Previous Mobilization Attempt Research Articles

Impact of plerixafor use in the mobilization of blood grafts for autologous hematopoietic cell transplantation.

Plerixafor (PLER), a reversible antagonist of the CXC chemokine receptor type 4, has been in clinical use for mobilization of blood grafts for autologous hematopoietic cell transplantation (AHCT) for about 15 years. Initially PLER was investigated in placebo-controlled trials with the granulocyte colony-stimulating factor (G-CSF) filgrastim. It has also been used in combination with chemotherapy plus G-CSF in patients who had failed a previous mobilization attempt or appeared to mobilize poorly with current mobilization (preemptive use). This review summarizes what is known regarding addition of PLER to standard mobilization regimens. PLER increases mobilization of CD34+ cells, decreases the number of apheresis sessions needed to achieve collection targets and increases the proportion of patients who can proceed to AHCT. It appears also to increase the amount of various lymphocyte subsets in the grafts collected. In general, hematologic recovery after AHCT has been comparable to patients mobilized without PLER, although slower platelet recovery has been observed in some studies of patients who mobilize poorly. In phase III studies, long-term outcome has been comparable to patients mobilized without PLER. This also appears to be the case in patients receiving plerixafor for poor or suboptimal mobilization of CD34+ cells. In practice, PLER is safe and has not been shown to increase tumor cell mobilization.

Comparison of different plerixafor-based strategies for adequate hematopoietic stem cell collection in poor mobilizers

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p < 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

EVALUATION OF BLOOD CELL COUNT USING THE SYSMEX XN-1000 AUTOMATIC HEMATOLOGY ANALYZER TO OPTIMIZE COLLECTION OF PERIPHERAL BLOOD PROGENITOR CELLS BY LEUKAPHERESIS

Autologous stem cell transplantation (ASCT) is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell (HSC) collection. The objective was to identify characteristics that can influence the effectiveness of mobilization and create a model to predict the success of mobilization in candidates for ASCT. This was a retrospective study, and data from patient candidates for ASCT between 09/2015 and 12/2021 were analyzed. Participants were assisted in five hospitals and laboratory procedures were performed at the Cell Processing Center (CPC) of Cetebio/Fundação Hemominas, Brazil. The medical records of the participants were reviewed to obtain the following information: gender, age, weight, diagnosis, mobilization, mobilization cycle, number of previous chemotherapy regimens and previous radiotherapy. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood (PB) blood count. Enumeration of CD34+ cell was performed using the ISHAGE protocol. The blood count was performed using an automated counter (SYSMEX XN-1000 AS-01). The studied outcome, good mobilization, was defined as a viable CD34+ cell count ≥ 20/uL in the PB. Model derivation was performed using logistic regression. The level of classification accuracy of model was tested in a subset of participants. The study population included 807 patients, 413 (51%) of whom were male. The median age was 54 (1-74) years. Multiple myeloma was the most common diagnosis (58,2%), followed by lymphoma. Of the 807 participants, 74 failed in previous mobilization attempts, totaling 881 cycles of mobilizations and collection attempts. Of the 623 participants, 353 were good mobilizers. Increasing patient weight, lower mean corpuscular volume (MCV), higher nucleated red blood cells (nRBC), peripheral blood mononuclear cells (PBMC), and immature granulocyte count were significantly associated with good mobilization. In addition, participants diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma (OR=1.92; 95%CI: 1.21 – 3.05; P=0.006). The model was applied to the validation set to identify patients who underwent apheresis (CD34+ cells count ≥ 10 μL), resulting in a sensibility of 69%, a specificity of 95%, positive predictive value of 98%, a negative predictive value of 50%. The results of our study are extremely relevant to institutions that do not have a flow cytometer and rely on other institutions to define HSC collection by apheresis. Cetebio serves nine transplant centers. The centers that perform the collection of HSC are located between 40 to 568 km away from Cetebio (place of quantification of CD34+ cells). Predicting the outcome of mobilization may allow the adoption of complementary measures, such as the use of plerixafor. Furthermore, it would better optimize the collection of CPH by apheresis. Thus, it would be possible to avoid additional collection days, reducing costs and risks related to administration of additional doses of G-CSF, catheter maintenance and prolonged hospital stay. Success in mobilization was greater in participants who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher weight and levels of nRBC, immature granulocytes, and PBMC, as well as lower levels of MCV, were associated with successful mobilization.

Vinorelbine-Based Hematopoietic Stem-Cell Mobilization: A More Effective, Low-Cost Alternative to Conventional Chemotherapy

