Impact of intensive PBSC mobilization therapy on outcomes following auto-SCT for non-Hodgkin's lymphoma

The best method to mobilize PBSCs in patients with non-Hodgkin's Lymphoma (NHL) is uncertain. We hypothesized that PBSC mobilization using an intensive chemotherapy regimen would improve outcomes after autologous hematopoietic stem cell transplantation (ASCT) in NHL patients at high risk for relapse. Fifty NHL patients were prospectively allocated to intense mobilization with high-dose etoposide plus either high-dose cytarabine or CY if they were 'high risk' for relapse, whereas 30 patients were allocated to nonintense mobilization with CY if they were 'standard risk' (all patients, +/-rituximab). All intensely mobilized patients were hospitalized compared with one-third of nonintensely mobilized patients. The EFS after ASCT was the same between the two groups, but overall survival (OS) was better for intensely mobilized patients (<0.01), including the diffuse large B-cell subgroup (P<0.04). We conclude that the intense mobilization of PBSCs in patients with NHL is more efficient than nonintense mobilization, but with greater toxicity. The equalization of EFS and superiority of OS in patients intensely mobilized to those nonintensely mobilized suggests that a treatment strategy using intensive chemotherapy for mobilization may be improving NHL outcomes after ASCT.     

Comparison of monocyte-dependent T cell inhibitory activity in GM-CSF vs G-CSF mobilized PSC products

This study compares the immune properties of peripheral blood stem cell (PSC) products mobilized with different hematopoietic growth factors (HGFs) as well as apheresis products and peripheral blood leukocytes (PBL) from normal individuals. We found that monocytes in mobilized PSC products appear to inhibit T cell function independent of whether granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was used for mobilization. In addition, the GF used to mobilize the stem cell product may be less important to the CD4:CD8 ratio than the extent of prior chemotherapy, as we found an inverse correlation between chemotherapy and the CD4:CD8 ratio. In other observations, all apheresis products, whether mobilized or unmobilized, contained significantly more monocytes compared to normal PBL. The mononuclear cells (MNC) from G-CSF or GM-CSF mobilized PSC products had a similar T cell phytohemagglutinin (PHA) mitogenic response that was significantly lower (P = 0.001 and P = 0.005, respectively) than non-mobilized apheresis products. We also examined the T cell inhibitor (TI) activity of the MNC from the PSC products for allogeneic lymphocyte proliferation and found that PSC products significantly reduced the proliferation of allogeneic PBL to PHA. A significant correlation (P = 0.001, r = 0.517) between the frequency of monocytes and TI activity also was observed.     

Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization.

High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1-4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 x 10(6)/kg (range 2.2-12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 x 10(6) CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+ cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/microl vs 4.7/microl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.     

Autologous stem cell transplantation for HIV-associated lymphoma.

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)- associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV(-)) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 x 10(6) CD34(+) cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.     

Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients

Peripheral blood progenitor cells (PBPC) can be mobilized using chemotherapy and granulocyte colony-stimulating factor (G-CSF). We and others previously reported a correlation of steady-state PBPC counts and the PBPC yield during mobilization in a small group of patients. Here we present data on 100 patients (patients: 25 non-Hodgkin's lymphoma (NHL), five Hodgkin's disease, 35 multiple myeloma (MM), 35 solid tumour) which enabled a detailed analysis of determinants of steady-state PBPC levels and of mobilization efficiency in patient subgroups. Previous irradiation (P = 0.0034) or previous chemotherapy in patients with haematological malignancies (P = 0.0062) led to a depletion of steady-state PB CD34+ cells. A correlation analysis showed steady-state PB CD34+ cells (all patients: r = 0.52, P < 0.0001; NHL patients, r = 0.69, P = 0.0003; MM patients: r = 0.66, P = 0.0001) and PB colony-forming cells can reliably assess the CD34+ cell yield in mobilized PB. In patients with solid tumour a similar trend was observed in mobilization after the first chemotherapy cycle (r = 0.51, P = 0.05) but not if mobilization occurred after the second or further cycle of a sequential dose-intensified G-CSF-supported chemotherapy regimen, when premobilization CD34+ counts were 18-fold elevated (P = 0.004). When the patients with MM (r = 0.63, P = 0.0008) or with NHL (r = 0.65, P = 0.006) were analysed separately, a highly significant correlation of the steady-state PB CD34+ cell count to the mean leukapheresis CD34+ cell yield was found, whereas no correlation was observed for patients with a solid tumour. For patients with haematological malignancies estimates could be calculated which, at a specific steady-state PB CD34+ cell count, could predict with a 95% probability a defined minimum progenitor cell yield. These results enable recognition of patients who mobilize PBPC poorly and may assist selection of patients for novel mobilization regimens.     

