Just‐in‐time rescue plerixafor in combination with chemotherapy and granulocyte‐colony stimulating factor for peripheral blood progenitor cell mobilization

Plerixafor, a recently approved peripheral blood progenitor cell mobilizing agent, is often added to granulocyte‐colony stimulating factor (G‐CSF) to mobilize peripheral blood progenitor cells in patients with lymphoma or myeloma who cannot mobilize enough CD34+ cells with G‐CSF alone to undergo autologous stem cell transplantation. However, data are lacking regarding the feasibility and efficacy of just‐in‐time plerixafor in combination with chemotherapy and G‐CSF. We reviewed the peripheral blood stem cell collection data of 38 consecutive patients with lymphoma (Hodgkin's and non‐Hodgkin's) and multiple myeloma who underwent chemomobilization and high‐dose G‐CSF and just‐in‐time plerixafor to evaluate the efficacy of this treatment combination. All patients with multiple myeloma and all but one patient with lymphoma collected the minimum required number of CD34+ cells to proceed with autologous stem cell transplantation (>2 × 10⁶/kg of body weight). The median CD34+ cell dose collected in patients with non‐Hodgkin lymphoma was 4.93 × 10⁶/kg of body weight. The median CD34+ cell dose collected for patients with multiple myeloma was 8.81 × 10⁶/kg of body weight. Plerixafor was well tolerated; no grade 2 or higher non‐hematologic toxic effects were observed. Am. J. Hematol. 88:754–757, 2013. © 2013 Wiley Periodicals, Inc.     

Efficacy of pre-emptively used plerixafor in patients mobilizing poorly after chemomobilization: a single centre experience

A significant proportion of patients with lymphoid malignancies are hard‐to‐mobilize with a combination of chemotherapy plus granulocyte colony‐stimulating factor (G‐CSF) (chemomobilization). Plerixafor is a novel drug used to improve mobilization of blood stem cells. However, it has been studied mainly in association with G‐CSF mobilization. We evaluated the efficacy of ‘pre‐emptive’ use of plerixafor after chemomobilization in patients who seem to mobilize poorly. During a 15 month period, altogether 63 patients with lymphoid malignancies were admitted to our department for blood stem cell collection. Sixteen patients (25%) received plerixafor after the first mobilization due to the low blood (B) CD34⁺ cell counts (n = 12) or poor yield of the first collection (n = 4). The median number of plerixafor injections was 1 (1–3). The median B‐CD34⁺ count after the first plerixafor dose was 39 × 10⁶/L (<1–81) with the median increase of fivefold. Stem cell aphaereses were performed in 14/16 patients (88%) receiving plerixafor and a median of 2.9 × 10⁶/kg (1.6–6.1) CD34⁺ cells were collected with a median of one aphaeresis (1–3). Altogether 13/16 patients mobilized with a combination of chemomobilization and plerixafor received high‐dose therapy with stem cell support and all engrafted. Pre‐emptive use of plerixafor after chemomobilization is efficient and safe and should be considered in poor mobilizers to avoid collection failure. In patients with low but rising B‐CD34⁺ counts, the use of plerixafor might be delayed as late mobilization may occur. Further studies are needed to optimize patient selection and timing of plerixafor.     

Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma

The combination of cyclophosphamide and granulocyte‐colony stimulating factor (G‐CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G‐CSF alone or etoposide followed by G‐CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G‐CSF, etoposide and G‐CSF, and G‐CSF alone (including nonmyelosuppressive chemotherapy followed by G‐CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 × 10⁶/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 × 10⁶ CD34‐positive cells/kg or PFS after ASCT. G‐CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.     

Chemomobilization with high‐dose etoposide and G‐CSF results in effective and safe stem cell collection in heavily pretreated lymphoma patients: report from a single institution study and review

