CXCR4 signaling controls dendritic cell location and activation at steady state and in inflammation.

Dendritic cells (DCs) encompass several cell subsets that collaborate to initiate and regulate immune responses. Proper DC localization determines their function and requires the tightly controlled action of chemokine receptors. All DC subsets express CXCR4, but the genuine contribution of this receptor to their biology has been overlooked. We addressed this question using natural CXCR4 mutants resistant to CXCL12-induced desensitization and harboring a gain of function that cause the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS), a rare immunodeficiency associated with high susceptibility to the pathogenesis of human papillomavirus (HPV). We report a reduction in the number of circulating plasmacytoid DCs (pDCs) in WHIM patients, whereas that of conventional DCs is preserved. This pattern was reproduced in an original mouse model of WS, enabling us to show that the circulating pDC defect can be corrected upon CXCR4 blockade and that pDC differentiation and function are preserved, despite CXCR4 dysfunction. We further identified proper CXCR4 signaling as a critical checkpoint for Langerhans cell and DC migration from the skin to lymph nodes, with corollary alterations of their activation state and tissue inflammation in a model of HPV-induced dysplasia. Beyond providing new hypotheses to explain the susceptibility of WHIM patients to HPV pathogenesis, this study shows that proper CXCR4 signaling establishes a migration threshold that controls DC egress from CXCL12-containing environments and highlights the critical and subset-specific contribution of CXCR4 signal termination to DC biology.

Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalation and extension study in 8 adult patients with genetically confirmed WHIM syndrome. Mavorixafor is an oral small molecule selective antagonist of the CXCR4 receptor that increases mobilization and trafficking of white blood cells from the bone marrow. Patients received escalating doses of mavorixafor, up to 400 mg once daily. Five patients continued on the extension study for up to 28.6 months. Mavorixafor was well tolerated with no treatment-related serious adverse events. At a median follow-up of 16.5 months, we observed dose-dependent increases in absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). At doses ≥300 mg/d, ANC was maintained at >500 cells per microliter for a median of 12.6 hours, and ALC was maintained at >1000 cells per microliter for up to 16.9 hours. Continued follow-up on the extension study resulted in a yearly infection rate that decreased from 4.63 events (95% confidence interval, 3.3-6.3) in the 12 months prior to the trial to 2.27 events (95% confidence interval, 1.4-3.5) for patients on effective doses. We observed an average 75% reduction in the number of cutaneous warts. This study demonstrates that mavorixafor, 400 mg once daily, mobilizes neutrophil and lymphocytes in adult patients with WHIM syndrome and provides preliminary evidence of clinical benefit for patients on long-term therapy. The trial was registered at www.clinicaltrials.gov as #NCT03005327.

Pre-treatment vitamin B12, folate, ferritin, and vitamin D serum levels in patients with warts: a retrospective study.

AIM: To compare the serum levels of 25-hydroxyvitamin D, ferritin, folate, vitamin B12, zinc, and thyroid stimulating hormone between patients with warts and healthy individuals. METHODS: This retrospective study enrolled 40 patients with warts and 40 healthy individuals treated at the Ufuk University Hospital, Ankara, between July and December 2017. Serum levels of 25-hydroxyvitamin D, ferritin, folate, vitamin B12, zinc, and thyroid stimulating hormone status were evaluated retrospectively. RESULTS: Participants with and without warts had similar mean serum 25-hydroxyvitamin D, ferritin, folate, zinc, and thyroid stimulating hormone levels. However, patients with warts had significantly lower mean serum vitamin B12 level (P=0.010). Patients with warts non-significantly more frequently had decreased serum levels of 25-hydroxyvitamin D, ferritin, and folate (P=0.330, P=0.200, P=0.070, respectively). CONCLUSION: Patients with warts may require evaluation of serum levels of vitamin B12, folate, ferritin, and vitamin D.