Patients mobilizing large numbers of CD34+ cells ('super mobilizers') have improved survival in autologous stem cell transplantation for lymphoid malignancies

The cellular composition of an autologous graft may influence autologous stem cell transplantation (ASCT) outcome. Etoposide (VP) plus filgrastim (G) frequently mobilizes high numbers of CD34+ cells for autologous transplantation. We investigated whether patients collecting high numbers of CD34+ cells ('super mobilizers') have a better outcome than other patients. We reviewed 350 consecutive adult patients with NHL or Hodgkin's lymphoma receiving an ASCT from January 1994 to December 2005, mobilized with VP+G. Super mobilizers were defined as collecting a minimum of 8 x 10(6) CD34+ cells/kg. Two hundred and three patients were super mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Super mobilizers were younger and more likely to have received two or fewer prior chemotherapy regimens (80 versus 63%, P<0.001). Median CD34+ cell dose for the super mobilizing group was 13.7 x 10(6) versus 4.4 x 10(6)/kg in the standard collecting group. The super mobilizer group had a superior overall survival (P=0.006). In multivariable analysis, favorable disease status and younger age at transplant, and super mobilization were associated with improved survival. We conclude that patients had an improved ASCT outcome if large numbers of CD34+ cells were mobilized and infused. The explanation for this observation is unknown.     

Feasibility and toxicity of high-dose chemotherapy supported by peripheral blood stem cell transplantation in elderly patients (>/=60 years) with non-Hodgkin's lymphoma: comparison with patients <60 years treated within the same protocol

Limited data are available concerning feasibility and toxicity of progenitor cell mobilization and high-dose therapy (HDT) supported by peripheral blood stem cell transplantation (PBSCT) in elderly patients (>/=60 years) with non-Hodgkin's lymphoma (NHL). From 1995 to 1999, 17 elderly NHL patients (median age 63 years, range 60-70) entered our HDT program and were mobilized with CY (4 g/m2) followed by G-CSF. Mobilization was successful in 13 patients, who then received BEAM or BEAC followed by PBSCT. The feasibility and toxicity of progenitor cell mobilization and HDT in the elderly patients were compared with experiences in 62 NHL patients <60 years (median 46 years, range 16-59), who received the same mobilization protocol and of whom 48 patients received HDT supported by PBSCT. No significant differences were observed between these groups in the success rate of progenitor cell mobilization, in the number of CD34-positive cells collected or in the number of aphereses needed. HDT appeared to be somewhat more toxic in the elderly patients: a higher peak CRP value (P = 0.08) and longer in-hospital stay (P = 0. 05) were observed. No differences were found in transplant-related mortality or severe organ toxicity between these age groups except for oral mucositis grade >2, which tended to be more common in the elderly patients (P = 0.07). We conclude that progenitor cell mobilization and HDT supported by PBSCT is also feasible in selected elderly patients with NHL. Bone Marrow Transplantation (2000) 26, 737-741.     

