Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review.

Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence. The aim of this review was to appraise the existing evidence regarding the impact of exercise on surface markers of cellular immunosenescence in either young and old humans or animals. PubMed and Web of Science were systematically screened, and 28 relevant articles in humans or animals were retrieved. Most of the intervention studies demonstrated that an acute bout of exercise induced increases in senescent, naïve, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic lymphocytes in peripheral blood. As regards long-term effects, exercise induced increased levels of T-lymphocytes expressing CD28+ in both young and elderly subjects. Few studies found an increase in natural killer cell activity following a period of training. We can conclude that exercise has considerable effects on markers of cellular aspects of the immune system. However, very few studies have been conducted so far to investigate the effects of exercise on markers of cellular immunosenescence in elderly persons. Implications for immunosenescence need further investigation.

Shortcomings in the application of multicolour flow cytometry in lymphocyte subsets enumeration.

The lymphoid system is composed of numerous phenotypically distinct subsets of cells, each of which has a unique role in the effectiveness of an immune response. To distinguish specifically between these subsets, it is mandatory to detect simultaneously different cell surface antigens. This became feasible by the development of multicolour flow cytometric technologies. With these techniques, researchers now have the opportunity to study individual cells in far greater detail than previously possible. However, proper data analysis, interpretation and presentation of results will require a high level of understanding of the intricacies of the technology and the inherent limitations of the acquired data. The present report is intended to contribute to the better understanding of how the flow cytometer operates. This report may help new and inexperienced users to work appropriately with the flow cytometer.

Restaging the mediastinum in non-small cell lung cancer after induction therapy: non-invasive versus invasive procedures.

OBJECTIVE: Nodal status after induction therapy in patients with stage III non-small cell lung cancer (NSCLC) is an independent prognostic factor for survival. Prognosis is poor in patients with persisting mediastinal lymph node involvement. METHODS: From February 2000 to September 2007, restaging for NSCLC was performed in 25 patients (23 men, 2 women) by computed tomography (CT), positron emission tomography (PET) as well as repeat mediastinoscopy. Initial proof of N2 or N3 disease was obtained by mediastinoscopy. RESULTS: The non-invasive restaging modalities CT and PET had a rather low accuracy of 64% and 72%, respectively. Repeat mediastinoscopy performed better with an accuracy of 84%. CONCLUSION: Histological proof of mediastinal involvement after induction therapy in NSCLC is necessary to select those patients who will benefit from surgical resection. When a first mediastinoscopy has been performed to obtain pathological proof of N2 or N3 disease, repeat mediastinoscopy proves to be more accurate than CT or PET scanning for mediastinal restaging.

Different indications for repeat mediastinoscopy: single institution experience of 79 cases.

AIM: Different indications exist for repeat mediastinoscopy or remediastinoscopy (reMS). Presently, it is a valuable restaging tool in non-small cell lung cancer (NSCLC). Not only does it provide pathological evidence of mediastinal downstaging, it also selects those patients who will benefit from a subsequent surgical resection and determines prognosis. However, other indications for reMS exist. The authors reviewed their overall experience with reMS. METHODS: From June 1994 until September 2007, 79 reMS were performed in 75 patients (65 men and 10 women). Mean age was 67.4 years (range 35 to 85 years). RESULTS: ReMS was performed after induction therapy in 54 cases (68.4%), for recurrent lung cancer in 7 cases (8.9%), metachronous second primary lung cancer in 2 cases (2.5%), for lung cancer occurring after an unrelated disease such as sarcoidosis in 1 case (1.2%), for an inadequate first procedure in 8 cases (10.1%) and for a non-malignant disease such as sarcoidosis or lymphoma in 7 cases (8.9%). ReMS was technically feasible in all patients. There was no mortality. One hemorrhage was encountered from a bronchial artery during reMS which was controlled by packing and one tear in the bronchial wall which was treated conservatively. In patients with lung cancer (71 patients), reMS was positive in 29 cases (40.8%). ReMS provided a definitive diagnosis in 3 patients with sarcoidosis and in one patient with lymphoma . CONCLUSIONS: Although mostly performed as a restaging procedure after induction therapy in non-small cell lung cancer, reMS can also safely be performed for other indications providing pathological evidence of mediastinal involvement.

