Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

Should embryos with autosomal monosomy by preimplantation genetic testing for aneuploidy be transferred?: Implications for embryo selection from a systematic literature review of autosomal monosomy survivors.

OBJECTIVE: To review the literature for survival and phenotypes of liveborns with autosomal monosomy to inform decisions regarding transfer of in vitro fertilization-derived embryos reported as monosomic on preimplantation genetic testing for aneuploidy (PGT-A). METHOD: Ovid-Medline and EMBASE were systematically searched to identify published case reports of liveborn individuals with autosomal monosomy, full or mosaic, for a whole chromosome. RESULTS: Fifty-three reports describing 56 individuals with autosomal monosomy met the selection criteria: 1 case each of monosomy 14 and 16, 3 each for monosomy 15 and 18, 1 for group "E", 5 for monosomy 20, 24 for monosomy 21, 7 for monosomy 22, and eleven for a "G" group chromosome. There were no reports with monosomy for the larger chromosomes 1 through 13, nor for chromosomes 17 or 19, autosomes with highest gene density. Most reported individuals had severe handicaps and died in infancy with some surviving longer. CONCLUSION: Given potential for survival of handicapped individuals with autosomal monosomy for chromosomes 14, 15, 16, 18, 20, 21, and 22, low priority should be given to transfer of embryos apparently monosomic for these chromosomes. Couples electing transfer of monosomic embryos should consider amniocentesis for ongoing pregnancies but should be informed of its limitations.

Non-radiation risk factors for leukemia: A case-control study among chornobyl cleanup workers in Ukraine.

BACKGROUND: Occupational and environmental exposure to chemicals such as benzene has been linked to increased risk of leukemia. Cigarette smoking and alcohol consumption have also been found to affect leukemia risk. Previous analyses in a large cohort of Chornobyl clean-up workers in Ukraine found significant radiation-related increased risk for all leukemia types. We investigated the potential for additional effects of occupational and lifestyle factors on leukemia risk in this radiation-exposed cohort. METHODS: In a case-control study of chronic lymphocytic and other leukemias among Chornobyl cleanup workers, we collected data on a range of non-radiation exposures. We evaluated these and other potential risk factors in analyses adjusting for estimated bone marrow radiation dose. We calculated Odds Ratios and 95% Confidence Intervals in relation to lifestyle factors and occupational hazards. RESULTS: After adjusting for radiation, we found no clear association of leukemia risk with smoking or alcohol but identified a two-fold elevated risk for non-CLL leukemia with occupational exposure to petroleum (OR=2.28; 95% Confidence Interval 1.13, 6.79). Risks were particularly high for myeloid leukemias. No associations with risk factors other than radiation were found for chronic lymphocytic leukemia. CONCLUSIONS: These data - the first from a working population in Ukraine - add to evidence from several previous reports of excess leukemia morbidity in groups exposed environmentally or occupationally to petroleum or its products.

How do nurses experience working with adolescents with a diagnosis of 'personality disorder' or 'emerging personality disorder'?

Nurses experience adults with a diagnosis of 'personality disorder' ('PD') as challenging, but nothing is known of their experiences working with young people with a diagnosis of 'PD' or 'emerging PD'. This study aimed to explore the experiences of nurses with this group. Six nurses were interviewed individually and the transcripts analysed employing interpretative phenomenological analysis. Two themes were identified: emotional impact, and conflict and need for support. Participants described powerful emotional responses and heavy time demands as particular challenges. They also reflected on tensions that arose in the wider team and service context. The importance of reflective space, training and the need for specialist approaches, such as therapeutic input, was emphasized by all participants. The study's findings suggest that while there are some similarities to adult services, there are also issues specific to nursing adolescents with 'PD', which merit further attention, including the implications of the lack of diagnostic clarity for treatment approaches and the difficult interpersonal dynamics of the condition. Recommendations for practice include additional training in relation to the theoretical understanding of diagnosis itself and in working therapeutically with young people with the diagnosis, employing approaches that have been found to be useful in adult services.

