Terminology and labeling of cellular products-2: Implementation plan.

The publication of new standards for terminology and labeling marks an important step in ensuring consistency and traceability of cellular therapies at the global level. However, it is only with the widespread implementation of the standard that the benefits can be truly realized. This paper provides guidance on the practical aspects of adopting these new standards for organizations with differing current levels of computerization. It discusses project management, equipment, licensing, and validation topics.

Terminology and labeling of cellular products: 1. Standards.

The International Cellular Therapy Coding and Labeling Advisory Group was established to address the growing need for standardization of terminology and labeling for cellular therapy products as a result of increasing international transfer of these products. This paper presents new standards for terminology and labeling. These standards have been developed through a consultative process and are supported by key professional and accreditation bodies. By using these standards, together with the unique donation identification numbers and international product reference tables provided by the International Society of Blood Transfusion (ISBT) 128 Standard, consistency and traceability can be assured at the global level. A companion paper provides guidance on the implementation of the ISBT 128 system.

Evaluation of an automated instrument for viability and concentration measurements of cryopreserved hematopoietic cells.

Two important parameters for determination of deleterious effects of cellular processing on hematopoietic progenitor cells are cell viability and concentration. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital evaluated the Beckman Coulter Vi-Cell automated instrument for the measurement of these two parameters. Using 33 thawed hematopoietic progenitor cell samples, automated Vi-Cell viability results were compared to those obtained using the standard trypan blue manual method. In addition, cell concentrations from these samples were compared with results from the Model Z2 Coulter Counter. Chinese Hamster Ovary cells were used for the evaluation of Vi-Cell linearity at the Beckman Coulter Cellular Analysis Development Center. Significant correlation was obtained when the two methods were compared for both cell concentration and percentage viability (P < .0001). The results of the linearity study indicated that the Vi-Cell is linear from approximately 5 x 10(4) to greater than 1 x 10(7) cells/mL. The Vi-Cell uses sample volumes as low as 0.5 mL; cell diameters may be 2 to 70 microns. The Vi-Cell automated instrument offers many significant advantages for cell analyses in today's busy laboratory environment.

CD34 selection using three immunoselection devices: comparison of T-cell depleted allografts.

BACKGROUND: T-cell depletion of allografts markedly reduces the incidence of GvHD following BMT. The approach taken at our Center has utilized the physical separation method of counterflow centrifugal elutriation (CCE), augmented by recovery of stem cells from lymphocyte-rich fractions by immunoaffinity selection of CD34(+) stem cells. We wanted to compare the performance characteristics of three commercially available selection devices, as well as the clinical outcomes of patients who received allografts engineered by the different devices. METHODS: BM allografts were prepared for patients undergoing BMT for hematologic malignancies. BM cells were separated into lymphocyte-rich and lymphocyte-depleted fractions using CCE, followed by recovery of CD34(+) cells from the lymphocyte-rich fraction using one of three immunoselection devices [CellPro CEPRATE, Nexell Isolex 300i (software version 2.5) and AmCell CliniMACS]. Allografts consisted of the lymphocyte-depleted fraction plus the CD34-selected fraction. RESULTS: Yields of CD34(+) cells were comparable for the three devices. However, there were significant differences in purity (CEPRATE < Isolex 300i < CliniMACS) and time from start of fractionation to infusion (CEPRATE < CliniMACS < Isolex 300i). More technical problems were encountered with the Isolex 300i device. Allograft compositions were comparable. Transplant outcomes (engraftment and incidence of GvHD) also were comparable. DISCUSSION: Qualitatively and quantitatively, allografts prepared with the CEPRATE, Isolex 300i (v 2.5) and CliniMACS devices should be considered comparable for use in this setting and probably also for direct T-cell depletion of BM.

Using point-of-care CD34 enumeration to optimize PBSC collection conditions.