[Stage III NSCLC. The surgeon's role in exploration and treatment]. / La place du chirurgien dans l'exploration et le traitement.

The role of surgery in stage IIIA non-small cell lung cancer (NSCLC) remains controversial. Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive, invasive and alternative or minimally invasive techniques. Remediastinoscopy provides pathological evidence of response after induction therapy. Stage IIIA-N2 NSCLC represents a heterogeneous spectrum of locally advanced disease and different subsets exist. When N2 disease is discovered during thoracotomy a resection should be performed if this can be complete. Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy. In two large, recently completed, phase III trials there was no difference in overall survival between the surgical and radiotherapy arm. Surgical resection may be recommended in those patients with proven mediastinal downstaging after induction therapy who can preferentially be treated by lobectomy. Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy although the precise treatment scheme has not been determined yet. Also, stage IIIB is mostly treated by concurrent or sequential chemoradiotherapy. Surgery is rarely indicated in T4N0-1 disease unless a complete resection can be obtained, in some selected cases after induction therapy.

Paravertebral schwannoma with high uptake of fluorodeoxyglucose on positron emission tomography.

A paravertebral mass was discovered in a 27-year-old woman, while investigating a painful shoulder and arm. CT, MRI and fine needle aspiration cytology (FNAC) pointed in the direction of a benign mass, but positron emission tomography (PET) showed a high uptake of [(18)F]fluorodeoxyglucose (FDG), which was indicative of a malignant lesion. Pathological analysis of the thoracoscopically resected tumour gave us the final diagnosis of a benign schwannoma. This report demonstrates that a high uptake of FDG in a non-malignant mediastinal tumour is possible.

Clinical experience with the N-shaped ileal neobladder: assessment of complications, voiding patterns, and quality of life in our series of 58 patients.

PURPOSE: The purpose of this retrospective study was to assess complications, voiding patterns, and quality of life in patients with an orthotopic bladder substitution, using an N-shaped ileal neobladder. MATERIALS AND METHODS: Between May 1996 and December 2002, 58 patients (52 men and 6 women) underwent an orthotopic ileal neobladder reconstruction after radical cystectomy. The mean age was 47 for the female and 60 for the male patients. In all patients an N-shaped ileal pouch was constructed. This pouch has not yet been described in the literature before. All procedures were performed by the same surgeon (HVP) and the mean follow-up was 38 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), and as pouch-related and non-pouch-related. The patients took part in a pelvic floor re-education programme for as long as they were incontinent. All patients completed a retrospective Quality of Life questionnaire, based on the QLQ-C30 questionnaire, which was validated by the EORTC's Study Group on Quality of Life. RESULTS: In 38% of the patients, early complications occurred, whereas 48% had late complications. The most frequent early complications were diarrhea (24%) and pyelonephritis (9%). Diarrhea was again the most frequently mentioned non-pouch-related complication (19%). The most frequently observed pouch-related late complication was ileo-urethral stenosis. This occurred in five patients. All of these 5 patients were re-operated using a minimally invasive approach. Daytime continence was achieved in 95% of patients and nighttime continence in 66%. Hyper-continence with subsequent need for CISC was observed in 5 out of 6 women (83%) and 0 out of 52 men (0%). The retrospective QoL questionnaire learned that the impact of bladder removal and orthotopic bladder substitution has acceptable impact on patient's everyday life. Diarrhea was mentioned as being the most discomforting complication by most of the patients. CONCLUSIONS: We describe a modified orthotopic ileal neobladder: the ileal N-pouch. The functional results with this pouch are good. Complication rates and QoL are comparable with the larger series published by other authors, using different ileal neobladder reconstructions.