The Ukrainian-American study of leukemia and related disorders among Chornobyl cleanup workers from Ukraine: I. Study methods.

There are relatively few data on the risk of leukemia among those exposed to external radiation during cleanup operations after the Chornobyl nuclear accident, and results have not been consistent. To investigate this further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses estimated using a new time-and-motion method known as RADRUE described in companion paper II. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration, and residence. All identified cases were reviewed by an international panel of experts; 87 of 111 were confirmed. The dose-response analysis and results are given in companion paper III. As background, we describe herein the design, procedures, outcome of case finding and confirmation, control selection, dose estimation and interviewing of subjects.

Model-based characterization of an amino acid racemase from Pseudomonas putida DSM 3263 for application in medium-constrained continuous processes.

The amino acid racemase with broad substrate specificity from Pseudomonas putida DSM 3263 was overproduced and characterized with respect to application in an integrated multi-step process (e.g., dynamic kinetic resolution) that--theoretically--would allow for 100% chemical yield and 100% enantiomeric excess. Overexpression of the racemase gene in Escherichia coli delivered cell free extract with easily sufficient activity (20-50 U mg(-1) total protein) for application in an enzyme membrane reactor (EMR) setting. Model-based experimental analysis of a set of enzyme assays clearly indicated that racemization of the model substrates D- or L-methionine could be accurately described by reversible Michaelis-Menten kinetics. The corresponding kinetic parameters were determined from progress curves for the entire suitable set of aqueous-organic mixtures (up to 60% methanol and 40% acetonitrile) that are eligible for an integrated process scheme. The resulting kinetic expression could be successfully applied to describe enzyme membrane reactor performance under a large variety of settings. Model-based calculations suggested that a methanol content of 10% and an acetonitrile content of 20% provide maximum productivity in EMR operations. However product concentrations were decreased in comparison to purely aqueous operation due to decreasing solubility of methionine with increasing organic solvent content. Finally, biocatalyst stability was investigated in different solvent compositions following a model-based approach. Buffer without organic content provided excellent stability at moderate temperatures (20-35 degrees C) while addition of 20% acetonitrile or methanol drastically reduced the half-life of the racemase.

Altered glycosylation leads to Tr polyagglutination.

BACKGROUND: Polyagglutination refers to red blood cells (RBCs) that are agglutinated by a high proportion of ABO-matched adult sera but not by cord sera. Polyagglutinable RBCs have been associated with microbial infection, myeloproliferative disorders, and myelodysplasia. Lectins aid in the identification of polyagglutination. CASE STUDY: A Hispanic male infant with mild hemolytic anemia, a "Bernard-Soulier-like" syndrome, intermittent neutropenia, mitral valve regurgitation, ligament hyperlaxity, and mild mental retardation was studied. The patient's Group O RBCs were polyagglutinable; they were agglutinated by normal human sera, several lectins [including Arachis hypogea, Salvia sclarea, Salvia horminum, Glycine max, Ulex europaeus, Griffonia simplicifolia I, and Gr. simplicifolia II], and some monoclonal antibodies. His RBCs were not agglutinated by cord sera, Dolichos biflorus, or Phaseolus lunatus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis on the RBC membranes followed by staining with periodic acid-Schiff stain showed markedly reduced staining of glycophorins A and B. Staining with Coomassie brilliant blue revealed that Band 3 has a faster mobility than normal. CONCLUSIONS: Collectively, the results suggest that the patient's RBCs have a reduction in N-acetylneuraminic acid on both N- and O-glycans, exposing, respectively, beta1,4-galactosidase and beta1,3-galactosidase. The patient likely has an altered glycosyltransferase that results in defective glycosylation in RBCs and other cell lineages. This type of polyagglutination was named Tr.

Malignant islet cell tumor with sarcomatous differentiation.