The optimal mobilization strategy prior to autologous stem cell transplantation (auto‐SCT) for patients with lymphoma is yet to be determined. We reviewed our institutional experience using chemomobilization with high‐dose (HD) etoposide (1.6 g/m²) and G‐CSF (300 μg/day) in 79 patients with lymphoma. The majority (76%) had received at least two prior regimens of chemotherapy, and 12 (15.2%) patients had previously failed to mobilize following HD cyclophosphamide or DHAP or ICE with G‐CSF. HD etoposide and G‐CSF chemomobilization resulted in successful collection (>2 × 10⁶ CD34+ cells/kg) in 82.3% of patients within a median 2 (1–6) apheresis days. Patients had stem cells collected between days +8 and +15, with a median +12 day. Median total CD34+ cells/kg collected was 5.95 × 10⁶ (0.1–36.8). Seventy‐one percent of patients yielded >2 × 10⁶ CD34+ cells/kg in ≤2 d of apheresis and were defined as good mobilizers. While median CD34+ cells/kg collected for good mobilizers was 7.6 × 10⁶, it was 2.6 × 10⁶ for poor mobilizers (P < 0.001). This regimen was safe with a low rate of febrile neutropenia (7.6%) and acceptable rates of RBC (40.5%) and platelet transfusions (22.8%). Hematopoietic recovery after auto‐SCT was achieved on expected time. Therapy‐related myelodysplastic syndrome/acute myeloid leukemia occurred in only one patient (1.3%) with in a median follow‐up of 16 months after chemomobilization. We conclude that HD etoposide and G‐CSF chemomobilization appear to result in effective, tolerable, and safe stem cell collection in the majority of heavily pretreated lymphoma patients.     

European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization

The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 × 10(6) CD34+ cells/kg: 81.6%; >5.0 × 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 × 10(6) CD34+ cells/kg: 64.8%; >5.0 × 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 × 10(6) CD34+ cells/kg: 81.5%; >5.0 × 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required.     

Retrospective comparison of filgrastim plus plerixafor to other regimens for remobilization after primary mobilization failure: clinical and economic outcomes

We performed a retrospective analysis to evaluate clinical and economic outcomes in patients receiving remobilization therapy after primary mobilization failure. Our primary endpoint was to compare filgrastim plus plerixafor to other regimens in their ability to collect a target cell dose of at least 2 million CD34+ cells/kg (cumulative). Of 96 consecutive patients who failed their primary mobilization therapy and in whom a second mobilization was attempted, remobilization consisted of filgrastim plus plerixafor (n = 38), filgrastim with or without sargramostim (n = 43), or chemotherapy plus filgrastim (n = 15), 84% of filgrastim/plerixafor patients were able to collect at least 2 million CD34+ cells/kg from both mobilizations, compared to 60% of patients mobilized with chemotherapy/filgrastim and 79% of the filgrastim ± sargramostim patients (P = 0.17). However, when combined with cells collected from the first mobilization, 53% of filgrastim/plerixafor patients reached the target of 2 million CD34+ cells in one apheresis, compared to 20% of those receiving chemotherapy/filgrastim and 28% of those receiving filgrastim ± sargramostim (P = 0.02). Resource utilization, mobilization drug costs, clinical care costs, and total costs were significantly different. We conclude that while filgrastim/plerixafor is the most efficient remobilization strategy, those clinical benefits may not translate into lower cost, especially when multiple days of plerixafor administration are required.     

Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G-CSF administration

Plerixafor, given on day 4 of G-CSF treatment is more effective than G-CSF alone in mobilizing hematopoietic progenitor cells. We tested a strategy of preemptive plerixafor use following assessment of the peak mobilization response to 5 days of G-CSF. Patients were eligible for plerixafor if, on day 5 of G-CSF, there were <7 circulating CD34+ cells/μL or if <1.3 × 10(6) CD34+ cells/kg were collected on the first day of apheresis. Plerixafor (0.24?mg/kg s.c.) was given on day 5 of G-CSF followed by apheresis on day 6. This was repeated for up to two additional doses of plerixafor. The primary end point of the study was the percentage of patients who collected at least 2 × 10(6) CD34+ cells/kg. Twenty candidates for auto-SCT enrolled on the trial. The circulating CD34+ cell level increased a median of 3.1 fold (range 1-8 fold) after the first dose of plerixafor and a median of 1.2 fold (range 0.3-6.5 fold) after the second dose of plerixafor. In all, 15 out of 20 (75%) patients achieved the primary end point. In conclusion, the decision to administer plerixafor can be delayed until after the peak mobilization response to G-CSF has been fully assessed.     

Plerixafor on‐demand combined with chemotherapy and granulocyte colony‐stimulating factor: significant improvement in peripheral blood stem cells mobilization and harvest with no increase in costs