Characterisation of pleural inflammation occurring after primary spontaneous pneumothorax.

The aim of this study was to examine the inflammatory reaction occurring in the pleural space of patients suffering from primary spontaneous pneumothorax (PSP) using pleural lavage, which was performed in patients with PSP and in healthy control subjects (essential hyperhidrosis patients undergoing thoracoscopy for sympathicolysis treatment). Cellular and solute composition of lavage fluid, peripheral blood and parietal pleural biopsies were analysed. PSP lavage fluid showed an increase in all differentiated leucocytes, but most strikingly eosinophils and neutrophils. In the blood of patients with PSP, the total number of leucocytes and the absolute number of eosinophils, neutrophils and monocytes were also significantly increased. The time in which air was present in the pleural space was positively correlated with the increase of eosinophils in lavage fluid, parietal pleura and blood. Eosinophilic cationic protein was elevated after PSP and strongly correlated with the absolute number of lavage eosinophils. Chemo and cytokine analysis in lavage fluid showed differences in concentrations of interleukin (IL)-5, IL-6, IL-8, IL-12p40, tumour necrosis factor-alpha and RANTES, but not of eotaxin. Surprisingly, high levels of lipopolysaccharide binding protein were also measured. Primary spontaneous pnumothorax is associated with a substantial pleural inflammatory reaction. The authors hypothesise that mechanical stretch factors, lipopolysaccharide binding protein/lipopolysaccharide complexes or other environmental components trigger pleural inflammation after primary spontaneous pnumothorax.

Growth factor receptor profile of CD34 cells in normal bone marrow, cord blood and mobilized peripheral blood.

Growth factors regulate the proliferation and differentiation of hemopoietic cells. Their effect on hemopoietic precursors differs according to the ontogenic source of the cells. Cord blood and mobilized blood CD34(+) cells have a higher sensitivity for growth factors than bone marrow CD34(+) cells. This could be due to a higher expression of growth factor receptors. Therefore, we examined the expression of receptors for stem cell factor (SCF), interleukin-6 (IL-6), IL-3, granulocyte colony-stimulating factor (G-CSF) and IL-7 on the CD34(+) cells of cord blood, mobilized peripheral blood and bone marrow. The receptors were detected with monoclonal antibodies and flow cytometry. The majority of the CD34(+) cells in bone marrow clearly expressed SCFR; they showed a moderate positivity for IL-3Ralpha and a weak staining for G-CSFR and IL-6 Ralpha. Less than 10% of the cells were IL-7R positive. Cord blood CD34(+) cells showed a higher expression of SCFR and a lower positivity for G-CSFR and IL-6Ralpha. Mobilized blood CD34(+) cells showed a lower expression of SCFR and G-CSFR, and a higher positivity for IL-3Ralpha. This was not solely due to the presence of more myeloid precursors in mobilized blood, as the growth factor receptor profile did not correspond to that of early or late myeloid CD34(+) precursors in normal bone marrow. Changes induced by the mobilization procedure occurred as well. In conclusion, the higher sensitivity for growth factors of hemopoietic precursors in cord blood and mobilized blood cannot be explained by a general increase of the growth factor receptor expression on the CD34(+) cells.

Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation.

Serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha were frequently measured during the first 30 days after allogeneic bone marrow transplantation (BMT) in 84 consecutive adult patients. Major transplant-related complications (MTCs) occurred in 33% of cases and included veno-occlusive liver disease, idiopathic pneumonia syndrome, severe endothelial leakage syndrome and >grade II acute graft-versus-host disease. Compared with patients having minor complications, those with MTCs developed higher levels at times of maximal clinical signs (all cytokines, P<0.001), between days 0-5 post-BMT (IL-6 and IL-8, P<0.05) and days 6-10 (L-6, P<0.001; IL-8 and TNF, P<0.01) post-BMT. We could not discriminate patterns of cytokine release that were specific for any subtype of MTC. Higher levels of IL-8 during days 0-5 were associated (P=0.044) with early (<40 days) death. Multivariate analysis including patient and transplant characteristics as well as post-BMT levels of C-reactive protein showed that high average levels of one or more of the cytokines within the first 10 days post-BMT were independently associated with MTC (Odd's ratio: 2.3 [1.2-4.5], P=0.011). This study shows that systemic release of proinflammatory cytokines contributes to the development of MTC and provides a rationale for pre-emptive anti-inflammatory treatment in selected patients.