INTRODUCTIONAutologous stem cell transplantation (ASCT) is the cornerstone of the treatment of several hematological malignancies, including multiple myeloma (MM) and aggressive and relapsed/refractory lymphomas. The mobilization of peripheral blood stem-cells (PBSC) for ASCT, however, is not always possible, with failure rates around 20%. Although the introduction of drugs such as plerixafor has greatly improved on this issue, they are still expensive and inaccessible in lower-income countries. The use of chemomobilization with drugs such as cyclophosphamide, etoposide, and others are a more affordable option, but they still lead to severe neutropenia, and in some settings to longer inpatient stays, with the associated costs.Vinorelbine is a vinca alkaloid which has already been reported to be effective in PBSC mobilization in combination with granulocyte growth-factor (G-CSF). We tested whether vinorelbine-based strategy for PBSC mobilization would be more effective and less resource-consuming than mobilization with conventional chemotherapy in combination with GCSF. METHODSThis is a retrospective, single-center analysis of the 74 patients with plasma cell disorders and lymphomas who underwent PBSC mobilization in our institution from January 2016 until May 2018.Until March 2017 PBSC mobilization at our institution was done with cyclophosphamide 2 gm/sqm plus G-CSF, for plasma-cell disorders, or with conventional chemotherapy regimens, such as ICE (ifosfamide, carboplatin and etoposide) and DHAP (dexamethasone, cytarabine and cisplatin) plus G-CSF for lymphomas. Peripheral CD34+ cells were counted daily after white blood cells reached > 1000 cells/μl, and leukapheresis was performed on the first day of peripheral CD34+ cell count > 10/μl, with a target of at least 2x106CD34+ cells/kg. Due to local limitations and the unpredictability of the day of PBSC harvesting, the whole procedure-from chemotherapy administration to apheresis-was done in the inpatient setting. From March 2017 onwards, in an effort to reduce costs and increase efficacy, a vinorelbine-based protocol for mobilization with a 35 gm/sqm dose on day one, GCSF 12-16 mcg/kg/day from day 4 onwards and PBSC harvesting on day 8, or latter, when peripheral CD34+ cell count was higher than 10/μl was implemented for all patients, irrespective of their diagnosis. RESULTSPatients' characteristics are summarized in Table 1. Seventy-four patients underwent mobilization, 38 (51.3%) with vinorelbine and 36 (47.3%) with conventional chemotherapy, with an 81.1% success rate. Patients had a median age of 54 years, with a median of one previous treatment line, which included radiotherapy in 22.4% of patients. Plasma-cell disorders were the most frequent diagnosis (59.5%). Due to a shortage of melphalan, only 52.7% of patients have proceeded to ASCT so far. Vinorelbine-based PBSC mobilization resulted in higher success rates (92.1% vs. 69.4%, p=0.017), lower length of hospital stay (median of 3 vs. 16 days, p<0.001), more predictable day of the first leukapheresis (median 7 days after chemotherapy, range 7-9 vs. 10 days, range 9-18) and a higher count of peripheral CD34+cells prior to leukapheresis (median 47.74 vs. 27.24 cells/μl, p=0.08) than mobilization with conventional chemotherapy-regimens (Figure 2). Patients in both groups were comparable regarding all variables depicted in Table 1, except for failure in a previous PBSC mobilization attempt (18.4% in the vinorelbine group vs. 2.8% in the conventional chemotherapy group, p=0.056). Two (5.3%) patients in the conventional chemotherapy group developed febrile neutropenia (FN), one of whom died. No episodes of FN or death were observed in the vinorelbine group. Progression-free survival and time for neutrophils engraftment after ASCT did not differ between groups (Figure 2). Direct costs of both strategies were roughly the same. CONCLUSIONSVinorelbine is a safe, effective and less costly strategy for PBSC mobilization in patients undergoing ASCT. It is associated with less toxicity and mobilization failures, shorter hospital length of stay and yields higher CD34+ blood cell counts, all of which decrease the indirect costs associated with PBSC, without loss of efficacy.Vinorelbine is a low-cost effective alternative to PBSC mobilization that can be useful in resource-constrained settings, where access to costly drugs, such as plerixafor, is limited. DisclosuresDe Paula:Hematology and Transfusion Medicine Center, University of Campinas: Employment. Ozelo:Pfizer: Honoraria, Research Funding, Speakers Bureau; Shire: Honoraria, Research Funding, Speakers Bureau; Grifols: Honoraria; Novo Nordisk: Honoraria, Research Funding, Speakers Bureau; Bioverativ: Honoraria, Research Funding; BioMarin: Honoraria, Speakers Bureau.

Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario.

High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10-18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization.■ It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.

The High Effect of Chemomobilization with High-Dose Etopside + Granulocyte-Colony Stimulating Factor in Autologous Hematopoietic Peripheral Blood Stem Cell Transplantation: A Single Center Experience.

Autologous hematopoietic stem cell transplantation (auto-HSCT) provides hematopoietic support after high-dose chemotherapy and is the standard of care for patients with multiple myeloma (MM), chemo sensitive relapsed high or intermediate grade non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). However, yields of hematopoietic stem cells vary greatly between patients, and the optimal strategy to mobilize hematopoietic stem cells into peripheral blood for collection has not been defined yet. We investigated the efficacy and safety of chemo mobilization with an intermediate dose etoposide (VP-16; 200 mg/m2 on days 1-3) and granulocyte-colony stimulating factor (G-CSF)(5 µg/kg twice daily from day 4 through the final day of collection). We reviewed our institutional experience with 91 patients (71 MM, 12 HL, 8 NHL) mobilized with this regimen. VP-16 + G-CSF resulted in successful mobilization in 95.55% of the patients (on one patient stem cell collection with plerixafor was applied), including 76 patients (83.52%) whose stem cells were collected successfully in a single day. Collection was managed between min. D8 and max. D17. Patient age, gender, exposure to previous irradiation and chemotherapy, previous mobilization attempts, and disease characteristics were not considered during selection. Adverse effects of the regimen included supportive transfusions and fevers requiring hospitalization or intravenous antibiotics. VP-16 and G-CSF appears to be a safe and effective mobilization regimen for patients with multiple myeloma, non-Hodgkin’s lymphoma and Hodgkin’s lymphoma undergoing autologous stem cell transplantation, producing excellent stem cell yield with the majority of patients requiring 1 day of apheresis.