To date, no prospective study on Plerixafor ‘on‐demand’ in combination with chemotherapy and granulocyte colony‐stimulating factor (G‐CSF) has been reported. We present an interim analysis of the first prospective study in which Plerixafor was administered on‐demand in patients affected by multiple myeloma and lymphoma who received high dose cyclophosphamide or DHAP (dexamethasone, cytarabine, cisplatin) plus G‐CSF to mobilize peripheral blood stem cells (PBSC). One hundred and two patients were evaluable for response. A cohort of 240 patients receiving the same mobilizing chemotherapy was retrospectively studied. Failure to mobilize CD34⁺ cells in peripheral blood was reduced by ‘on‐demand’ strategy compared to conventional mobilization; from 13·0 to 3·0% (P = 0·004). Failure to harvest CD34⁺ cells 2 × 10⁶/kg decreased from 20·9 to 4·0% (P = 0·0001). The on‐demand Plerixafor strategy also resulted in a lower rate of mobilization failure (P = 0·03) and harvest failure (P = 0·0008) when compared to a ‘bias‐adjusted set of controls’. Evaluation of economic costs of the two strategies showed that the overall cost of the two treatments were comparable when salvage mobilizations were taken into account. When in combination with cyclophosphamide or DHAP plus G‐CSF, the ‘on‐demand’ use of Plerixafor showed, in comparison to conventionally treated patients, a significant improvement in mobilization of PBSC with no increase in overall cost.     

Haematopoietic stem cell mobilization with plerixafor and G-CSF in patients with multiple myeloma transplanted with autologous stem cells

A proportion of patients with multiple myeloma (MM) who have already undergone autologous stem cell transplantation (autoSCT) might benefit from a further transplantation. For this, they might need to undergo another round of stem cell mobilization. We analyzed retrospectively the outcomes of stem cell mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) in a group of 30 patients who had undergone autoSCT previously, and in 46 other patients. The previously transplanted patients were significantly different from the remaining patients with respect to the intensity and number of previous therapies. We observed that the median peripheral blood concentration of CD34+ cells after the first administration of plerixafor was lower in previously transplanted (19 cells/μL) than in other patients (30 cells/μL, P < 0.05). Despite a comparable number of apheresis sessions being performed, the median total yield of CD34+ cells was significantly lower in the previously transplanted than in the remaining patients (2.8 × 10(6) cells/kg vs. 4.2 × 10(6) cells/kg, P < 0.05). However, successful collection of at least 2.0 × 10(6) CD34+ cells/kg was achieved finally in a similar proportion of previously transplanted and other patients (70% vs. 82.6%). Our data suggest that stem cell mobilization with plerixafor and G-CSF might overcome the negative effect of prognostic factors for poor stem cell mobilization in patients with MM who have undergone autoSCT previously.     

Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program

The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 μg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/μL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 10(6) CD34+ cells/kg (1.6-5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 10(6) CD34+ cells/kg (0-24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.     

Hematopoietic recovery kinetics predicts for poor CD34+ cell mobilization after cyclophosphamide chemotherapy in multiple myeloma

Autologous stem cell transplantation is an important part of therapy in patients with multiple myeloma. Some patients fail to collect the desired number of stem cells while others require multiple apheresis to reach the desired apheresis target. The aim of this study was to determine the predictive factors and if the hematopoietic kinetics of recovery were predictive for outcome of stem cell mobilization in cyclophosphamide + growth factor (CY-GF) mobilized patients. Three hundred and ninety six consecutive CY-GF mobilization attempts between January 2000 and December 2009 at Mayo Clinic, Rochester, MN were analyzed. Patients were divided into three groups: optimal (>5 × 10(6) CD34/kg), suboptimal (2-5 × 10(6) CD34/kg) and poor (<2 × 10(6) /kg CD34+ cells) mobilization groups. About 86% of patients had optimal stem cell collection, whereas 8% had suboptimal collection and 6% had poor (or failed) collections. Age, Hb, WBC, and platelet levels had an impact on mobilization results. Time to peripheral blood (PB) CD34+cells >10/μL predicted for efficiency of collection and the interval between recovery of WBC>1 post-CY to PB CD34+ cells>10 was shorter in the optimal collection groups. These findings suggest that for patients with a PB CD34+ cell count below 10/μL on Day 13 following CY or 1 day after the WBC>1 × 10(9) /L, addition of plerixafor may be helpful to salvage the mobilization attempt.     