Differential cytology of bronchoalveolar lavage fluid in asthmatic children.

Although asthma usually begins in childhood, limited information is available as to the inflammatory reaction of asthmatic children compared to adults and the influence of age. We investigated the cytology of bronchoalveolar lavage fluid (BALF) in 39 newly diagnosed wheezy children (minimum of 3 wheezing episodes during last 6 months): 21 allergic and 18 nonallergic subjects. None had received antiinflammatory treatment. Bronchoalveolar lavage (BAL) was performed, instilling 0.5 ml.kg(-1) body weight of warmed saline in 4 successive fractions. The first 2 aliquots (BALF 1) were pooled for microbiology and cytology, and the last 2 (BALF 2) for cytology only. Recovery correlated inversely with age, the most significant being for BALF 2 (r = -0.52, P = 0.001). Children under 2 years of age had larger amounts of ciliated columnar and goblet cells (P = 0.0074). Other cell types did not show age dependency. Differential cytology was characterized by a high number of creola bodies, bronchial epithelial cells (M = 68 x 10(3).ml(-1), R = 5-349), and neutrophils (M = 92 x 10(3).ml(-1), R = 0-1,257). Eosinophils were the only cells distinguishing allergic from nonallergic subjects (P = 0.003). The 16 children with positive microbiology had more neutrophils than the noninfected (P = 0.008), the latter still having more neutrophils than found in adults. These data suggest a limited age dependency in BALF cytology. Differential cytology in BALF might be helpful in differentiating asthma in children. Neutrophil inflammation might be more important than in adults.

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation.

We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15-50 years) transplanted in our unit. Major transplant-related complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0-5) and >100 mg/l between days 6 and 10 (CRP day 6-10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P= 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6-10 >100 mg/l) vs 17% (CRP day 6-10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5-10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive anti-inflammatory treatment.

Plasma D-dimer concentrations in different clinical conditions.

D-dimers (DD), specific degradation products of crosslinked fibrin, are markers for activation of plasma coagulation and/or fibrinolysis. DD results below the cut-off level are proven to be useful to rule out the probable diagnosis of deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Our objective was to demonstrate that positive DD occur in many diseases and certain physiological conditions as high age and pregnancy and to look for gradations in positivity between different pathological conditions. We wanted to investigate the request attitude of our clinicians concerning DD. Positive DD results still confuse some physicians. Retrospectively, we examined medical records of 574 consecutive patients, in whom plasma DD were measured in daily routine. Both outpatients (n = 423) and inpatients (n = 151) were included. We noted their clinically predominant disease. Measurement of DD concentration is too often requested by clinicians, in any medical condition, and is not always clinically relevant. The relation of a positive result and the clinical problem is sometimes not understood. Overall, we found 64% DD positivity with a median concentration of 775 micrograms/L. We found elevated DD concentrations in various clinical conditions.

The impact of partial T cell depletion on overall transplant-related toxicity, graft function and survival after HLA-identical allogeneic bone marrow transplantation in standard risk adult patients with leukemia.