Long-term follow up of patients proceeding to transplant using plerixafor mobilized stem cells and incidence of secondary myelodysplastic syndrome/AML

We report the long-term follow up of 49 patients (pts) enrolled on plerixafor compassionate use protocol. Thirty-seven pts (76%) had failed one previous mobilization attempt, while 12 (24%) had failed two or more previous attempts. Using the combination of plerixafor and granulocyte colony-stimulating factor, we collected2.5 × 10(6) CD34+cells/kg in 33 pts (67%). Forty-three of the 49 pts proceeded to an auto-SCT (ASCT). The median days to WBC and platelet engraftment were 11 (range, 9-13 days) and 16 (range, 11-77 days) days post ASCT, respectively. The median WBC count, Hb and platelet counts 1 year after ASCT were 4.7 × 10(9)/L, 12.2 g/dL and 109 × 10(9)/L, respectively. With median follow up of 42 months (range <1-54 months), 21 pts had evidence of disease progression. Five pts developed myelodysplastic syndrome (MDS)/AML at median of 29 months post ASCT. The cumulative incidence of MDS/AML at 42 months was 17% (95% confidence interval, 6 to 32%). Development of secondary MDS/AML in pts proceeding to ASCT after plerixafor mobilization needs to be studied further in a larger cohort.

Plerixafor use for peripheral blood stem cell mobilization in Korea

Peripheral blood stem cell (PBSC) mobilization is a prerequisite for the success of autologous stem cell transplantation (ASCT), and the infusion of adequate number of CD34+ hematopoietic progenitor cells is correlated with successful engraftment [1]. Traditionally, chemotherapeutic agents such as cyclophosphamide in combination with granulocyte-colony stimulating factor (G-CSF) have been used for mobilization of hematopoietic stem cells from bone marrow into peripheral blood. However, approximately 10-30% of patients who are at risk of mobilization failure are unable to mobilize minimum required number of PBSCs (≥2.0×106 CD34+ cells/kg) for the success of ASCT [2], and consequently fail to undergo ASCT. Plerixafor (AMD3100), a small molecule inhibitor of stromal cell-derived factor-1α binding to the CXCR4 receptor, was introduced as a solution for patients who show inadequate mobilization of CD34+ PBSCs. Results of Phase I/II trials demonstrated the efficacy of plerixafor, and a subsequent Phase III study showed that the use of plerixafor in combination with G-CSF significantly increased the number of CD34+ PBSCs, compared to G-CSF alone [3]. Plerixafor has been approved for patients with lymphoma and multiple myeloma who show poor PBSC mobilization, and its use is expected to increase the likelihood of successful ASCT. However, it is still difficult to define 'poor' mobilization because the total number of CD34+ cells can be influenced by the number of apheresis. There have been variable parameters to evaluate the extent of mobilization, such as cumulative apheresis yield as well as the number of CD34+ cells per apheresis. In addition, the total yield of CD34+ cells depends on the number of courses of apheresis, which is, in turn contingent on physicians' discretion. Recently, the Italian Group for Stem Cell Transplantation (GITMO) proposed consensus criteria for 'proven poor mobilizers' as follows: (a) circulating CD34+ cell peak of less than 20/µL up to 6 days after mobilization with G-CSF or up to 20 days after adequate mobilization such as using G-CSF 10 µg/kg if used alone or 5 µg/kg after chemotherapy, (b) less than 2.0×106 CD34+ cells per kg after fewer than three apheresis [4]. In Korea, use of plerixafor in combination with G-CSF is approved in patients with non-Hodgkin lymphoma and multiple myeloma for PBSC mobilization, and reimbursement is provided to those who have failed previous mobilization attempts with chemotherapy and G-CSF. However, the appropriate time for the initiation of plerixafor is still subject to ambiguity due to the lack of consensus on usable criteria for determining mobilization failure. Despite CD34+ PBSC count being considered the most powerful predictive factor of mobilization failure, the measurement of circulating CD34+ cells is not feasible in a majority of institutes in Korea. Therefore, at the recent meeting of the Consortium for Improving Survival of Lymphoma (CISL), the board members adopted a consensus definition of 'mobilization failure' as a count of less than 2.0×106 CD34+ cells/kg after three courses of apheresis. Thus, if the total number of CD34+ cells does not reach the minimum requirement for ASCT, the use of plerixafor should be considered, rather than continuation of apheresis with G-CSF. Furthermore, in specific patient populations which are expected to have low possibility of adequate cell yield such as elderly and heavily-pretreated patients, the board members of CISL discussed early administration of plerixafor. While the risk factors of mobilization failure have not yet been clearly identified, the recent GITMO working group proposed consensus criteria to define 'predicted poor mobilizers' as follows: (1) they failed a previous collection attempt (not otherwise specified); (2) they previously received extensive radiotherapy or full courses of therapy affecting PBSC mobilization; and (3) they met two of the following criteria: advanced disease (≥two lines of chemotherapy), refractory disease, extensive bone marrow involvement or cellularity <30% at the time of mobilization; age ≥65 years (4). A recent study on identifying prognostic factors for prescribing plerixafor-based PBSC mobilization showed that an age of 65 years, a diagnosis of non-Hodgkin's lymphoma, and treatment with four chemotherapy regimens were significantly associated with mobilization failure. Given the congruence between these prognostic factors and GITMO criteria of 'predicted poor mobilizers', it is evident that PBSC mobilization is impacted by the existence of risk factors and hence, the early use of plerixafor for high-risk groups should be carefully considered [5]. Further study is warranted to prevent mobilization failure by maximizing the benefit of plerixafor in Korean clinical setting. Plerixafor is a new class agent with a novel mechanism of action and has the potential to lead to a paradigm shift in PBSC mobilization and success of ASCT. In the era of plerixafor, considerable changes in clinical practices associated with PBSC mobilization can be expected in Korea.