Serum-soluble c-kit levels during mobilization of peripheral blood stem cells correlate with stem cell yield

c-Kit is expressed in hematopoietic stem cells and plays an important role in hematopoiesis. In 16 patients with malignancies, serum-soluble c-Kit levels and the expressions of c-KIT messenger RNA (mRNA) and protein in peripheral blood mononuclear cells were analyzed serially during 26 courses of peripheral blood stem cell (PBSC) mobilization after granulocyte colony-stimulating factor administration following chemotherapy for PBSC harvest. Serum-soluble c-Kit levels were significantly lower in patients than in controls (179.7+/-17.7 arbitrary units [AU]/mL versus 274.5+/-18.9 AU/mL; P < .001), decreasing after chemotherapy (167.7+/-18.2 AU/mL), increasing from day 14, and peaking at day 19 (193.3+/-16.4 AU/mL). The numbers of both c-Kit+ cells and CD34+ cells and granulocyte-macrophage colony-forming units in peripheral blood peaked at day 17, following the peak of the expression of c-KIT mRNA. Serum-soluble c-Kit levels showed a significant positive correlation with the numbers of CD34+ cells in both peripheral blood and leukapheresis products (r = 0.553, P < .01, and r = 0.640, P < .001, respectively) and changed at higher levels in patients with large numbers of PBSCs versus patients with small numbers of PBSCs (P < .05). Serum-soluble c-Kit may reflect the capacity for hematopoiesis after chemotherapy and may be useful in predicting the number of PBSCs that can be mobilized and harvested after mobilization, as well as for monitoring the timing for PBSC harvest.     

Identification of prognostic factors for plerixafor-based hematopoietic stem cell mobilization

The introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte-colony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ≥2.0 × 10(6) CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib, melphalan, radiotherapy, or autologous stem cell transplantation and regimen of plerixafor use in combination with chemotherapy had no significant effect on the efficiency of collection. In contrast, an age ≥65 years (odds ratio 0.331, 95% CI: 0.112-0.977, P < 0.05), a diagnosis of non-Hodgkin's lymphoma (odds ratio 0.277, 95% CI: 0.124-0.622, P < 0.01), and treatment with ≥ four chemotherapy regimens (odds ratio 0.366, 95% CI: 0.167-0.799, P < 0.05) were associated significantly with failed mobilization. The rate of successful mobilizations was decreased in patients treated with purine analogues (odds ratio 0.323, 95% CI: 0.096-1.094, P = 0.07) but increased in female patients (odds ratio 1.961, CI: 0.943-4.080, P = 0.07). Patients who are characterized by the above negative features could benefit potentially from further improvement in the mobilization strategy.     

Correlations between hematopoietic progenitor cell counts as measured by Sysmex and CD34+ cell harvest yields following mobilization with different regimens

PURPOSE: The Sysmex SE-9000 cell counter provides an estimate of immature cells referred to as hematopoietic progenitor cells (HPC). HPC counts should correlate with CD34+ counts in mobilized peripheral blood and apheresis to allow optimization of apheresis timing. METHODS: We correlated the HPC counts as measured in the immature information channel with CD34+ cell levels as determined by FACS (HPCA-2 antibody, Becton Dickinson) from mobilized peripheral blood in 40 samples (27 patients and three healthy donors) and in aphereses ( n=113, 41 patients and 20 healthy donors). RESULTS: In mobilized blood, HPC counts were correlated with CD34+ cells ( r=0.78, P<0.0001, n=40). The HPC counts were about 1.5-fold higher than CD34+ cell counts with a median (range) of 84 (1-747)/microl and 57 (1-370)/microl, respectively. In CD34+ selected cell preparations ( n=8), HPC counts were about fourfold lower than CD34+ cell counts with a median (range) of 179 (67-693)/microl and 760 (191-4309)/microl, respectively. In apheresis preparations, linear regression analyses were performed for the group of stem cell donors ( n=44), the group of lymphoma patients ( n=23), the multiple myeloma group ( n=21), and the group of solid tumors ( n=25). Interestingly, no correlation between HPC counts and CD34+ cell counts was found in the G-CSF-mobilized healthy donor group ( r=0.23, P=0.13). Pairing of HPC counts and CD34+ counts was effective in the group of patients receiving chemotherapy + G-CSF for stem cell mobilization: lymphoma group ( r=0.67, P=0.0005), multiple myeloma group ( r=0.56, P=0.008), and the group of solid tumors ( r=0.52, P=0.007). CONCLUSIONS: Lymphoma and multiple myeloma patients who were moderately pretreated and mobilized with chemotherapy and G-CSF showed the best results in correlation analyses even at low HPC counts. Therefore, HPC measurement can be used for timing of apheresis in these patients.     