Malignant mesenchymal neoplasms of the pancreas are rare and malignant islet cell tumors with sarcomatous dedifferentiation are rarer still. We present a case of malignant islet cell tumor with sarcomatous differentiation, which to our knowledge is only the second reported case showing such a combination of morphologic features. Clinically, the neoplasm was not hormonally active and immunohistochemical staining was negative for gastrin, glucagon, insulin and somatostatin. The sarcomatous component strongly reacted with an antibody directed against vimentin, and a minority of cells stained strongly with antisera directed against desmin and smooth muscle actin. The spindle cell component was nonreactive with antibodies directed against Factor VIII. The myogenous direction of differentiation in the present tumor is similar to that seen in the prior case report of malignant islet cell tumor with rhabdomyosarcomatous differentiation.

Cell typing the sensitized transfusion-dependent patient.

Extended red cell typing is required for the management of transfusion-dependent patients to confirm the identity of suspected alloantibodies or determine the specificity of potential additional antibodies that may be formed in the future. Typing may be complicated by the presence of circulating allogeneic cells or a positive direct antiglobulin test. Phenotyping such individuals by hemagglutination is dependent on the separation of a reticulocyte-enriched fraction by differential centrifugation. Flow cytometric typing of reticulocytes is also possible. The effectiveness of these techniques is limited in those who are heavily transfused or have low reticulocyte counts. Heavily transfused patients with sickle cell anemia may be typed, however, following hypotonic lysis of allogeneic cells. In patients with a positive direct antiglobulin test, sensitized cells are usually typed with either direct agglutinating antisera and/or IgG antisera following elution of the autoantibody. Inactivation of some antigens during the elution process or the lack of some antisera specificities limit such typing. By designing appropriate oligonucleotide primers, polymerase chain reaction (PCR) amplification of target gene sequences for most blood group systems and the identification of a large number of their allelic specificities is now possible. Peripheral blood leukocytes can be used as the DNA source. Restriction fragment length polymorphism determination is widely adopted for the identification of allelic specificity of the amplified target sequence. Alternate strategies, including allele-specific PCR, are often employed if the genetic basis of the polymorphism is more complex than a single nucleotide substitution, or if it does not create or ablate a restriction endonuclease cleavage site. These techniques may permit genotyping of sensitized transfusion-dependent patients, and can improve transfusion safety and efficacy.

Functional urinary tract obstruction developing in fetuses with isolated gastroschisis.

OBJECTIVE: To evaluate the frequency and natural history of urinary tract abnormalities developing in fetuses presenting with initially isolated gastroschisis. METHODS: Serial ultrasounds were performed prospectively on fetuses identified by our prenatal diagnosis program as having a gastroschisis. When abnormalities in the urinary tract were identified prenatally, newborns were evaluated by a pediatric urologist. RESULTS: Over a 1-year period four out of 12 fetuses with gastroschisis developed deformations of the urinary tract. In three fetuses the bladder herniated through the abdominal wall defect. Two also had upper tract dilatation. A fourth fetus developed bilateral hydronephrosis with a normally situated bladder. Once the gastroschisis was repaired none of the newborns had evidence of structural obstruction of the urinary tract, however, hydronephrosis with or without reflux persisted for several months. CONCLUSIONS: Deformations of the fetal urinary tract can develop secondary to gastroschisis. They do not appear to represent separate malformations and evaluation with fetal karyotyping may not be indicated. When hydronephrosis is present ongoing urologic evaluation of the neonate is indicated.

Hemostatic defects in massive transfusion: rapid diagnosis and management.