Use of Plerixafor to Overcome Stem Cell Mobilization Failure: Long Term Follow up of Patients Proceeding to Transplant Using Plerixafor Mobilized Stem Cells

Abstract 4390 Background:Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods:Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results:Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion:Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures:Lum:Transtarget Inc: Equity Ownership, Founder of Transtarget. [Display omitted]

PLERIXAFOR IN POOR STEM CELL MOBILIZERS: THE BELGIAN COMPASSIONATE USE PROGRAM

Introduction: Currently available stem cell mobilizing regimens (G-CSF +/- chemotherapy) show high failure rates, especially in heavily pretreated patients. Plerixafor, a new stem cell mobilizing agent blocking the CXCR4-SDF-1 interaction, offers a new strategy for stem cell mobilization, especially in poor mobilizers. This study reports on the outcome of the Belgian compassionate use program (CUP).Materials and methods: Between July 2008 and July 2009, 14 Belgian transplant centres participated in plerixafor CUP. In total, 22 poor stem cell mobilizers were included. Patients who previously failed stem cell mobilization received a combination of G-CSF (morning of Day 1-5) and plerixafor (evening of Day 4). Apheresis was performed on Day 5. G-CSF, plerixafor and apheresis were continued until at least 2 × 106/kg CD34+ cells were obtained in a maximum of 3 collections.Results: A mean of 2 plerixafor administrations was needed to reach ≥ 2 × 106/kg CD34+ cells. The overall cumulative success rate (defined as the proportion of patients achieving a successful collection after a maximum of 3 apheresis days) was 64%. Half of the heavily pretreated patients (≥ 3 prior chemotherapy regimens) could be mobilized successfully. Patients who received ≤ 2 prior chemotherapy regimens mobilized successfully in 75% of the cases. Thirteen patients (59.1%) underwent autologous stem cell transplantation with normal neutrophil and platelet recovery times.Conclusion: For patients failing previous mobilization attempts, the combination of plerixafor and G-CSF is a successful mobilizing strategy, even in poor mobilizers who received ≥ 3 prior chemotherapy regimens.

Safety and Efficacy of Hematopoietic Stem Cell Remobilization with Plerixafor (Mozobil®) + G-CSF In Pediatric Patients with Malignant Disorders

