumbar punctures, or bone marrow aspirations plus lumbar punctures) in 24 ambulatory pediatric cancer patients, aged 1.5 to 15.5 years. MDZ was used alone or in combination with morphine or fentanyl. Respiratory rate, oxygen saturation, blood pressure, and heart rate were monitored. Sedation, anxiolysis, and recovery were assessed with a behavior score and a modified recovery room discharge score. Restraint was not required in 45% of the procedures. In no case was a respiratory rate less than 12 observed. In nine procedures (13%), an oxygen saturation less than or equal to 90 occurred, all within 10 minutes after the last dose of MDZ. Ten procedures (14%) required verbal stimulation to take deeper breaths. Two patients did not respond immediately to verbal stimulation and received face-mask oxygen. Hypoxemia was not correlated with opioid use. Hypoxemia appears to be related to total MDZ dose and may occur with normal respiratory rates; all cases resolved with verbal stimulation or face-mask oxygen without specific airway maneuvers or assisted ventilation. Heart rate and blood pressure remained stable in all 70 procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of trimethoprim-sulfamethoxazole to prevent bacterial infections in children with acute lymphoblastic leukemia.

We assessed the efficacy of prophylactic antibiotics in children receiving intensive chemotherapy for acute lymphoblastic leukemia. The patients were randomized to receive either trimethoprim-sulfamethoxazole (TMP-SMX) or placebo in a double-blind trial. Thirty patients were evaluated in each group. Children receiving TMP-SMX had fewer episodes of bacteremia (0 vs. 5) and otitis media (3 vs. 18). The geometric mean of the neutrophil nadir was 172 in the TMP-SMX group and 287 in controls. However, no increased delay or dose reduction of chemotherapy was observed in the TMP-SMX treated patients. Five patients who received TMP-SMX developed Gram-negative rods resistant to TMP-SMX on surveillance stool cultures. We conclude that TMP-SMX prophylaxis decreased certain bacterial infections in children with acute lymphoblastic leukemia without causing clinically significant toxicity. The emergence of Gram-negative rods resistant to TMP-SMX in treated patients suggests that TMP-SMX prophylaxis should be restricted to patients who are at high risk for developing a bacterial infection or Pneumocystis carinii pneumonia.