Coenzyme Q10, Zinc and MDA levels in verruca vulgaris

Background/aim: Verruca vulgaris is a benign disease characterized with papillomas on the skin and mucosa. The aim of this study was to investigate the serum levels of coenzyme Q10, MDA, and zinc as well as the lipid profile of verruca vulgaris patients and examine the relationship between these parameters and clinical manifestations of the disease. Materials and methods: The study included 49 verruca vulgaris patients (mean age: 32.01 ± 14.20 years; 22 males, 27 females) and 40 healthy volunteers (mean age: 31.63 ± 8.98 years; 21 males and 19 females). Coenzyme Q10 levels were assessed by using an enzyme- linked immunosorbent assay. Serum MDA levels were measured spectrophotometrically. Zinc levels were measured using a Perkin Elmer AAnalyst 800 atomic absorption spectrometer with a deuterium background correction and additional standard techniques. Results: The coenzyme Q10 levels were found to be higher in the verruca vulgaris group compared to the healthy volunteers. However, this increase was not statistically significant (P = 0.195). Zinc levels were significantly lower in the verruca vulgaris group compared to the healthy volunteers (P = 0.002). In the patient group, MDA levels and HDL levels were significantly higher compared to the healthy volunteers (P = 0.023 and P = 0.004, respectively). Additionally, there was no statistically significant difference between the groups in the CoQ10/Total cholesterol ratio (P = 0.433). Conclusion: Reduced serum zinc levels and increase of oxidative stress in verruca vulgaris may be a factor responsible for development of verruca vulgaris.

High Ambient Solar UV Correlates with Greater Beta HPV Seropositivity in New South Wales, Australia.

BACKGROUND: Human papillomavirus (HPV) infection is highly prevalent worldwide and may have a role, with sun exposure, in causing cutaneous squamous cell carcinoma. Little is known about the relationship of UV exposure and seroprevalence of cutaneous HPVs in the general population. METHODS: Using multiplex serology, we estimated the seroprevalence of 23 beta and 7 gamma HPVs and 7 other antigens (mu HPV1, HPV63, nu HPV41, alpha HPV16; polyomaviruses HPyV7 and MCV; p53) in a population-based sample of 1,161 Australian 45 and Up Study participants with valid data from blood specimens collected from 2010 to 2012. We calculated prevalence ratios (PR) for the association of each antigen with residential ambient solar UV and other UV-related variables. RESULTS: Seropositivity for at least one beta or gamma HPV was high at 88% (beta HPVs 74%, gamma HPVs 70%), and less in women than men [e.g., PR beta-2 HPV38 = 0.70; 95% confidence interval (CI), 0.56-0.87; any gamma = 0.90; 95% CI, 0.84-0.97]. A high ambient UV level in the 10 years before study enrollment was associated with elevated seroprevalence for genus beta (PRtertile3vs1 any beta = 1.17; 95% CI, 1.07-1.28), and beta-1 to beta-3 species, but not for gamma HPVs. Other UV-related measures had less or no evidence of an association. CONCLUSIONS: Seroprevalence of cutaneous beta HPVs is higher with higher ambient UV exposure in the past 10 years. IMPACT: The observed association between ambient UV in the past 10 years and cutaneous HPVs supports further study of the possible joint role of solar UV and HPV in causing skin cancer.

Evaluation of serum interleukin 17 and zinc levels in recalcitrant viral wart.

BACKGROUND: Warts are benign epithelial proliferations of the skin and mucosa caused by infection with HPV. Low IL-17 levels may contribute in occurrence, maintenance, severity, and recurrence of different types of cutaneous wart that depend mainly on the cell-mediated immunity defect. In a majority of the patients, zinc deficiency was associated with persistent, progressive, or recurrent viral warts. A careful dose of oral zinc sulfate may be helpful in the management of such patients. Zn deficiency negatively affects the Th17 cells. IL 6 induced STAT3 activation during chronic inflammation and Th17 development suppressed by Zn via attenuating this activation critically controls Th17-cell development. OBJECTIVES: To evaluate the role of interleukin 17 and zinc in recalcitrant warts. PATENTS AND METHODS: All studied patients were subjected to history taking and dermatological examination. The evaluation of serum IL-17 level was done by ELISA in 25 recalcitrant wart patients and 25 wart patients. The measurement of serum zinc level was determined by colorimetric methods, using Au 480 Beckman coulter chemistry analyzer. RESULTS: The results revealed a significant decrease in serum IL-17 and zinc levels in recalcitrant wart patients. CONCLUSION: Both IL-17 and zinc deficiency have a role in the pathogenesis of recalcitrant warts through the imbalance of immune system and deficiency of immune cells. There is no significant correlation between serum levels of IL-17 and zinc, suggesting that they have different mechanisms in affecting the immune system.