AbstractAbstract 2245 Background:High dose chemo/radiotherapy followed by autologous hematopoietic stem cell (HSC) transplantation (HSCT) is indicated in several pediatric malignant disorders such as neuroblastoma and relapsed Hodgkin's disease. Ideally, 2–5 × 106 CD34+ cells/kg should be infused during autologous peripheral blood (PB) HSCT to support timely and durable engraftment and improve transplant outcomes. In patients who have received repetitive cycles of intensive chemotherapy, this target is not always achieved with standard mobilization regimens. Plerixafor, a novel CXCR4 antagonist, when combined with granulocyte colony-stimulating factor (G-CSF), can safely and predictably mobilize adequate numbers of CD34+ HSC to support transplantation in adult patients with myeloma and lymphoma. We report on the safety and efficacy of PB HSC mobilization with plerixafor + G-CSF in pediatric patients with cancer. Methods:This is a retrospective analysis of all children with various malignant disorders who were enrolled in the US plerixafor compassionate use program (CUP; NCT00291811). Patients who had previously failed HSC mobilization (defined as the inability to collect ≥2 x106 CD34+ cells/kg or achieve an adequate PB CD34+ cell count, typically ≥10 CD34+ cells/μl) with growth factor +/− chemotherapy were treated with plerixafor + G-CSF. The goal was to collect ≥2 × 106 CD34+ cells/kg for autologous HSCT. G-CSF (10μg/kg SC) was administered daily for 5 days. Plerixafor (0.24 mg/kg SC) was given in the evening on Day 4, ~11 hours prior to apheresis. Plerixafor, G-CSF and apheresis were repeated daily until ≥2 × 106 CD34+ cells/kg had been collected. Results:A total of 16 patients with non Hodgkin's lymphoma (3), Hodgkin's disease (1), CNS tumors (4), Ewing's sarcoma (4), neuroblastoma (2), osteogenic sarcoma (1) and desmoplastic small cell tumor (1) underwent the procedure. The median age was 14 years and 7 (44%) patients were male. In previous mobilization attempts, 5 patients failed to collect the minimum transplantable cell dose with a median yield of 0.44 x106 (range: 0.17–2.2 × 106) CD34+ cells/kg. Apheresis was never attempted in11 patients due to low PB CD34+ cell levels; median cells/μl was 1.0 (range, 0.01–12) in 9 patients with available data. Initial mobilization regimens included growth factor alone in 6 patients and growth factor + chemotherapy in 9 patients (data unavailable for 1 patient). When re-challenged for mobilization with plerixafor + G-CSF, 14 (88%) patients successfully collected ≥2 × 106 CD34+ cells/kg; this included all 4 (100%) patients with lymphoma and 10 (83%) patients with solid tumors. The median time to collect the target cell dose was 1.5 days (range 1–5 days). The median CD34+ cell yield from all patients was 3.5 × 106 cells/kg (range 0.96 – 9.80 × 106); patients with lymphoma and solid tumors collected a median of 7.2 (range 3.2 – 7.9) × 106 and 3.3 (range 0.96 –9.8) × 106 CD34+ cells/kg, respectively. Eleven (69%) patients proceeded to transplant including all 4 (100%) patients with lymphoma and 7 (58%) patients with solid tumors. One patient with neuroblastoma received a tandem transplant. The median infused cell dose was 4.18 × 106 CD34+ cells/kg (range 1.7 – 7.6 × 106). The median time to neutrophil and platelet engraftment was 14 and 33 days, respectively. Plerixafor-related adverse events were mostly mild, and observed in 5 (31%) patients. They included administration site reactions (4), vomiting (2), nausea (1) and oral paraesthesia (1). No patient experienced a serious adverse event. Conclusions:Treatment with plerixafor + G-CSF safely and effectively mobilized HSC in the majority of pediatric patients with malignant disorders after failure of standard mobilization with growth factor ± chemotherapy. Successful stem cell mobilization allowed consideration of autologous HSCT when indicated. Mobilization with plerixafor was safe and resulted in prompt engraftment. Many of these patients could not have proceeded to transplant without this intervention.Outcomes of plerixafor+ G-CSF remobilization in childrenNo. of Patients16Median age (range)14 (8–18)Gender, male (%)7 (44)Median CD34+ cells/kg × 106 collected (range)3.5 (0.96–9.80)No. of patients collecting ≥2 × 106 CD34+ cells/kg (%)14 (88)No. of patients proceeding to transplant (%)11 (69)Median days to neutrophil engraftment (range)14 (9–23)Median days to platelet engraftment (range)33 (12–86) Disclosures:Off Label Use: Plerixafor (Mozobil®), a hematopoietic stem cell mobilizer, is approved by the US FDA in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. McCarty: Genzyme, Amgen: Honoraria, Research Funding. Angell: Genzyme Corporation: Employment, Equity Ownership. Huebner: Genzyme Corporation: Employment, Equity Ownership.

Mobilization strategies in hard‐to‐mobilize patients with lymphoid malignancies

Depending on definitions and patient characteristics, 5-40% of patients with lymphoid malignancies are hard-to-mobilize. Several premobilization factors such as previous chemotherapy (CT), disease, marrow infiltration and platelet count at the time of mobilization influence the efficacy of CD34(+) cell mobilization. In general, however, prediction of hard-to-mobilize patient is difficult. Postmobilization factors especially low blood CD34(+) counts are important in clinical practice as we have now ways to enhance mobilization at this point. Plerixafor combined with granulocyte-colony stimulating factor (G-CSF) has significantly increased efficacy of remobilization in patients who have failed a previous mobilization attempt with a success rate of about 70%. Addition of plerixafor to G-CSF or more recently to a mobilization regimen consisting of CT + G-CSF is promising as blood CD34(+) counts can be increased three to fivefold to facilitate effective collection with less aphaeresis sessions. As plerixafor is expensive, development of practical algorithms for its use is important to make blood stem cell mobilization and collection more efficient in a cost-effective way. This review attempts to summarize current treatment strategies in hard-to-mobilize patients with lymphoid malignancies.

Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)—Polish compassionate use experience

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N = 23), non-Hodgkin’s lymphoma (N = 20), or Hodgkin’s lymphoma (N = 18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/μL (range of 0–121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0–4) aphereses were performed. A minimum of 2.0 × 106 CD34+ cells per kilogram of the patient’s body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67 × 106 CD34+ cells/kg b.w. (0–8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin’s lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers.

Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data

Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached ≥ 10 CD34+ cells per μL with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected ≥ 2 × 10⁶, average 3.0 ± 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1±1.2 (1.9-7.7) × 10⁶ CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 ± 0.8; 8-30) and platelets (day 15; 18.5 ± 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate.

