Richard J. Creger

Lowering the Prophylactic Platelet Transfusion Threshold: a Prospective Analysis

The 20 × 109/L threshold for prophylactic platelet transfusion may be unnecessarily high. Few prospective studies, however, in which other trigger values were tested have been published. In this study all hospitalized, thrombocytopenic adult hematology-oncology patients in our institution were prospectively evaluated daily for hemorrhage and platelet transfusion during a one year period; no patients were excluded for bleeding or infectious problems. By design, during the initial six-months (baseline period), the prophylactic platelet transfusion trigger was 20 × 109/L; for the second six-months (study period) this threshold was changed to 10 × 109/L. Patients studied during the two periods did not differ significantly in age, gender, diagnosis, blood or marrow transplant status, and duration of neutropenia. Compliance with the thresholds was 95.6% (baseline period) and 93.5% (study period). For patients with platelet counts under 20 × 109/L, the mean use of platelet transfusions per patient per day was significantly lower in the study period (4.47) than in the baseline period (6.48; p < 0.001). Both mean prophylactic (1.54/patient-day) and therapeutic (2.93/patient-day) platelet transfusions were reduced in the study period compared with the baseline period (2.26 and 4.22/patient-day, respectively). Hemorrhage was slightly reduced in the study period compared with the baseline period: major hemorrhage, 15.2% vs. 18.4% (p = 0.014); minor hemorrhage, 63.6% vs. 70.1% (p < 0.001). Thus, hemorrhage was not increased with the lower trigger level. A 10 × 109/L prophylactic platelet transfusion threshold value is safe and effective.

Transfer of the hematopoietic stem cell transplant patient to the intensive care unit: does it really matter?

We critically reviewed published English language literature and concluded that from 1998 onward the survival of hematopoietic stem cell transplant (SCT) patients who experienced intensive care unit (ICU) transfer has improved. The factors associated with increased mortality during ICU stay included increased patient age, allogeneic transplant, intubation/mechanical ventilation, multiorgan system failure (MOSF), presumed/documented infection, graft-versus-host disease, and higher APACHE and O-PRISM score at ICU transfer. This encouraging outcome trend reflects evolving advances such as use of recombinant hematopoietic growth factors, use of mobilized blood cells rather than marrow, protective strategies for acute lung injury and early goal-directed therapy for sepsis syndrome. Patient selection bias (which patients were transferred and which were not sent to an ICU) also plays a role in ICU survival rates. New strategies to improve upon SCT patient outcome include use of a scoring system to predict mortality, better therapies for MOSF and integration of ICU components and multispecialist involvement earlier in the clinical course to prevent severe complications such as respiratory failure. SCT recipients comprise a heterogeneous group; to further advance this field, prospective multicenter trials involving larger populations from many centers are needed to reduce the biases of retrospective and single-center reports.

Role of Upper Endoscopy in Evaluation of Upper Gastrointestinal Symptoms in Patients Undergoing Bone Marrow Transplantation

We reviewed our upper endoscopy (esophagogastroduodenoscopy, EGD) experience in a group of 65 consecutive patients receiving carmustine (BCNU) 600 mg/m2, cisplatin 200 mg/m2, VP-16 2400 mg/m2, and autologous bone marrow transplantation (BMT) for relapsed or refractory non-Hodgkins lymphoma or Hodgkins disease. Forty-one patients (33 with chest irradiation) underwent 48 EGDs for the following symptoms: upper gastrointestinal bleeding (melena and/or hematemesis) (12/48); persistent nausea and vomiting (7/48); odynophagia (25/48); and dysphagia (14/48). All patients who had dysphagia or odynophagia had endoscopic evidence of severe esophagitis, with confluent erosions or ulcerations. Gastrointestinal bleeding, which presented as melena or hematemesis, was caused by severe esophagitis in 11 of 12 patients. Yeasts were detected in 11/42 histological, or cytological specimens and were isolated in 4/26 cultures. No bleeding or infectious complications occurred in any patient as a result of the EGD procedure. We conclude that severe esophagitis documented by EGD is common in lymphoma patients receiving autologous BMT. Use of EGD, however, did not affect the decision to initiate empirical therapy with amphotericin B for persistent fever.

Fluctuation of serum phenytoin concentrations during autologous bone marrow transplant for primary central nervous system tumors.

SummaryWe reviewed our experience for adult patients receiving oral anticonvulsant therapy during high-dose chemotherapy and autologous bone marrow re-infusion for primary malignant tumors of the central nervous system. Nineteen patients received either iv carmustine (BCNU) 900–1050 mg/m2 and 6120 cGy cranial irradiation (N = 10), iv carmustine 900–1050 mg/m2 and iv cisplatin 200 mg/m2 (N = 8), or iv carmustine 600 mg/m2, iv cisplatin 200 mg/m2, and iv etoposide 2400 mg/m2 (N = 1). Anticonvulsant therapy consisted of phenytoin alone (N = 8), phenobarbital alone (N = 4), carbamazepine alone (N = 2), phenytoin and carbamazepine (N = 2), carbamazepine and phenobarbital (N = 1), and no anticonvulsant therapy (N = 2). Serum anticonvulsant concentrations were monitored frequently and doses adjusted to keep values in the therapeutic range. While phenobarbital and carbamazepine doses remained relatively stable, all patients required increased doses of phenytoin anticonvulsant therapy after beginning chemotherapy (mean onset 3.7 days after initiation of chemotherapy). The increase in phenytoin dose ranged from 50% to 300% above baseline (mean 134%). By the time of discharge from the hospital (approximately 3–4 weeks after the start of chemotherapy) anticonvulsant dose was decreased to near pre-therapy levels. These swings coincided with the initiation of dexamethasone therapy for antiemetic effect and were more pronounced in patients also receiving cisplatin therapy. Due to close monitoring of serum phenytoin concentrations, no instances of toxicity due to excessive drug concentration, or seizures due to subtherapeutic doses, were noted in patients with primary CNS malignancies. Serum phenytoin concentrations fluctuate markedly during high-dose chemotherapy and must be analyzed frequently during the course of therapy.