Efficacy of Intralesional Cryosurgery in the Treatment of Multiple Extragenital Cutaneous Warts: A Randomized Controlled Study.

BACKGROUND: The efficacy of intralesional (IL) cryosurgery in the treatment of cutaneous warts has not been previously studied. OBJECTIVE: To compare the efficacy and safety of IL cryosurgery versus electrosurgery in multiple extragenital warts and investigate their effect on serum interleukin (IL)-12 and interferon-gamma (IFN-γ). MATERIALS AND METHODS: Thirty-one patients were included; 18 received IL cryosurgery, and 13 had electrosurgery. Treatment was performed for the largest or few (2-3) small warts (target) until cleared, leaving the remaining (distant) warts untreated. Clinical response of the target and distant warts and adverse effects were evaluated. Serum IL-12 and IFN-γ levels were assessed before and after treatment. RESULTS: All patients had complete clearing of the treated wart in both groups. IL cryosurgery was well tolerated; infection, ulceration, and recurrence occurred only with electrosurgery. Complete/near-complete resolution of the distant untreated warts was seen in 33.3% versus none of patients in the IL cryosurgery and electrosurgery groups, respectively (p = .003). Furthermore, IL-12 and IFN-γ levels showed a tendency to increase after IL cryosurgery, and their increase correlated with distant wart response. CONCLUSION: Intralesional cryosurgery is effective not only in clearing treated warts but also resolving untreated warts and possibly enhances human papillomavirus-directed immune response.

The Relationship between the Soluble Receptor for Advanced Glycation End Products and Oxidative Stress in Patients with Palmoplantar Warts.

BACKGROUND AND OBJECTIVES: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end products (sRAGE) may act as a protective factor against the deleterious effects of inflammation and oxidative stress, two interconnected processes. However, in HPV infection, the role of sRAGE, constitutively expressed in the skin, has not been investigated in previous studies. MATERIALS AND METHODS: In order to analyze the role of sRAGE in warts, we investigated the link between sRAGE and the inflammatory response on one hand, and the relationship between sRAGE and the total oxidant/antioxidant status (TOS/TAS) on the other hand, in both patients with palmoplantar warts (n = 24) and healthy subjects as controls (n = 28). RESULTS: Compared to the control group, our results showed that patients with warts had lower levels of sRAGE (1036.50 ± 207.60 pg/mL vs. 1215.32 ± 266.12 pg/mL, p < 0.05), higher serum levels of TOS (3.17 ± 0.27 vs. 2.93 ± 0.22 µmol H2O2 Eq/L, p < 0.01), lower serum levels of TAS (1.85 ± 0.12 vs. 2.03 ± 0.14 µmol Trolox Eq/L, p < 0.01) and minor variations of the inflammation parameters (high sensitivity-CRP, interleukin-6, fibrinogen, and erythrocyte sedimentation rate). Moreover, in patients with warts, sRAGE positively correlated with TAS (r = 0.43, p < 0.05), negatively correlated with TOS (r = -0.90, p < 0.01), and there was no significant correlation with inflammation parameters. There were no significant differences regarding the studied parameters between groups when we stratified the patients according to the number of the lesions and disease duration. CONCLUSIONS: Our results suggest that sRAGE acts as a negative regulator of oxidative stress and could represent a mediator involved in the development of warts. However, we consider that the level of sRAGE cannot be used as a biomarker for the severity of warts. To the best of our knowledge, this is the first study to demonstrate that sRAGE could be involved in HPV pathogenesis and represent a marker of oxidative stress in patients with warts.