Severe hemostatic defects that occur during massive transfusion are related to the volume of blood transfused, preexisting hemostatic abnormalities, concomitant pathologic changes, and therapeutic maneuvers. The relative role of each factor in the bleeding can be rapidly determined by using routine clinical laboratory tests. This determination requires an understanding of the properties of selected clotting factors, what coagulation screening tests measure, how these tests behave as the levels of factors change, and test profiles characteristic of different defects. Screening tests include platelet count, prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen level. These tests are generally available on an emergent basis and can be completed within 25 minutes. The pattern associated with hemodilution is universal in massive transfusion. Patterns characteristic of the other pathologic processes that may be encountered are simply superimposed on the characteristics of hemodilution. Successful management of the contributing causes of bleeding depends on the administration of the appropriate blood components in the dose necessary to ensure that the levels of platelets and clotting factors are returned to and maintained at hemostatic levels.

Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: how to cumulate?

The Food Quality Protection Act (FQPA) of 1996 requires the U.S. EPA to consider the "cumulative effects" of pesticides and other substances that have a "common mechanism of toxicity." Several different methods for combining the exposures to estimate the risk of groups of common mechanism chemicals with different potencies and exposure characteristics are critically evaluated. These are the hazard index (HI), toxicity equivalence factor (TEF), and combined margin of exposure (MOE(T)) procedures as well as the point of departure index (PODI) and cumulative risk index (CRI) methods that are the reciprocals of the HI and MOE(T) approaches, respectively. Each of these methods ideally requires, at a minimum, the availability of in vivo toxicology data for the same toxicological endpoint in the same animal species. Furthermore, all assume that the effects of the individual components in the mixture are independent in nature (i.e., are additive rather than synergistic or antagonistic) and that the dose-response functions for all compounds have a similar slope. The point of departure (POD), preferably the dose corresponding to a given effect level (e.g., the ED(10)), can be used as a measure of the relative potency of the different chemicals in the group. If appropriate exposure and toxicology data are available, and the chemicals in the group have a common uncertainty factor (UF), all the procedures yield a numerically identical result. The fact that different chemicals in the group often have different UFs raises issues for all summation procedures and, in the case of the TEF approach, the UF of the index chemical selected dictates the final result of the assessment. A major distinction between the different methods for addition is the point in the process at which uncertainty is considered. The HI and CRI approaches are problematic because they require application of policy-driven UFs (in the form of RfDs) at that stage of the process where exposure should be expressed in terms of potency. In contrast, the PODI and MOE(T) approaches require application of a single group UF(G) at the end of the risk assessment process although they will also accommodate the application of data-based adjustments earlier in the analysis. Importantly, both the PODI and the MOE(T) approaches allow policy- and data-driven UFs to be separated and thus make the process more transparent; these should be considered the methods of choice for cumulative risk assessment. Assignment of a single group UF is somewhat different from developing an UF for a single chemical and the total weight of evidence available in the group database can be used to advantage to reduce the UFs that need to be applied to the group. This larger database can also be used to refine the PODs for individual members of the group. It is important to emphasize that there remains a great deal of scientific uncertainty about how to proceed with cumulative risk assessment as described in the FQPA. The serious difficulties associated with defining "common mechanism of toxicity" and "concurrent exposure" combined with the current paucity of data and methodology required to conduct cumulative risk assessment suggest that the procedure is not yet ready for use in pesticide regulation.

Trisomy 2p syndrome: a fetus with anencephaly and postaxial polydactyly.

We report on a male fetus with partial trisomy 2p21-2pter and monosomy 15q26-15qter due to t(2,15)(p21;q26). This fetus had a typical trisomy 2p phenotype including minor facial anomalies, musculoskeletal defects and two unusual findings: polydactyly and anencephaly. The observation of anencephaly adds support to the theory that genetic material mapping to chromosome band 2p24 is involved in neural tube development. In addition, we propose that a gene on 2p23 may play a role in the morphogenetic patterning of hands and feet.

Amitriptyline absorption in a patient with short bowel syndrome.

Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations.

CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer.

Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD34+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 10(9)/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 10(9)/L (range 6 x 10(9)/L-176 x 10(9)/L). Eight patients (12%) had platelet nadir <20 x 10(9)/L, and all recovered their counts to >20 x 10(9)/L on day 7. There was no clinical difference in days to engraftment between women receiving <2 or > or =2 x 10(6) CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of > or =1 x 10(6) CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 10(9)/L was 10 days (range 9-15), and platelet recovery to >20 x 10(9)/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving > or =2 x 10(6) CD34+/kg versus <2 x 10(6)CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p < 0.01). Ninety-eight percent of patients infused with > or =2 x 10(6) CD34+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of > or =2 x 10(6) CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than <2 x 10(6) CD34+ cells/kg (9 days versus 10 days,p = 0.01), but a dose > or =3 X 10(6) CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.

Managing atrial fibrillation in active patients and athletes.

Atrial fibrillation in young or middle-aged active patients can often be managed with medication. Evaluation should address associated conditions and predisposing factors such as idiopathic hypertrophic subaortic stenosis, Wolff-Parkinson-White syndrome, congenital heart disease, hyperthyroidism, excess alcohol or other drug use, and exercise-induced catecholamine release. Diagnostic studies may include an ECG, 24-hour Holter or event monitoring, exercise treadmill testing, stress echocardiography, electrophysiologic studies, and laboratory testing. Electrocardioversion provides rapid, predictable treatment, but ablation therapy is sometimes needed.

Effects of long-term storage at -90 degrees C of bone marrow and PBPC on cell recovery, viability, and clonogenic potential.

Autologous BM and PB HPC are usually stored from weeks to months until reinfusion after myeloablative chemotherapy. HPC have been stored for up to 16 months at -90 degrees C, using a mixture of 5% DMSO, 6% hydroxyethyl starch (HES), and 4% HSA as a cryoprotectant. Long-term storage (LTS) has usually entailed rate-controlled freezing using 10% DMSO and preservation in liquid nitrogen. The effects of LTS at -90 degrees C on the in vitro cell recovery, viability, and colony-forming unit-granulocyte macrophage (CFU-GM) clonogenic potential of autologous HPC that were not transplanted was studied. Sixteen BM and sixteen PB HPC had been cryopreserved for a median of 53 months (range 27-71) and 35 months (range 26-78), respectively. Samples of frozen HPC were thawed after 48 h, and the nucleated cell count, viability by trypan blue exclusion, and culture for CFU-GM were obtained. Following LTS, the cells were thawed and examined using the same assays. No difference in the median percentage recovery of nucleated cells was found in either the BM or PB HPC between the samples stored for 48 h and after LTS (5.73 x 10(9) versus 5.61 x 10(9) and 6.20 x 10(9) versus 5.78 x 10(9), respectively). In addition, no difference in median percentage viability was found in either the BM or PB HPC sampled at 48 h and at the end of LTS (75% versus 74% and 75% versus 76%, respectively). Finally, the median number of CFU-GM cultured from BM HPC at 48 h was 2.41 x 10(5) (range 0.33-11.01 x 10(5)) and at the end of LTS was 1.93 x 10(5) (range 0.32-10.55), representing a median recovery of 93% (range 19%-308%). Similarly, the median number of CFU-GM cultured from PB HPC was 1.66 x 10(5) (range 0-50.57) and at the end of LTS was 0.93 x 10(5) (range 0-44.9), representing a median recovery of 80% (range 36%-165%). This difference in percentage recovery was not significant (p = 0.514). There was poor correlation between the number of nucleated cells harvested and the percentage recovery of nucleated cells, cell viability, or CFU-GM for either the BM or PB HPC. Similarly, there was poor correlation between the number of CFU-GM in the harvest and their percentage recovery following LTS for both BM and PB HPC. Finally, there was poor correlation between the storage time of the BM or PB HPC and the percentage recovery of nucleated cells, cell viability, and CFU-GM. These data suggest that LTS of HPC at -90 degrees C is not associated with decreased recovery of nucleated cells or in vitro viability and is associated with only a modest decrease in clonogenic potential. This indicates that storage of HPC at -90 degrees C for periods in excess of 3 years is possible.