In this single-center study, a consecutive cohort of 59 adult patients transplanted with HLA-identical bone marrow and receiving graft-versus-host disease (GVHD) prophylaxis with either standard cyclosporine/methotrexate (n = 33) or partial T cell depletion (E-rosetting) (TCD, n = 26 were analyzed). Only patients with chronic myeloid leukemia in first chronic phase or acute leukemia/myelodysplasia in first or second remission were included. Except for age (median 28 vs 42 years), both groups were comparable in terms of diagnosis, conditioning regimen and growth factor support. TCD significantly reduced >grade II acute GVHD (0 vs 24%, P = 0.02), chronic GVHD (8.5 vs 45%, P = 0.007) and other major bone marrow transplant (BMT)-related complications (4 vs 36%, P = 0.005). TCD decreased overall transplant-related mortality (11.5 vs 36%, P = 0.04). In the TCD group faster neutrophil (13 vs 22 days, P = 0.02) and platelet recoveries (18 vs 26 days, P < 0.001) were noted. The relapse risk was higher after TCD (57.5 vs 21.5%, P = 0.04). Overall survival probability at 10 years was identical in both groups (54 vs 53.5%, P = 0.33). We found a relationship between the number of T cells in the graft and the occurrence of major complications (P < 0.001) and relapse (P = 0.03). This comparative analysis shows that graft-derived T cells have a major role in overall BMT-related toxicity and that partial TCD is an acceptable approach in terms of survival for patients between 40 and 50 years of age.

Growth factor receptor profile of CD34+ cells in AML and B-lineage ALL and in their normal bone marrow counterparts.

Leukaemic cells show a low clonogenic activity and a heterogeneous proliferative response to growth factors. We investigated whether this could be due to an altered expression of growth factor receptors on the leukaemic precursors. Receptors for G-CSF, stem cell factor (SCF), IL-3, IL-6 and IL-7 were detected on CD34+ cells in AML and B-lineage ALL with monoclonal antibodies and flow cytometry. The expression was compared with that on myeloid and B-lymphoid CD34+ cells in normal bone marrow. Leukaemic CD34+ cells expressed the same receptors as their normal counterparts. AML and B-lineage ALL could be distinguished by the growth factor receptor profile of their CD34+ cells. SCFR, G-CSFR and IL-6Ralpha were found in AML, IL-7R in B-lineage ALL and IL-3Ralpha in both. IL-3Ralpha was upregulated in AML and B-lineage ALL CD34+ cells, while samples with low or high expression were present for the other receptors. This variable expression could correlate with the heterogeneous response of leukaemic cells to growth factors. Functional studies on isolated CD34+ cells are needed to investigate this further.

Clonally related IgA- and IgE-secreting plasma cells in a myeloma patient.

OBJECTIVES: The purpose of this work was to study the clonal relationship between the cells that secrete monoclonal proteins in an IgA/ IgE double multiple myeloma patient. Double monoclonal gammopathy is a rare condition in which two types of monoclonal proteins can be found in the serum and/or urine of patients with multiple myeloma or gammopathy of undetermined significance. The study of the relationship between the cells expressing the different monoclonal proteins may provide insight in the pathogenesis of these disorders. METHODS: The clonal relationship of the two tumoral plasma cell populations was examined by immunophenotyping and sequence analysis of the variable regions of the immunoglobulin heavy chain genes. Both immunoglobulin sequences were isolated from the bone marrow using a polymerase chain reaction (PCR)-based cloning strategy. Rare isotype-switch variants were detected by a myeloma-specific PCR in combination with different isotype-specific primers. An in vitro culture system, based on the activation of the CD40 molecule on the B cell, was used in order to isolate and expand myeloma-related B cells from peripheral blood that could possibly be regarded as myeloma precursor cells. RESULTS: The variable parts of the immunoglobulin heavy chains linked to either Calpha or Cepsilon were exactly the same, including the same somatic mutations. From the in vitro CD40 cultures B cells could be isolated that either expressed IgA or IgE with exactly the same variable immunoglobulin part as the myeloma clone. No pre-switched IgM myeloma-related B cells could be found. CONCLUSION: Both cell populations in this IgA/IgE myeloma patient shared a common clonal origin. No evidence for a pre-switched IgM precursor myeloma cell was found in this patient.