Intralesional vitamin D3 versus intralesional purified protein derivative in treatment of multiple warts: A comparative clinical and immunological study.

Intralesional (IL) vitamin D3 is an emerging treatment for cutaneous warts. However, its effectiveness and exact mechanism is not fully evaluated. We aimed to compare the efficacy and safety of IL purified protein derivative (PPD) and IL vitamin D3 in multiple warts and to investigate their systemic effect clinically and immunologically. Forty-five patients with multiple extragenital warts were treated with IL-PPD (22 patients) or IL vitamin D3 injection (23 patients) for a maximum of three sessions at 3 week intervals. Decrease in size and number of warts and adverse effects were evaluated. Serum interleukin-12 (IL-12) and interferon-gamma (IFN-γ) levels were measured before and 3 weeks after the last session. Higher clearance rates for all warts were observed with IL-PPD compared to IL vitamin D (59.1% vs. 21.7% complete clearance, p < .001). Significant increase was found in both serum IL-12 and IFN-γ after PPD treatment (p = .034 and p = .04, respectively), but only IFN-γ after vitamin D3 treatment (p = 0.02). Both IL vitamin D3 and PPD showed positive results in treatment of multiple warts. However, PPD showed higher clinical efficacy and more increase in both IL-12 and IFN-γ levels.

Evaluation of oxidative stress in patients with recalcitrant warts.

BACKGROUND: Warts are benign conditions of the skin and mucosa caused by human papilloma viruses (HPV) that affect many people worldwide. OBJECTIVE: The aim of this study was to evaluate OS by TOS/TAS, levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) an indicator of DNA damage, and also protein oxidation levels by determining the dynamic serum thiol/disulphide homeostasis in patients with warts. We also aimed to investigate whether there is a relationship between thiol/disulphide homeostasis, recalcitrance of warts and DNA damage. METHODS: Forty patients of age ≥18 years, having recalcitrant genital and/or non-genital warts that persisted for more than 2 years, 40 patients with warts that persisted for <2 years and 40 healthy controls were enrolled in the study. Blood TAS, TOS, OSI, 8-OHdG and dynamic thiol/disulphide homeostasis were evaluated. RESULTS: Significant differences were detected between the groups in the levels of 8-OHdG, TOS, OSI, total thiol, native thiol, reduced thiol, as well as native thiol/total thiol ratio, disulphide/total thiol ratio and disulphide/native thiol ratio. Compared with the controls, patients with recalcitrant warts had significantly higher levels of 8-OHdG, TOS and OSI levels. Total thiol and native thiol levels were significantly lower in patients with recalcitrant warts compared with patients with warts that persisted for <2 years. Disulphide levels were significantly higher in the latter group of patients compared with patients with recalcitrant warts and controls. Native thiol/total thiol ratio was significantly higher in both patient groups compared with controls whereas disulphide/total thiol and disulphide/native thiol ratios were significantly lower in both patient groups than in controls. CONCLUSION: Our findings suggest that impairment of thiol disulphide homeostasis in patients with recalcitrant warts may lead to increased OS and DNA damage. Thus, antioxidant administration with thiol containing proteins may help in the regression of warts and thereby prevent carcinogenesis.

Serum retinol-binding protein: a novel biomarker for recalcitrant cutaneous warts.