Autologous stem cell transplantation in follicular non-Hodgkin's lymphoma

The failure of conventional chemotherapy to improve overall survival rates in follicular non-Hodgkin's lymphoma (NHL) has led to the development of alternative treatment regimens. One such regimen is high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT). In ASCT stem cells, harvested predominantly from peripheral blood, are used to repopulate the haemopoietic system after high-dose chemotherapy. Comparison of failure-free survival rates following ASCT, with those previously obtained with conventional chemotherapy, suggests a benefit for ASCT in patients who have previously responded to chemotherapy. Other factors that adversely influence the outcome of ASCT include large tumour burden and bcl-2 overexpression. Although ASCT in follicular NHL can prolong the period of remission, relapse is still common and can be caused either by contamination of the stem cell harvest with tumour cells, or regrowth of residual malignant cells not eradicated by the high-dose chemotherapy. Several strategies have been developed to reduce the rate of relapse, including in vitro purging of the stem cell product to remove tumour cells and using allogenic stem cells from HLA-matched donors with no history of malignant disease. While both these methods may have some benefit, they also have limitations. In vitro purging is labour intensive, costly and, as yet, the effect on relapse is unclear. Allogenic stem cell transplants have been associated with a reduced risk of relapse, but this is offset by increased transplant-related mortality. The most promising strategy to reduce the rate of relapse following ASCT is in vivo purging using rituximab, a monoclonal antibody to CD20. Rituximab mobilises mechanisms to kill lymphoma cells, and causes a rapid depletion of B cells from peripheral blood. Rituximab has demonstrated good efficacy as monotherapy in patients with both aggressive and indolent lymphoma and has shown very high response rates (>95%) when used in combination with HDT.     

Autologous hematopoietic stem cell transplantation for the treatment of aggressive non-Hodgkin's lymphoma. The experience of Polish lymphoma research group

We analysed the outcome of 200 patients, aged 38 (13-72) years, with aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (autoHSCT) in ten oncohaematological centres belonging to Polish Lymphoma Research Group (PLRG). The source of stem cells for transplantation was peripheral blood (autoPBSCT, n = 153), bone marrow (autoBMT, n = 40) or both blood and bone marrow (n = 7). The probability of overall survival (OS) and progression-free survival at 10 years was 51% (+/- 7%). The transplant-related mortality rate equalled 7%. In multivariate analysis, the only factor influencing independently the probability of OS was disease status at transplantation (p < 0.00001). The outcome of patients transplanted in first or subsequent complete remission or first partial remission (PR) was significantly better compared with subjects given autoHSCT in PR 2 or those with primary or secondary refractoriness. Regarding histological subtypes, the highest OS rate (87%) was observed for anaplastic large T cell lymphoma. The outcome after autoBMT was better compared with autoPBSCT (OS probability: 67% vs. 43%), although the difference did not reach statistical significance. We conclude that high-dose therapy followed by autoHSCT is an effective option for high-risk aggressive NHL. Remission status is a major factor determining long-term outcome. This should be taken into account when referring patients for autoHSCT.     

ESHAP plus G-CSF as an effective peripheral blood progenitor cell mobilization regimen in pretreated non-Hodgkin's lymphoma: comparison with high-dose cyclophosphamide plus G-CSF

The ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) regimen has been shown to be effective as an active salvage therapy for lymphoma. Mobilizing stem cells following ESHAP should decrease time to transplantation by making separate mobilizing chemotherapy (MC) unnecessary, while controlling a patient's lymphoma. We therefore assessed the mobilization potential of ESHAP plus G-CSF in 26 patients (ESHAP group) with non-Hodgkin's lymphoma (NHL) and compared these results with those of 24 patients with NHL who received high-dose (4 g/m2l) cyclophosphamide (HDCY) as MC (HDCY group). The age, sex, and radiotherapy to the axial skeleton were well matched between groups, but the number of patients with poor mobilization predictors was higher in the ESHAP group. Significantly higher numbers of CD34+ cells (x 10(6)/kg) (17.1+/-18.8 vs 5.8+/-5.0, P=0.03) and apheresis day 1 CD34+ cells (x 10(6)/kg) (5.5+/-6.6 vs 1.7+/-2.0, P=0.014) were collected from the ESHAP group than from the HDCY group, and the number of patients who achieved an optimal CD34+ cell target of 5 x 10(6)/kg was higher in the ESHAP group (81 vs 50%, P=0.022). Log-rank test revealed that time to target peripheral blood progenitor cell collection (> or =5 x 10(6)/kg) was shorter in the ESHAP group (P=0.007). These results indicate that ESHAP plus G-CSF is an excellent mobilization regimen in patients with relapsed and poor-risk aggressive NHL.     