Peripheral blood progenitor cell (PBPC) transplantation with a single apheresis in patients with lymphoma,myeloma and solid tumors

Abstract: The aim of this study was to investigate if a single apheresis after peripheral blood progenitor cell (PBPC) mobilization can be used to rescue patients receiving high dose chemotherapy (HD.CHE) as treatment for an underlying malignancy. Eighteen consecutive patients who were admitted to the transplant unit for treatment were leukapheresed following mobilization with one of the following protocols: group I: rHuG–CSF alone, group II: conventional chemotherapy (C.CHE)+rHuG–CSF or rHuGM–CSF and group III: high dose Cytoxan (HD.CTX)+rHuG–CSF. The optimal day for leukapheresis was determined by following white blood cell counts (WBC), mononuclear cell counts (MNC) and CD34⁺ cell counts daily. Granulocyte – macrophage colony-forming cells (GM–CFC) assay was performed at the leukapheresis product and prior to reinfusion. All patients proceeded directly to ablative therapy according to their underlying malignancy. PBPC from single apheresis were reinfused to all patients and cytokines started 24 h after infusion. Hematologic recovery after HD.CHE was the parameter used to ensure successful engraftment. We have been able to recover adequate number of PBPC for transplantation with a single apheresis in all patients. The number of infused cells were for groups I, II and III: (1) median number of MNC 4.7, 3.58 and 2.79 × 10⁸/kg, respectively (2); median number of CD34⁺ cells 4.4, 2.8, 2.7 × 10⁶/kg, respectively. The median apheresis day was 6, 16 and 16, respectively. Recovery times to granulocyte count >0.5 × 10⁹/L was 9 d (range 9–12) and to platelets >20 × 10⁹/L was 12 d (range 1–135); 17/18 patients have engrafted successfully independent of the mobilization method used.These data suggest that sufficient PBPC can be harvested at a single leukapheresis for hemopoietic rescue after myeloablative therapy. Rapid hematologic recovery occurs when cytokines alone after conventional or HD.CHE are used for mobilization. Results of collection products and hematopoietic recovery are independent of the mobilization technique used.     

A risk-based approach to optimize autologous hematopoietic stem cell (HSC) collection with the use of plerixafor

Autologous hematopoietic stem cell (HSC) transplant is an effective treatment for patients with hematological malignancies. Unfortunately, 15-30% of patients fail to mobilize a sufficient number of HSCs for the transplant. Plerixafor is now used as a salvage mobilization regimen, with good success. We describe here a risk-based approach for the use of plerixafor, based on the circulating CD34(+) cell count and the CD34(+) cell dose collected after 4 days of G-CSF, that identifies potential poor HSC mobilizers upfront. A total of 159 patients underwent HSC collections using this approach. Of these, 55 (35%) were identified as high risk owing to low CD34(+) cell number or low yield on day 1 of collection, and received plerixafor on the subsequent days of collection. Of the 159 patients, 151 (95%) were able to provide adequate collections with the first mobilization attempt in a median of 1.7 days using this approach. Of the eight who failed initial mobilization, 5 successfully underwent re-mobilization with plerixafor and G-CSF and 3 (1.9%) were mobilization failures. This approach helped to control the overall cost of HSC collections for our BMT program by decreasing the need for remobilization, reducing the number of collection days and avoiding the use of plerixafor in all patients.     

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16?mg/kg/day, with a subsequent dose increase in one case to 0.24?mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24?mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24?mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.     

Safety and efficacy of healthy volunteer stem cell mobilization with filgrastim G‐CSF and mobilized stem cell apheresis: results of a prospective longitudinal 5‐year follow‐up study

Background and Objectives G‐CSF‐mobilized peripheral blood stem cells have long replaced marrow as the major source for allogeneic transplants. Conclusive evidence questioning the long‐term safety of G‐CSF for donors has not been provided, but the cumulative number of followed donors remains insufficient to rule out rare adverse events. A long‐term active follow‐up study of G‐CSF‐mobilized healthy volunteer donors was therefore performed. Patients and Methods Two hundred and three successive donors were evaluated pre‐apheresis, subjected to G‐CSF‐mobilization/apheresis, and actively followed for 5 years by the same physicians and laboratories. Follow‐up laboratory work included standard biochemical/haematological tests and T‐cell phenotyping. Results Donor epidemiology was typical for reported stem cell donor cohorts. Acute adverse effects of G‐CSF and apheresis were mild and transient, consistent with the previous reports. Mean circulating CD34⁺ cells after nine doses of G‐CSF were 124 per μl. Other biochemical/haematological parameters were also altered, consistent with G‐CSF treatment. Spleen enlargement was modest. At first follow‐up, all clinical and laboratory parameters had normalized. Leucocyte/lymphocyte counts and CD4/CD8 ratios were the same as during premobilization work‐up and remained unchanged throughout. A single severe but likely unrelated adverse event, a case of papillary thyroid carcinoma, was reported. Conclusion The studies add an observation time of almost 500 donor years to the growing body of evidence of the long‐term safety of G‐CSF for allogeneic donor stem cell mobilization.     