BACKGROUND: Cutaneous viral warts are benign epidermal proliferations caused by human papillomaviruses (HPVs). Despite treatment, a significant proportion of warts fail to resolve, becoming recalcitrant. Vitamin A (retinol) may disrupt the interplay of HPV replication and epithelial cell differentiation, allowing normal tissue to replace warts. Circulating retinol-binding protein (RBP) concentrations highly correlate with retinol levels. AIM: We aimed at evaluation of serum RBP level in patients with recalcitrant cutaneous warts in order to assess its correlation with disease pathogenesis. METHODS: Serum RBP level was measured by an ELISA technique in 50 patients with recalcitrant cutaneous warts and 30 apparently healthy controls. RESULTS: Serum RBP level was significantly lower in patients with recalcitrant warts than the control group (P < 0.001). However, it did not differ regarding different clinical parameters in studied patients (P > 0.05 each). RBP is a reliable biomarker for significant early detection and discrimination between patients and healthy controls (P < 0.001) at a cutoff value ≤1034.6 µg/ml, with sensitivity and specificity (100% each). CONCLUSION: Our results revealed that low serum RBP as a relatively cheap biomarker with high specificity and sensitivity is a reliable indicator of vitamin A (retinol) deficiency that may play a role in the pathogenesis of recalcitrant cutaneous warts among our studied patients.

Peripheral blood toll-like receptor 4 correlates response to candida immunotherapy of warts.

Human papilloma virus infection may be self-limiting; however, some cases may spread. There are no factors predicting the prognosis of such infections. The present study aimed to evaluate the significance of TLR4 expression in predicting the response of warts to candida immunotherapy. A total of 60 patients with different types of warts were included in the present study. A total volume of 2 ml venous blood was collected and real-time polymerase chain reaction was used to determine expression of TLR4. Patients were subjected to intralesional injection of Candida antigen into the largest wart at 2-week intervals until complete clearance or for a maximum of six sessions. Of the total 58 patients available for analysis of study results, 44 patients (75.9%) showed complete resolution with better response in younger ages. The TLR4 expression in patients with complete and partial response was significantly higher than that in patients who had no response (p = .006). Among our patients, 48.3% showed no side effects, 44.8% showed local reactions, and 6.9% showed systemic side effects. Only four patients showed recurrence after 6 months. Using receiver operating characteristic curve analysis, at cutoff of expression level >12 is accompanied by 100% specificity of TLR4 in predicting treatment response to candida immunotherapy. Candida immunotherapy is an effective warts treatment, especially in young patients. Higher PMBC TLR4 levels can predict response to candida immunotherapy.

Possible role of interleukin-17 and macrophage migration inhibitory factor in cutaneous warts.

BACKGROUND/OBJECTIVES: Cutaneous warts (CW), or verrucae, are benign proliferation of skin that result from infection with human papilloma viruses. Cellular immune reactivity plays a significant role in wart regression. The aim of this study was to elucidate the cellular immune status of patients with CW through measurements of their serum levels of interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF,) and, identify the possible role of IL-17 and MIF in CW. We assessed serum IL-17 and MIF levels in patients with different forms of CW and compare the results with controls. PATIENT AND METHODS: Serum levels of IL-17 and MIF were measured using commercially available ELISA assay kits in 60 patients with CW and 20 healthy controls. RESULTS: Serum levels of IL-17 and MIF were significantly lower in patients with CW when compared with the controls (P-value <.01, <.05, respectively). There was nonsignificant correlation between IL-17 and MIF. CONCLUSION: Low IL-17 and MIF levels may have a contributory role in occurrence, maintenance, severity, and recurrence of different types of CW which depend mainly on the defect of cell-mediated immunity. This may shed new light on nontraditional strategies for the future medical treatments of CW through regulation of IL-17 and MIF.

Evaluation of TNF-α serum level in patients with recalcitrant multiple common warts, treated by lipid garlic extract.

No universal consensus about optimal modality for treating the recalcitrant multiple common warts (RMCW). The objective of the study was to evaluate the immunological mechanisms and clinical therapeutic effect of using lipid garlic extract (LGE) in the treatment of RMCW. The study included 50 patients with RMCW. They were randomly assigned into two groups: the first group (25 patients) received LGE, and the second group (25 patients) received saline as a control group. In both groups, treatments were made to single lesions, or largest wart in case of multiple lesions, until complete clearance of lesions or for a maximum of 4 weeks. Blood serum was taken at pre-study and at the fourth week to measure tumor necrosis factor alpha (TNF-α) level. A significant difference was found between the therapeutic responses of RMCW to LGE antigen and saline control group (p < 0.001). In the LGE group, complete response was achieved in 96% of patients presenting with RMCW. There was a statistically nonsignificant increase in TNF-α of LGE group versus saline group. No recurrence was observed in the LGE group. LGE as an immunotherapy is an inexpensive, effective, and safe modality with good cure rates for treatment of RMCWs, when other topical or physical therapies have failed.

