Prospective study of mobilization kinetics up to 18 hours after late-afternoon dosing of plerixafor.

BACKGROUND: The current FDA-approved time interval between plerixafor dosing and apheresis initiation is approximately 11 hours, but this time interval is impractical for most care providers. Few studies have examined mobilization kinetics beyond 11 hours in multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) patients. Therefore, this study's intent was to analyze an interval of 17 to 18 hours between plerixafor dosing and apheresis initiation. STUDY DESIGN AND METHODS: In 11 patients with MM or NHL, 240 µg/kg plerixafor was administered at 5 p.m. on Day 4 of granulocyte-colony-stimulating factor (G-CSF) mobilization. Peripheral blood (PB) CD34+ and CD34+CD38- concentrations were enumerated every 2 hours until 7 a.m. and immediately before apheresis on Day 5, for a total interval time of 17 to 18 hours after plerixafor. Data were analyzed using mixed-model analysis of repeated measures and paired t testing. RESULTS: Ten of the 11 subjects achieved a CD34+ product count of more than 2 × 10(6) /kg with a single leukapheresis procedure. All 10 had a preplerixafor PB CD34+ concentration ([CD34+]) of at least 10/µL. PB [CD34+] was not different between 10 and 18 hours after plerixafor (p = 0.8). In contrast, PB CD34+CD38- concentrations significantly increased from 10 to 18 hours after plerixafor (p = 0.03). CONCLUSIONS: In MM and NHL patients with adequate preplerixafor [CD34+], leukapheresis initiated 14 to 18 hours after plerixafor and G-CSF mobilization may not impair adequate CD34+ collection and may increase more primitive CD34+CD38- collection. In this subset of patients, late-afternoon dosing of plerixafor at 5 p.m. with initiation of next-day apheresis as late as 11 a.m. appears feasible without loss of efficacy.

Prospective cohort study of the circadian rhythm pattern in allogeneic sibling donors undergoing standard granulocyte colony-stimulating factor mobilization.

INTRODUCTION: Prior in vivo murine studies suggest circadian oscillations for hematopoietic stem cell release, which are maintained following administration of granulocyte colony-stimulating factor (G-CSF) or plerixafor. Furthermore, retrospective data analysis of healthy donors who underwent G-CSF-induced mobilization demonstrated significantly increased CD34(+) cell yields when collected in the afternoon compared with the morning. METHODS: A prospective study was conducted to directly examine the number of peripheral blood CD34(+) and CD34(+)CD38- progenitor/stem cells at baseline and then every 6 hours for 24 hours on days 4 to 5 of G-CSF (10 µg/kg/day in the morning) mobilization in 11 allogeneic donors. Data were analyzed using mixed-model analysis of repeated measures. RESULTS: Whereas we observed a significant increase in CD34(+) cell counts toward the evening, counts were then sustained on the morning of day 5. The correlation between CD34(+)CD38- cell counts and the less defined CD34(+) populations was weak. CONCLUSIONS: Our results suggest that the pharmacodynamic activity and timing of G-CSF may alter endogenous progenitor rhythms. Donor age, medical history, and medications may also impact circadian rhythm. Further studies should examine the circadian rhythm at the peak of G-CSF mobilization and should consider potential confounders such as the time of G-CSF administration and the age of the subjects.

Nephrogenic adenoma: immunohistochemical evaluation for its etiology and differentiation from prostatic adenocarcinoma.

CONTEXT: Nephrogenic adenoma is a rare benign lesion of the urinary tract. Owing to its strong association with a history of urinary tract irritation, nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof of this association has been found. More recent investigation has pointed to a renal tubular cause. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic carcinoma, particularly when dealing with lesions from the prostatic urethra. OBJECTIVE: To elucidate a possible histogenic relationship between nephrogenic adenoma and renal tubules, and also to evaluate the role of immunohistochemistry in the diagnostic distinction between nephrogenic adenoma and prostate carcinoma. DESIGN: Immunohistochemical studies were performed for P504S, prostate-specific antigen, CD10, p63, and epithelial membrane antigen on 9 cases of nephrogenic adenoma, 10 cases of normal renal parenchyma, and 10 cases of prostatic tissue, both benign and malignant. RESULTS: Nephrogenic adenoma shares the same immunohistochemical profile as distal renal tubules: both are positive for P504S and epithelial membrane antigen and negative for p63, CD10, and prostate-specific antigen. Prostatic adenocarcinoma tissue was positive for P504S and prostate-specific antigen, and normal prostatic gland tissue was positive for prostate-specific antigen and negative for P504S; p63-stained basal cells in normal prostatic gland tissue but did not react with prostatic adenocarcinoma tissue. The CD10 inconsistently stained normal and neoplastic prostatic gland tissue. Epithelial membrane antigen stain was negative in prostatic carcinoma, with rare occasional reactivity in normal prostatic glands. CONCLUSION: These findings provide supporting evidence that nephrogenic adenoma is derived from distal renal tubules. Our results also demonstrated that the combination of P504S and prostate-specific antigen with epithelial membrane antigen is a valuable tool in distinguishing prostatic carcinoma from nephrogenic adenoma.

Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone.

Studies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks). Twenty-four-hour mean serum testosterone rose in every subject, from a mean of 290 +/- 165 ng/dL to a mean of 403 +/- 170 (P <.0003); 24-hour mean serum estradiol decreased in every subject, from a mean of 40 +/- 10.8 pg/mL to a mean of 29 +/- 6.7 (P <.004); and 24-hour mean serum luteinizing hormone (LH) increased in every subject, from a mean of 14.3 +/- 4.1 mIU/mL to a mean of 19.3 +/- 5.1 (P <.004). The rise in mean LH was due to an increase in the amplitude of the individual secretory pulses, especially at night. Twenty-four-hour mean serum estrone decreased nonsignificantly, from 48 +/- 14 pg/mL to 39 +/- 6.4, and 24-hour mean serum FSH increased nonsignificantly, from 13.5 +/- 5.3 mIU/mL to 15.0 +/- 5.4. The results are in accordance with the hypothesis, in that inhibition of estrogen biosynthesis (through administration of the aromatase inhibitor testolactone) results in alleviation of the HHG of our obese male subjects.

The nested variant of urothelial carcinoma: clinicopathology of 2 cases.

The nested variant of urothelial carcinoma is a recently described bladder tumor entity with a rare incidence. Two cases of this disease are presented in this report; the patients in both cases were elderly men, with a predominant involvement of the trigone region. Histologically, the tumor cells were arranged in ill-defined nests and had low-grade nuclear features. Both cases had a diffusely infiltrating growth pattern with widespread local disease at cystectomy. Strong immunohistochemical staining for p63 in the neoplastic cells supports the urothelial cell nature of this neoplasm. High p53 and Ki-67 indices of this tumor correlate with the aggressiveness of this subtype.

Lymphoid progenitor cells in human tonsils.

To investigate the occurrence of lymphoid progenitor cells in human tonsils, we studied tonsils from children and adults by immunohistochemistry by using a panel of antibodies to antigens associated with lymphoid progenitor cells, including terminal deoxynucleotidyl transferase (TdT), CD10 (CALLA), CD34, CD99 (p30/32mic2), and CD117 (c-kit), and compared them to reactive lymph nodes. Lymphoid progenitor cells, positive for TdT, CD10, and CD99, but not CD34 or CD117, were readily identified in tonsils from children and adults (TdT, 14 of 15; CD10, 15 of 15; CD99, 11 of 15), but were rarely present in lymph nodes (TdT, 1 of 8; CD10, 1 of 8; CD99, 0 of 8). Lymphoid progenitor cells in tonsils were localized to discrete foci at the periphery of lymphoid lobules adjacent to fibrous septae. Lymphoid progenitor cells are present in human tonsils, and the tonsils are a potential site of postnatal lymphopoiesis. The presence of lymphoid progenitor cells in human tonsils should not be confused with lymphoblastic lymphoma or leukemia.

Lymph node infarction. An immunohistochemical study of 11 cases.

CONTEXT: The etiology of lymph node infarction may be difficult or impossible to determine by histologic examination. Lymph node infarction is followed by malignant lymphoma in some but not all patients. The role of immunohistochemistry in the evaluation of lymph node infarction is not well defined. Although it is widely believed that necrotic tissue is not suitable for immunohistochemical study, this view may be inaccurate. OBJECTIVE: To determine whether lymphoid antigens are preserved in infarcted lymph nodes and to determine the utility of immunohistochemical staining in the evaluation of lymph node infarction. DESIGN: Retrospective immunohistochemical study of infarcted lymph nodes using archival formalin-fixed, paraffin-embedded tissue. SETTING: Academic medical center. PATIENTS: Eleven adult patients with lymph node infarction retrieved from pathology files. MAIN OUTCOMES MEASURES: Results of immunohistochemistry, diagnosis of lymphoma. RESULTS: Preservation of lymphoid antigens was observed in 4 of 6 cases of lymph node infarction associated with malignant lymphoma, including 3 of 5 cases of diffuse large B-cell lymphoma and 1 case of peripheral T-cell lymphoma. Nonspecific staining was not encountered. In 1 case, in which an infarcted lymph node showed a benign pattern of lymphoid antigen expression, lymphoma has not developed after 5 years. CONCLUSION: Lymphoid antigens are frequently preserved in cases of lymph node infarction, and immunohistochemical study of infarcted lymph nodes may provide clinically useful information.