Differential mobilization of myeloma cells and normal hematopoietic stem cells in multiple myeloma after treatment with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests.     

Hypercholesterolemia and its association with enhanced stem cell mobilization and harvest after high-dose cyclophosphamide+G-CSF

High-dose chemotherapy with autologous peripheral blood SCT is a common treatment option in several hematological and non-hematological malignancies. So far, prediction of successful stem cell mobilization and harvest is limited. Just recently, hypercholesterolemia was shown to increase mobilization of hematopoietic progenitor cells into the peripheral circulation in mice. On the basis of these results, we performed a retrospective multivariate analysis incorporating a variety of clinical parameters in 83 patients following high-dose cyclophosphamide+G-CSF treatment. Interestingly, we found a significant positive correlation between stem cell mobilization and harvest for plasma cholesterol and lactate dehydrogenase (LDH) only. Patients with hypercholesterolemia showed a substantially higher median peripheral blood CD34(+)-peak (126 vs 47/μL, P=0.003), higher median number of harvested CD34(+)-cells/kg (9.6 vs 7.4 × 10(6)/kg, P<0.001) and a sufficient number for at least one SCT in a remarkably higher proportion (84.9 vs 52.9%, P=0.003) compared with patients with normal cholesterol levels.     

In vivo purging and relapse prevention following ASCT

The combination of high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL) and is increasingly being considered as a first-line treatment for NHL patients with poor prognosis or poor outcomes from chemotherapy. However, there is a degree of relapse following the latter which is associated with high levels of tumour cell contamination of the stem cells and/or the presence of residual malignant cells in the host following chemotherapy. Reducing the rate of relapse can be achieved by pre-transplant purging of the stem cell graft followed by post-transplant maintenance to minimise residual disease. Various methods of in vitro purging have been shown to reduce, but not eliminate, the level of stem cell contamination and invariably result in a reduced harvest. To date, this has been reflected in disappointing outcomes for the patient. In contrast, in vivo purging with rituximab during the process of stem cell mobilisation and collection does not adversely affect the yield or function of stem cells and shows a significant improvement in the level of tumour cell contamination as measured by bcl-2 clearance. The relapse potential from residual malignant cells in the host can be addressed by a programme of post-transplant rituximab maintenance therapy. In one study 17 patients with follicular lymphoma who underwent ASCT with in vivo rituximab-purged stem cells, followed by rituximab maintenance, have all remained in complete response at a median follow-up of 12.4 months. The optimum in vivo rituximab purging protocol and the precise effect in terms of overall and disease-free survival are currently being evaluated but appear to present an attractive first-line alternative for NHL patients with poor prognosis or poor outcomes following chemotherapy.     

Poor hematopoietic stem cell mobilizers: A single institution study of incidence and risk factors in patients with recurrent or relapsed lymphoma