BACKGROUND: A PBSC graft containing 4-5 x 10(6) CD34(+) cells/kg is considered optimal in terms of durable engraftment. Tracking CD34 kinetics via point-of-care testing during PBSC mobilization could determine which (and when) patients will yield an optimal product. We evaluated whether microvolume fluorimetry (MVF) would be useful in optimizing PBSC mobilization/harvest and if it will shorten our standard 6 h collection. METHODS: Absolute CD34 values were obtained using the IMAGN 2000 and STELLer CD34 assay (50 microL sample volume). Peripheral blood (PB) CD34 values from 30 patients undergoing PBSC mobilization were used to generate a PB CD34-based algorithm that would predict collection day/duration of apheresis. The algorithm was then used prospectively to collect PBSC products on 50 hematologic malignancy (HM) patients. RESULTS: Using the algorithm, patients were assigned to either a 6 (11-20 CD34/microL), 4 (21-49 CD34/microL) or 2 (> or = 50 CD34/microL) h collection. Patients with a CD34 value < or = 10/microL were re-tested. All patients (n = 43) predicted to mobilize reached the optimal CD34 (4-5 x 10(6)/kg) value with 1.0 apheresis procedure; seven patients had < or = 10/microL (nonmobilizers). The majority (75%) had apheresis charges decreased by 33-66%; 47% only required a 2 h procedure and 28% required 4 h. All patients demonstrated rapid trilineage engraftment. DISCUSSION: Absolute PB CD34 measurement using MVF offers a rapid and reliable approach to obtaining optimal PBSC products with minimal technical expertise. Although not a replacement for conventional flow cytometry, it meets the requirements for a point-of-care procedure.

Postoperative epidural morphine is safe on surgical wards.

The use of epidural morphine for postoperative analgesia outside of intensive care units remains controversial. In this report our anesthesiology-based acute pain service documents experience with 1,106 consecutive postoperative patients treated with epidural morphine on regular surgical wards. This experience involved 4,343 total patient days of care and 11,089 individual epidural morphine injections. On a 0-10 verbal analog scale, patient-reported median pain scores at rest and with coughing or ambulation were 1 (inter-quartile range 3) and 4 (interquartile range 4), respectively. The incidence of side effects requiring medication were as follows: pruritus 24%, nausea 29%, and respiratory depression 0.2%. There were no deaths, neurologic injuries, or infections associated with the technique. Migration of epidural catheters into the subarachnoid space and into epidural veins each occurred twice. Overall, 1,051 of the 1,106 patients (95%) experienced none of the following problems: catheter obstruction, premature dislodgement, painful injections, catheter migration, infection, or respiratory depression. We conclude that postoperative pain can be safely and effectively treated with epidural morphine on surgical wards.

Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery.

The management of postoperative pain with continuous epidural fentanyl infusion was compared with continuous intravenous fentanyl infusion. In a randomized, doubleblind protocol we prospectively studied 20 patients undergoing repair of the anterior cruciate ligament of the knee. The quality of analgesia and the incidence of side effects were documented. Compared with patients receiving continuous intravenous fentanyl infusion, at 18 h postoperatively patients given continuous epidural fentanyl infusion reported similar pain scores both at rest (22 +/- 25 vs 27 +/- 21, P = 0.52) and with ambulation (59 +/- 18 vs 56 +/- 22, P = 0.82). Plasma fentanyl levels were 1.8 +/- 0.4 and 1.7 +/- 0.4 ng/mL (P = 0.91) for the intravenous and epidural groups, respectively. There were no significant differences in the incidence of nausea, pruritus, or urinary retention. There was no respiratory depression in either group. We conclude that when compared with continuous intravenous fentanyl infusion, continuous epidural fentanyl infusion offers no clinical advantages for the management of postoperative pain after knee surgery.

Regional anesthesia for hepatic arterial embolization.

Hepatic arterial embolization (HAE) has been utilized for treatment of unresectable primary and metastatic hepatic malignancies. While palliation results from this procedure, one of the major drawbacks to its use is the immediate short-term side effects, especially the right upper quadrant and epigastric pain experienced by all patients. High doses of intravenous narcotics have been used for pain control. The data on 18 patients who received a celiac plexus block immediately prior to 31 HAE procedures were compared with those on 19 control patients who underwent 42 HAE procedures without celiac plexus block. All patients who received a celiac plexus block had relief of pain without requiring intravenous analgesic both during the procedure and for the first 8 hours after HAE. These patients also subsequently received substantially lower dosages of analgesics than the control subjects. Two patients had transient hypotension due to the celiac plexus block, but no other complications occurred. It is recommended that patients undergoing HAE first receive a celiac plexus block for pain control.