Volume and cellular content of normal pleural fluid in humans examined by pleural lavage.

Currently, no reliable data are available on the volume or on the cellular content of pleural fluid in normal humans. In analogy with bronchoalveolar lavage (a technique enabling retrieval of small volumes of epithelial lining fluid from the lung), we developed a pleural lavage (PL) technique consisting of injection and retrieval of 150 ml of saline into the right pleural space, performed during a thoracoscopic sympathicolysis procedure in otherwise healthy subjects suffering from essential hyperhidrosis. With urea used as an endogenous marker of dilution, measured mean right-sided pleural fluid volume was 8.4 +/- 4.3 ml. In a subgroup of subjects, we confirmed that right- and left-sided pleural fluid volumes were similar. Expressed per kilogram of body mass, total pleural fluid volume in normal, nonsmoking humans is 0.26 +/- 0.1 ml/kg. Total cell count in the PL fluid of nonsmoking normal subjects yielded a median of 91 x 10(3) white blood cells (WBC) per milliliter of lavage fluid (interquartile range [IR] = 124 x 10(3) cells/ml). Taking into account a measured dilution factor of 18.86, the total WBC count in the original pleural fluid was 1,716 x 10(3) cells/ml. Differential cell counts yielded a predominance of macrophages (median: 75%; IR: 16%) and lymphocytes (median: 23%; IR: 18%). Mesothelial cells (median: 1%; IR: 2%), neutrophils (median: 0%; IR: 1%), and eosinophils (median: 0%; IR: 0%) were only marginally present. There were no significant differences between males and females or between right- and left-sided pleural fluid in total and differential cell counts. In contrast, in smokers a small but statistically significant increase in pleural fluid neutrophils (median: 1%; IR: 2%; p < 0.015) was observed. In conclusion, PL performed during thoracoscopy for sympathicolysis allowed for the first time determination of the volume and of the total and differential cell contents of the pleural fluid present in normal human pleura.

Different expression of adhesion molecules on CD34+ cells in AML and B-lineage ALL and their normal bone marrow counterparts.

The expression of adhesion molecules on CD34+ cells in acute myeloid leukemia (AML) and B-lineage acute lymphoblastic leukemia (B-lineage ALL) was compared with that on the myeloid and B-lymphoid CD34+ cells in normal bone marrow. Bone marrow aspirates of 10 patients with AML, 8 patients with B-lineage ALL and of 6 healthy volunteers were examined. The phenotype of the CD34+ cells was determined with a double immunofluorescence method and flow cytometry. CD34+ cells in AML and B-lineage ALL showed a lower expression of VLA-2 and VLA-3 and a higher expression of ICAM-1 and LFA-3 than their normal bone marrow counterparts. AML CD34+ cells had less L-selectin but more VLA-5 on their surface membrane than normal myeloid CD34+ cells. B-lineage ALL CD34+ cells showed an overexpression of LFA-3. In individual patients deficiencies or over-expression of the beta1 integrin chain, VLA-4, PECAM-1 or HCAM also occurred. An abnormal adhesive capacity of the leukemic cells may influence their proliferation, their localisation and apoptosis. An aberrant expression of adhesion molecules may be used for the detection of minimal residual leukemia in these patients.

Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial.

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34(+) cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 x 10(6) CD34(+) cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m(2)) and either SCF (20 micrograms/kg/d) combined with filgrastim (5 micrograms/kg/d) or filgrastim alone (5 micrograms/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 micrograms/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 x 10(6) CD34(+) cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P =.008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 x 10(6) CD34(+) cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34(+) cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 x 10(6)/kg, P =.003) and all leukaphereses (12.4 v 8.2 x 10(6)/kg, P =.007). Total colony-forming unit-granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34(+) cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34(+) cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 x 10(6) CD34(+) cells/kg.