Renal dysfunction during high-dose cisplatin therapy and autologous hematopoietic stem cell transplantation: Effect of aminoglycoside therapy

PURPOSEnRenal dysfunction is a common cause of morbidity after cancer therapy and bone marrow transplantation. In this study, we evaluated the effects of aminoglycosides and other nephrotoxic antibiotics on the occurrence of renal dysfunction in patients who received high-dose cisplatin-containing chemotherapy regimens.nnnPATIENTS AND METHODSnThe subjects of this analysis were 102 consecutive patients, studied from September 1985 to February 1991, who received high-dose cisplatin, administered as 40 mg/m2 for 5 consecutive days in 3% saline with saline hydration and mannitol diuresis, followed by autologous stem cell transplantation. Renal dysfunction was defined as an increase in serum creatinine greater than or equal to 44.2 mumol/L above baseline.nnnRESULTSnCharacteristics of the 43 patients who were given aminoglycosides were similar to those in patients who did not receive aminoglycosides with respect to initial renal function, age, cancer type, and previous exposure to cisplatin. Patients who experienced serious treatment-related toxicities such as hemorrhage or septicemia were more likely to have received aminoglycoside antibiotics (p = 0.005). A multivariate analysis showed that increased duration of neutropenia, advanced patient age, and amphotericin B use were predictors of renal failure. Aminoglycoside therapy did not significantly increase the risk of renal dysfunction.nnnCONCLUSIONSnOur data suggest that with appropriate supportive care measures, aminoglycosides can safely be administered to febrile, neutropenic patients who recently have received high-dose cisplatin therapy.

Cefoperazone/sulbactam versus cefoperazone plus mezlocillin: empiric therapy for febrile, neutropenic bone marrow transplant patients

We conducted a prospective, randomized trial in 132 patients undergoing bone marrow transplantation comparing cefoperazone in combination with sulbactam (S), N = 66, vs. cefoperazone plus mezlocillin (CM), N = 66, as empiric antibiotic therapy for fever and neutropenia. Overall duration of neutropenia was 3-55 (median, 13) days. Forty-one patients had positive initial cultures (S = 22 and CM = 19). Twelve of these 41 patients responded to initial study antibacterial agent treatment (S = 6 and CM = 6). Twenty-nine of 41 patients were withdrawn from study because of clinical deterioration, continued fever, or persistently positive cultures (S = 16 and CM = 13). Of the 90 patients who had culture-negative fever (S = 44 and CM = 46), 44 subjects responded with or without the addition of amphotericin B (S = 21 and CM = 23). Thirty-seven of 90 patients were withdrawn from study due to continued fever or clinical deterioration (S = 17 and CM = 20). Nine patients were withdrawn as a result of rash or diarrhea (S = 6 and CM = 3). We conclude that in patients undergoing bone marrow transplantation, there was no difference in efficacy between cefoperazone/sulbactam and the combination of cefoperazone plus mezlocillin in the empiric treatment of the febrile neutropenic patient. Since the majority of initial infections were due to gram positive bacteria, consideration should be given to broadening initial empiric antibacterial agent therapy with drugs that possess potent activity against these organisms.

Pharmacokinetics, Tolerability and Efficacy of Bolus-Dose vs Continuous-Infusion Granisetron in the Prevention of Vomiting in Patients Undergoing Haematopoietic Stem-Cell Transplantation

AbstractObjective: We compared bolus-infusion with continuous-infusion administration of granisetron antiemetic therapy in patients undergoing haematopoietic stem-cell transplantation.n Methods: We evaluated in a double-blind fashion the efficacy and pharmacokinetics of intravenous bolus-dose granisetron (10 µg/kg bodyweight/day) versus continuous-infusion granisetron (10 µg/kg bodyweight infused over 24 hours) in patients undergoing haematopoietic stem-cell transplantation. Antiemetic therapy was begun within 30 minutes of starting chemotherapy and was continued for 2 days after cytotoxic treatment was completed. All patients also received intravenous dexamethasone 10mg every 12 hours during cytotoxic therapy. Haloperidol 2mg intravenously was permitted as rescue therapy in patients who experienced two or more episodes of vomiting within a 24-hour period.n Results: Forty-three patients (median age 42 years, range 19 to 65 years) were studied: 24 received bolus-dose and 19 continuous-infusion granisetron. Complete success (no vomiting) was observed in nine patients in the bolus-dose group compared with seven in the continuous-infusion group. Success with rescue antiemetic treatment (haloperidol) was observed in 10 patients in the bolus-dose group compared with three patients in the continuous-infusion group. Failures were noted in five bolus-dose and nine continuous-infusion-treated patients. Granisetron pharmacokinetics were determined in five patients receiving the drug by continuous-infusion and in seven patients after bolus-dose administration. Pharmacokinetic parameter values ranged widely but were similar between the two groups. No relationship between granisetron success or failure and granisetron plasma concentration or pharmacokinetic characteristics was observed.n Conclusion: Continuous-infusion granisetron does not appear to possess any antiemetic superiority to bolus-dose administration in the transplant setting.