Plerixafor is effective and safe for stem cell mobilization in heavily pretreated germ cell tumor patients

Up to 10% of germ cell tumor patients require salvage high-dose chemotherapy with stem cell support, achieving cure rates in the range of 10-60%. Stem cell mobilization may be difficult in these patients because of multiple lines of treatment known to seriously hamper stem cell recovery. Plerixafor significantly enhances the success of the CD34+ cell harvest, even in cases where prior mobilization attempts have failed. Six germ cell tumor patients provided informed consent and were included in the compassionate use program. All patients were heavily pretreated, with a median of 3.5 prior lines of therapy. All failed prior mobilization with G-CSF in combination with chemotherapy. Five patients yielded a median of 2.6 × 10(6) CD34+ cells per kg body weight in a median of 4 apheresis days when plerixafor was used. Three patients underwent subsequent high-dose chemotherapy with autologous stem cell support. Median time to leukocyte engraftment was 11 days. Median time to platelet engraftment was 12.5 days, both of which are comparable to previous historical data. Accordingly, plerixafor seems to be safe and effective in germ cell tumor patients who have failed prior mobilization therapy. Larger prospective studies are warranted to further assess its use in germ cell cancer.     

How I treat patients who mobilize hematopoietic stem cells poorly

Transplantation with 2-5 × 10(6) mobilized CD34(+)cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established. To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify poor mobilizers, and what are the criteria for preemptive and immediate salvage use of plerixafor.     

Mobilization and harvesting of peripheral blood stem cells in pediatric patients with solid tumors

Survival of patients with high‐risk pediatric solid tumors has improved with the introduction of a high‐dose chemotherapy regimen and autologous stem cell rescue. Here, we present our data regarding the evaluation of the efficacy and safety of hematopoietic stem cell mobilization and harvesting in children with solid tumors. From November 2002 to March 2010, 85 children underwent autologous peripheral blood stem cell collection; 35 (41.1%) of them weighed less than 20 kg and were diagnosed with neuroblastoma, Wilms' tumor, medulloblastoma, yolk sac sarcoma, or non‐Hodgkin's lymphoma. The mobilization regimens included disease‐specific chemotherapy plus granulocyte colony‐stimulating factor in most of the patients. The median age and weight at the time of apheresis was 36 months and 13.5 kg, respectively. Large‐volume leukapheresis was performed with the aim of reducing the psychological and financial impact of leukapheresis by reducing the number of procedures while collecting a large number of cells. The median number of mobilization and leukapheresis procedures per case was one. The pre‐apheresis CD34+ cell count ranged from 2 to 845 µL, with a median of 24 µL. A median of four patient blood volumes was processed per procedure, lasting 279 min (range, 113–420 min). A radial catheter was used for harvesting in 35 procedures (71.4%). The median yield of CD34+ cells was 6.6 × 10⁶/kg per patient. The targeted dose of 5 × 10⁶/kg CD34+ cells was realized in 80% of patients. The tolerance of peripheral blood stem cell collection in our patients was good. In conclusion, the collection of peripheral blood stem cells is an effective and safe procedure, even when conducted on the youngest children.     

Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma

 We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5–50 μg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 μg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 μg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2–5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2×10⁶ CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 μg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2×10⁶ CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 μg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 μg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF. Received: December 15, 1998 / Accepted: April 28, 1999     

High CD8+ lymphocyte dose in the autograft predicts early absolute lymphocyte count recovery after peripheral hematopoietic stem cell transplantation

Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non‐hematological cancers. Sixty‐five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre‐collection absolute lymphocyte count (ALC). The CD8+ lymphocyte dose in the autograft and the pre‐mobilization ALC were independently associated with ELR (P < 0.001 and P = 0.008, respectively). CD8+ lymphocyte doses higher than 0.1 × 10⁹/kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98–127.69] and this cutoff may be used to predict ELR (P = 0.001, area under the curve 0.75, 95% CI 0.62–0.88). Mobilization with granulocyte colony‐stimulating factor (G‐CSF) alone, the pre‐collection ALC and the number of apheresis sessions were independently associated with the CD8+ lymphocyte dose (P = 0.04, P = 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD8+ lymphocyte dose (r_s = 0.68, P < 0.001). Median pre‐mobilization ALC was higher than pre‐collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G‐CSF (1090 vs. 758 lymphocytes/μL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G‐CSF (1920 vs. 1539/μL, respectively; P = 0.23). These results suggest that the CD8+ lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G‐CSF significantly decreases the pre‐collection ALC, especially in patients with low pre‐mobilization ALC. Am. J. Hematol, 2009. © 2008 Wiley‐Liss, Inc.