Evaluation of IL-12 serum level in patients with recalcitrant multiple common warts, treated by intralesional tuberculin antigen.

BACKGROUND: No universal consensus about optimal modality for treating the recalcitrant multiple common warts (RMCW). OBJECTIVE: To evaluate the immunological mechanisms and clinical therapeutic effect of using of intralesional purified protein derivative (PPD) in the treatment of RMCW. METHODS: The study included 40 patients with RMCW. They were randomly assigned to 2 groups: first group (20 patients) received intralesional PPD antigen, and second group (20 patients) received intralesional saline as a control group. In both groups, injections were made into single lesions, or largest wart in case of multiple lesions, at weekly intervals, until complete clearance or for a maximum of six treatments. Blood serum was taken at pre-study and at week 6 to measure IL-12 level. RESULTS: A significant difference was found between the therapeutic responses of RMCW to PPD antigen and saline control group (p < 0.001). In the PPD group, complete response was achieved in 75% after 5.8 ± 0.7 sessions' patients presenting with RMCW. There was a statistically significant increase in IL-12 of PPD group versus saline group. No recurrence was observed in the PPD group. CONCLUSION: Intralesional immunotherapy by PPD antigen is an effective and a safe treatment for RMCW in previously immunized patients.

Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm² applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm² were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC0₋24 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC0₋24. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.

The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome.

WHIM syndrome is a rare congenital immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia because of impaired egress from the BM); most patients also have severe panleukopenia. Because WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that result in increased agonist-dependent signaling, we hypothesized that the CXCR4 antagonist plerixafor (Mozobil [Genyzme Corporation], AMD3100), might be an effective treatment. To test this, we enrolled 3 unrelated adult patients with the most common WHIM mutation, CXCR4(R334X), in a phase 1 dose-escalation study. Plerixafor increased absolute lymphocyte, monocyte, and neutrophil counts in blood to normal without significant side effects in all 3 patients. Peak responses occurred at 3-12 hours after injection and waned by 24 hours after injection which tracked the drug's pharmacokinetics. All 3 cell types increased in a dose-dependent manner with the rank order of responsiveness absolute lymphocyte > monocyte > neutrophil. These data provide the first pharmacologic evidence that panleukopenia in WHIM syndrome is caused by CXCL12-CXCR4 signaling-dependent leukocyte sequestration, and support continued study of plerixafor as mechanism-based therapy in this disease. This study is registered at http://www.clinicaltrials.gov as NCT00967785.

The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome.

Mutations in CXCR4 cause severe leukopenia in myelokathexis or WHIM syndrome. Plerixafor inhibits binding of CXCR4 to its ligand CXCL12. We investigated the effects of plerixafor (0.04 to 0.24 mg/kg) administered at 2-4 day intervals in 6 patients. Outcome measures were the patients' complete blood cell counts, CD34(+) cell counts and lymphocyte subtypes compared with 5 normal subjects similarly treated with plerixafor. All patients showed prompt leukocytosis with maximum blood neutrophils and lymphocytes at 6-12 hours. Blood neutrophils peaked at 6-12 hours, increasing from a mean baseline of 0.4 ± 0.1 × 109/L, to mean peak of 4.5 ± 0.78 × 109/L. Lymphocytes also increased; the greatest increase was in B cells (CD19(+) cells), a > 40-fold increase over baseline at the 0.08 mg/kg dose. None of the patients experienced any significant adverse effects. Plerixafor is a promising therapy for this condition.