Successful mobilization, harvest and transplant of peripheral blood stem cells using AMD3100 and G‐CSF following high dose craniospinal irradiation for medulloblastoma in a young child

Contemporary protocols for the treatment of malignant brain tumors such as medulloblastoma (MB) in children, often involve craniospinal irradiation (CSI) at diagnosis followed by serial courses of high dose chemotherapy and autologous hematopoietic stem cell support. Patients often require several pheresis procedures in order to collect sufficient stem cells for this type of treatment, particularly if they have already had CSI. We describe the successful mobilization, collection and subsequent transplant of a 7-year-old female with medulloblastoma after recent CSI using granulocyte colony stimulating factor (G-CSF) and the CXCR4 antagonist AMD3100 after a failed previous mobilization attempt using G-CSF alone.

Efficacy of Administration of Plerixafor (Mozobil®) at 5:00 PM for Stem Cell Mobilization (SCM) in Patients Receiving Autologous Stem Cell Transplant.

Abstract 3218Poster Board III-155 IntroductionIn the phase 3 clinical trials of plerixafor plus G-CSF for SCM, plerixafor was administered at 10:00 pm on days prior to apheresis. This dosing schedule is based on the peak level of CD34+ cells in the peripheral blood (PB) at 11-14 hours after administration; however PB CD34+ cell levels were elevated from 4-18 hours after plerixafor administration. Due to inconvenience in dosing plerixafor at 10:00pm, we took advantage of its pharmacodynamic profile and explored an alternative dosing schedule, giving plerixafor at 5:00 pm. Here, we report our initial experience with the efficacy of this schedule. Patients and MethodsBetween 01/09 & 08/09, 22 candidates for autologous stem cell transplant (13 female; mean age = 59, range 32-69; 9 MM, 11 NHL & 2 HD) received plerixafor plus G-CSF for SCM. Eight (4 female) were previous mobilization failures; 3 had failed G-CSF alone and 5 had failed chemotherapy + G-CSF; 2 had failed >1 mobilization. At the time of mobilization, 6 patients (27%) were in CR and 16 (73%) were in PR. Eight patients (36%) had disease in the bone marrow, 7 of these had MM and 1 had NHL. Of the 9 MM patients 3 (33%) had previous lenalidomide therapy. Nine patients (41%) had received >2 different chemotherapy regimens prior to mobilization; 2 of these had failed traditional mobilization with either G-CSF or chemo + G-CSF. Seven patients (32%) had, had previous radiation therapy, of whom 2 had failed traditional mobilization. Our mobilization protocol for autologous SCM consisted of G-CSF 10mcg/kg given at daily at 6:00 am beginning on day 1 and plerixafor 0.24mg/kg SQ x1 (0.16mg/kg if creatine clearance < 50ml/min) given daily at 5:00 pm in our Outpatient Clinic beginning on day 4. Apheresis began at 8:30 a.m. on the morning of day 5. The minimum collection goal was 2 × 106 CD34+cells/kg per transplant while the maximum goal was 4 × 106CD34+cells/kg per transplant. SCM and apheresis were stopped after 1 collection if the maximum goal was reached or after the minimum goal was reached on any subsequent day. ResultsAdministration of G-CSF plus 5:00 pm plerixafor resulted in a median PB CD34+ cell count in the morning of apheresis of 32.1 CD34+ cells/ml (range, 1.2-135.7). The median total apheresis yield was 4.83 × 106 CD34 cells/kg (range, 0.06-10.98 × 106) in a median of 2 days of apheresis (range, 1-4). Of the patients with multiple myeloma, 3/9 (33%) collected >6 × 106 CD34 cells/kg with a median time of 1.3 days, although per our protocol patients were stopped after 2 apheresis sessions if >4 × 106 CD34+ cells/kg had been collected. 2/22 patients (9%) failed a plerixafor mobilization. One of these had MM and had failed 2 previous traditional mobilization attempts; this patient reached the minimum collection goal after a second plerixafor mobilization attempt following a 3-week break. The other had received 4 previous chemotherapy regimens for NHL prior to mobilization. Nineteen patients (86%) had proceeded to transplant as of August 12th 2009, including the patient with a second plerixafor mobilization. The median days to neutrophils and platelet engraftment were 16 (range, 14-26) and 9 (range, 10-14) respectively. The side effect profile was similar to that described previously. ConclusionAn alternative dosing SCM regimen giving at 5:00 pm allowed >90% of the patients to collect the minimum CD34+cell dose necessary to proceed to transplantation. This dosing schedule is more convenient and ensures 100% compliance with plerixafor dosing. DisclosuresTornatta:Genzyme: Consultancy, Speakers Bureau. Off Label Use: Plerxiafor is a chemokine recpeptor antagonist approved for use in pts with MM and NHL for mobilization of stem cells for autologous transplant. Our information includes patients with HD who were mobilized using plerxafor for stem cell mobilization and ultimately autologous stem cell transplantation. Fung:Genzyme: Consultancy, Speakers Bureau.

Peripheral Stem Cell Mobilization with Chemotherapy + G-CSF Priming in a Large Series of Patients with Lymphoma Candidates to Autologous Transplantation. An Analysis of Baseline and Ongoing Predictors of Failure or Suboptimal Stem Cell Collection.