Clinical toxicology of cocaine.

Recent widespread abuse of cocaine has resulted in an alarming increase in emergency department admissions for acute treatment of this toxic drug. Highly publicized cocaine-associated deaths of prominent athletes have awakened both the medical community and the general public to the possible devastating effects of this so-called 'champagne of drugs'. A potent central nervous system stimulant, cocaine produces symptoms that include changes in activity, mood, blood pressure, cardiac rhythm, respiration and body temperature. The adverse effects of cocaine, which may progress rapidly to death, include cerebrovascular accidents, myocardial infarction, sudden cardiac arrhythmias, pneumomediastinum, rhabdomyolysis with myoglobinuric renal failure and intestinal ischaemia. In addition, cocaine has been implicated in obstetric and neonatal complications. Because of the exceedingly rapid progression of the 'cocaine reaction' to a fatal outcome, it is imperative that clinicians know how to recognise and manage the symptoms of cocaine overdose.

Epidural morphine after anterior cruciate ligament repair: a comparison with patient-controlled intravenous morphine.

To compare the management of postoperative pain using morphine administered by epidural catheter with intravenous patient-controlled analgesia (PCA), we prospectively studied 47 consecutive cases involving repair of the anterior cruciate ligament of the knee. Both the quality of analgesia and the incidence of side effects were documented. Compared with patients receiving PCA morphine, patients given epidural morphine reported significantly lower pain scores both at rest (0.7 +/- 1.1 versus 3.4 +/- 2.1, P less than 0.01) and with mobilization (3.2 +/- 2.1 versus 6.1 +/- 2.1, P less than 0.01). Although patients receiving epidural morphine had a greater incidence of urinary retention, there were no significant differences in the incidence of nausea or pruritus. There was no respiratory depression in either group. We conclude that epidural morphine provides superior analgesia with a clinically inconsequential increase in side effects. Further, epidural morphine may have special advantages when early mobilization is indicated.

Prophylactic transdermal scopolamine patches reduce nausea in postoperative patients receiving epidural morphine.

To evaluate the efficacy of prophylactic transdermal scopolamine in reducing nausea associated with postoperative epidural analgesia, we studied 32 healthy adult women undergoing major gynecologic surgery. The patients were randomized in a double blind fashion to receive either a cutaneous scopolamine patch or a visually identical cutaneous placebo patch. Postoperative analgesia was provided solely with epidural morphine. Nausea was treated with metoclopramide and droperidol. At 24 hours postoperatively, the mean nausea score was significantly lower with scopolamine than with placebo (1 +/- 2 vs 51 +/- 42, respectively, P less than 0.05). The number of patients reporting "zero nausea" was significantly greater with scopolamine patches than with placebo patches (13 vs 1, P less than 0.01). The mean number of times antiemetic drugs were administered per patient was lower with scopolamine than with placebo patches (0.2 +/- 0.4 vs 2.8 +/- 2.6, P less than 0.05). It is concluded that prophylactic transdermal scopolamine patches reduce nausea in postoperative patients receiving epidural morphine.

The use of labetalol in the management of cocaine crisis.

We report a case of successful resuscitation and clinical management in a 31-year-old man who allegedly ingested 20 g of cocaine hydrochloride. The physiologic and pharmacologic mechanisms of cocaine toxicity are reviewed. The use of labetalol in resolving the cardiovascular crisis is specifically detailed.

Comparison of halothane and isoflurane for rapid anesthetic induction.

To study the hypothesis that isoflurane will induce anesthesia faster than halothane when given by a single vital capacity breath technique, we studied 20 ASA I and II adults who breathed approximately 4.5 MAC equivalents of either vapor. The patients, randomly assigned to receive either agent, were fully preoxygenated and monitored for cardiovascular, respiratory, and EEG parameters. All subjects were premedicated with 5 micrograms/kg fentanyl IV 5 min before induction. Time to loss of consciousness was significantly longer with halothane than with isoflurane (86 +/- 4 vs 38 +/- 2 sec, respectively) although there were no clinically remarkable differences in cardiovascular or respiratory variables. Patients given halothane had a greater excitatory phase on EEG, whereas those given isoflurane had low frequency predominance. Overall rapid inhalation induction was well-received by all patients and was significantly faster with isoflurane.