The purpose of this retrospective study was to determine the incidence and predictive factors if any, of mobilization failure in lymphoma patients referred for autologous stem cell transplantation. A total of 588 lymphoma patients were referred for transplant consultation from January 2003 to December 2004. Predictors of mobilization failure were evaluated using logistic regression analysis including diagnosis, mobilization regimen, age, sex, type and number of prior chemotherapies, bone marrow cellularity, platelet count, white count, prior bone marrow involvement with malignancy, and prior radiation therapy. Two hundred and six patients were eligible for transplantation and underwent stem cell mobilization. Twenty‐nine (14%) patients failed to mobilize adequate stem cells after the first attempt. For the entire group age (≥60 versus <60 years), diagnosis (Hodgkin's versus non‐Hodgkin's lymphoma), use of cytokines alone, platelet count <150 × 10⁹/L, and bone marrow cellularity <30% were significant predictors for mobilization failure on univariate analysis. In view of small number of patients multivariate analysis was not possible. However, a low platelet count (150 × 10⁹/L) was the only significant predictor when the analysis was restricted to non‐Hodgkin's lymphoma patients who were mobilized with chemotherapy. Mobilization failure rates are higher in patients with non‐Hodgkin's lymphoma compared with those with Hodgkin's lymphoma. In the subset of patients who undergo chemomobilization for non‐Hodgkin's lymphoma platelet count at the time of mobilization is a predictor of mobilization failure. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation

Haemopoietic stem cell therapy is an increasingly adopted procedure in the treatment of patients with malignant lymphoma. In this retrospective analysis, we evaluated 262 patients, 57 (22%) with Hodgkin's and 205 (78%) with non-Hodgkin's lymphomas (NHL), and 665 harvesting procedures in order to assess the impact of poor mobilization on survival and to determine the factors that may be predictive of CD34(+) poor mobilization. The mobilization chemotherapy regimens consisted of high-dose cyclophosphamide in 92 patients (35.1%) and a high-dose cytarabine-containing regimen (DHAP in 87 patients -(33.2%), MAD in 83 (31.7%)). The incidence of poor mobilizers (<2 x 10(6) CD34(+) cells/kg) was 17.9% overall, with a 10% of very poor mobilizers (< or = 1 x 10(6)/kg). Refractory disease status and chemotherapeutic load (>3 regimens) before mobilization played a negative role and were associated with poor mobilization. Survival analysis of all harvested patients showed an overall survival at 3 years of 71% in good mobilizers vs 33% in poor mobilizers (P=0.002). The event-free survival at 3 years was 23% in poor mobilizers and 58% in good mobilizers (P=0.04). We conclude that in NHL patients, poor mobilization status is predictive of survival.     

粒细胞集落刺激因子动员自体外周血干细胞移植治疗急性心肌梗死的临床研究

目的观察经皮经腔冠状动脉内移植自体外周血干细胞(PBSC)治疗急性心肌梗死(AMI)的疗效。方法自2003年11月至2005年1月共入选AMI患者70例,随机分为干细胞移植组和对照组,两组均为35例。干细胞治疗组在常规AMI治疗(药物与介入治疗)基础上应用粒细胞集落刺激因子(GCSF)皮下注射动员自体骨髄干细胞,连用5天,第6天分离外周血干细胞悬液,将采集后的干细胞悬液经OVERTHEWIRE球囊导管中心腔注入梗死相关动脉(IRA),进行外周血干细胞移植;对照组经AMI常规方法(药物与介入)治疗。在外周血干细胞动员、采集及经冠状动脉回输过程中观察其不良反应。两组患者在移植前及移植后6个月应用超声心动图评价左室形态及心功能变化,室壁节段性运动积分;比较两组患者生存率及心脏事件发生率。结果6个月时干细胞移植组心脏收缩末容积(ESV)明显减小[(63.8±23.9)ML比(52.6±20.3)ML,P=0.01],舒张末容积(EDV)无显著性变化[(134.2±36.7)ML比(119.2±30.3)ML,P=0.07];左室射血分数(LVEF)显著增高[(50.0±8.2)%比(57.1±7.8)%,P<0.001];左室壁节段性运动积分指数(WMSI)明显减低[(1.219±0.190)比(1.101±0.118),P<0.001]。对照组介入术前及术后6个月随访ESV、EDV、LVEF及WMSI均无统计学差异(P=0.490、0.259、0.117、0.395)。两组术后6个月生存率及心脏事件发生率无统计学差异。不良反应:在PBSC动员、分离、采集及回输中总的不良反应共25例次,其中动员时不良反应占37.1%(13/35),分离和采集中的不良反应占14.3%(5/35),经冠状动脉回输过程中出现的不良反应占20.0%(7/35)。结论经皮经腔冠状动脉内移植自体PBSC治疗AMI可以在近期有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能。