Abstract 2149Poster Board II-126 BackgroundAutologous stem cell transplantation (ASCT) is a potentially curative treatment for lymphoma. Adequate stem cell (SC) collection is possible in the majority of cases but poor mobilization remains a major issue in some patients (pts). New agents were recently developed which may improve the rate of SC mobilization. AimsA retrospective analysis was conducted on a large series of lymphoma pts candidates to ASCT in order to identify factors influencing SC mobilization outcome. Potential early markers of poor mobilization were also evaluated. Patients and methodsA total of 415 attempts of PBSC collection consecutively performed at 7 Italian centres in 388 pts affected by lymphoma were analyzed. Their median age was 52. A collection of less than 2×106 CD34+ cells/kg was defined as “mobilization failure” and of more than 5×106 CD34+ cells/kg as “good mobilization”. The following parameters were analysed for correlation with mobilization outcome: lymphoma diagnosis, disease status at mobilization, type of mobilizing chemotherapy, bone marrow infiltration at collection, n° of previous lines of therapy, prior use of fludarabine, alkylating agents or radiotherapy. The ratio between circulating CD34+cells/nL and total WBC/μL on the first day of CD34+ count (SCratio) was also analysed, trying to predict mobilization failure. Both univariate and multivariate statistical analyses were performed with SPSS package 13.0. ResultsLymphoma diagnosis was diffuse large B cell/Burkitt in 38%, follicular in 10%, mantle in 13%, Hodgkin in 26%, T or NK/T in 6%, and other in 7% of cases. Disease status at apheresis was CR in 25%, chemosensitive in 49% and refractory in 26%. Mobilization was attempted during first-line therapy in 14%, in 37% during second-line and in 26% at third- or subsequent lines of therapy. Fludarabine, alkylating agents and extended-fields radiotherapy had been used prior to mobilization in 5%, 73% and 13% of cases respectively. Marrow infiltration by lymphoma was present in 17,7% and 7,7% of patients had failed a prior mobilization attempt.In 99% of cases (411/415) mobilizing therapy included chemotherapy and G-CSF. Two pts received AMD3100 and 2 G-CSF. Several chemotherapy programs were used for mobilization. For analysis purposes they were grouped as follows: single-agent cyclophosphamide (CTX) in 62 (15,1%); high-dose cytarabine, either single agent or in combination (HD-ARAC) in 143 (34,8%), etoposide-containing regimens in 119 (30,0%), and platinum containing regimens in 108 cases (26,3%).Mobilization failure occurred in 14% (59/415) whereas a good mobilization was obtained in 72% of cases. At univariate analysis mobilization failure was significantly associated with the use of single-agent CTX as mobilizer (p=0.000), with the n° of prior lines of treatment (p=0.006) and with failure of a previous mobilization attempt (p=0.000) whereas a diagnosis of follicular lymphoma (FL) was associated with a reduced risk of mobilization failure (p=0.007). Multivariate analysis confirmed FL as protective factor for mobilization failure (p=0.008) and single agent CTX and a higher n° of prior treatment lines as negative predictive factors (p=0.000 and 0.033 respectively).A “good mobilization” was significantly predicted at univariate analysis by HD-ARAC use as mobilizer (p=0,004) whereas single-agent CTX (p=0.000), n° of prior lines of therapy (p=0.005), prior fludarabine (p=0.035) or alkylating agents (p=0.003) were adverse predictors. Multivariate analysis confirmed HD-ARAC as independent predictive factor for good mobilization (p=0.031) and single-agent CTX and n° of prior lines of therapy as independent negative predictive factors (p=0.000 and 0.003 respectively). A SCratio of less than 10 on the first day of CD34+ count was associated with an increased risk of poor mobilization (p=0.000 risk estimate 0.638). ConclusionsIn this large series of pts with lymphoma the standard policy of SC mobilization was the use of chemotherapy + G-CSF. Nevertheless collection failed in a significant proportion of cases (14 %) and only 72% of cases reached an optimal SC collection. Predictive factors for mobilization outcome included disease and treatment history, type of lymphoma and type of mobilizing chemotherapy. These data provide the framework to rationally explore the use of new mobilizing agents in patients with lymphoma undergoing SC mobilization with chemotherapy and G-CSF. Disclosures:No relevant conflicts of interest to declare.

Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience

Auto-SCT has been shown to be a potentially curative treatment for a variety of hematological malignancies. Auto-SCT is dependent on the successful mobilization and collection of hematopoietic stem cells to ensure engraftment. The inability to mobilize sufficient number of hematopoietic stem cells using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative auto-SCT. Plerixafor (AMD3100; Mozobil), a novel bicyclam antagonist of the SDF-1alpha/CXCR4 complex, has been reported previously to augment PBSC mobilization in patients undergoing their first planned stem cell mobilization and collection attempt. In our experience, 17 of 20 patients otherwise eligible for auto-SCT who failed previous mobilization attempts had successful mobilization of CD34(+) hematopoietic stem cells with one apheresis procedure, and an additional patient required two aphereses procedures, when treated with the combination of plerixafor and G-CSF on a compassionate use protocol available at our institution.

Intermediate Dose Ara-C Followed by G-CSF: An Effective and Predictable Mobilization Regimen in Hematological Malignancies.

High dose (HD) chemotherapy followed by peripheral blood stem cell (PBSC) is widely used in the management of hematological malignancies and chemosensitive solid tumors. Different strategies of PBSC mobilization have been described, but currently the standard approach has not been established. Satisfactory results have been obtained by different chemotherapy schedules followed by haemopoietic growth factors: particularly HD Cyclophosphamyde or HDAra-C have a well known high mobilizing activity. With the intention to minimize hematological toxicity due to HD chemotherapy we performed this study to evaluate the mobilizing efficacy of intermediate dose Ara-C (IDAra-C).Methods: Pts with haematological malignancies received as mobilization treatment Ara-C 800 mg/m2 every 12 h for 6 doses followed by G-CSF 300 μg/d starting day +3 from the end of treatment until completion of leukapheresys (LP). CD34+ cells count was performed from day + 9. Failure of mobilization was defined as a persistent CD34+ cells count <10/μL. All pts reaching >10/μL CD34+ underwent LP. Pts not reaching the target of 2.5 x 106/kg CD34+ were considered as low mobilizer.Results: 98 pts, median age 56 y (range 27–70), underwent priming with IDAra-C. Disease characteristics are listed in table 1. All but 5 pts presented bone marrow involvement at diagnosis. Sixty-nine pts had previously received fludarabine, 56 anthracyclines and 30 alkilating agents. Thirty-three of the 98 pts had been considered low mobilizer or had failed a previous mobilization attempt, with HDAra-C in 20 cases A successful mobilization (threshold level >2.5 x 106/kg CD34+) was obtained in 73 pts (74,5%) (9/14 NHL, 42/43 CLL, 6/7 MM, 16/34 AML) with a median collection of 12,34 x 106/kg CD34+ (range 2,57–76,5). The peak value of CD34+ cells in the peripheral blood was achieved after a median of 13 d (range 10–19) from the end of therapy and a median of 1 LP (range 1–3) was required for a target collection. An adequate harvest was also observed among 17 of the 33 (51.5%) pts failing a previous mobilization attempt. After IDAra-C the median time to reach PMN >1000/μL and PLT >50000/μL was of 6 and 8 days respectively. There were no treatment-related deaths. During neutropenia we recorded 25 episodes of FUO, 9 infections microbiologically documented and 2 infections clinically documented. Median days temperature > 38°C was 2 (range 1–6). Extraematological toxicity consisted of: 1 gastrointestinal bleeding WHO III and 1 episode of atrial fibrillation. Overall 39 pts have been transplanted so far; median days for PMN >500/μL and PLT >50000/μL engraftment was of 9 and 12 d respectively. In conclusion IDAra-C and sequential G-CSF allowed predictable and efficient PBSC harvest in a limited number of leukapheresis session. Hematological recovery was rapid and toxicity manageable. These data confirm, in a larger series, the high mobilization activity of IDAra-C in CLL as previously reported. Moreover satisfactory efficacy has been observed in pts failing previous mobilization attempt with alternative regimen. This approach should be considered as an effective way to exploit a known mobilizing activity of Ara-C minimizing toxicity.Table 1Disease characteristicsAMLNHLCLLMMToTCR32335373CR > 123−−5PR−2−24nPR−−6−6SD−1124PD/RELAPSE−51−6Tot341443798median time from last treatment (months)2,02,34,32,63,4

Ancestim (recombinant human stem cell factor, SCF) in association with filgrastim does not enhance chemotherapy and/or growth factor-induced peripheral blood progenitor cell (PBPC) mobilization in patients with a prior insufficient PBPC collection.

Up to a third of autologous transplantation candidates fail to mobilize hematopoietic progenitors into the peripheral blood with chemotherapy and/or growth factor treatment, thus requiring innovative mobilization strategies. In total, 20 cancer patients unable to provide adequate PBPC products after a previous mobilization attempt were treated with ancestim (20 microg/kg/day s.c.) and filgrastim (10 microg/kg/day s.c.). In 16 patients, the pre-study mobilization was with filgrastim alone. Eight patients underwent single large volume leukapheresis (LVL) and 12 multiple standard volume leukaphereses (SVL) in both mobilizations. Pairwise comparison of peripheral blood CD34(+) cell concentrations on the day of first leukapheresis failed to document synergism - median CD34(+)/microl of 3.2 (<0.1 to 15.4) and 4.5 (1-28.56) for the pre-study and on-study mobilizations (P = 0.79, sign test), and 4.2 (<0.1-15.4) and 5 (1-28.56), respectively, for the 16 patients previously mobilized with filgrastim alone (P = 1, sign test). The number of CD34(+) cells/kg collected per unit of blood volume (BV) processed was similar in both mobilizations - median 0.1 x 10(6)/kg/BV and 0.09 x 10(6)/kg/BV, respectively (P = 1, sign test). In this phase II study, the combination of ancestim and filgrastim did not allow adequate PBPC mobilization and collection in patients with a previous suboptimal PBPC collection.