scholarly journals Outpatient Stem Cell Mobilization with Intermediate-Dose Cyclophosphamide Is a Safe and Effective Procedure

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5734-5734 ◽  
Author(s):  
Alessandra Pompa ◽  
Anna Ines Gregorini ◽  
Francesca Guidotti ◽  
Maria Cecilia Goldaniga ◽  
Francesca Gaia Rossi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Cranial Nerve ◽  
The Other ◽  
Stem Cell Mobilization ◽  
Cranial Nerve Deficit ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Grade 3 ◽  
Intermediate Dose

Abstract Background In younger and fit multiple myeloma (MM) patients (pt), autologous stem cell transplantation (ASCT) remains the gold standard treatment. Mobilization chemotherapy is usually administered in an inpatient regimen and Cyclophosphamide (CY) at different doses is the most used chemoterapy for collecting peripheral blood stem cells (PBSC) in MM. Clinical trials have demonstrated that intermediate dose CY (3 and 4 g/m2, ID-CY) combined with G-CSF, is an efficient mobilizing regimen with less toxicity compared with high dose CY (7 g/m2, HD-CY) in term of neutrophil recovery, thrombocytopenia, need of transfusions and IV antibiotics. (Fitoussi et al, BMT 2001; Goldschmidt et al, BMT 1996). Objective To evaluate the safety of mobilization therapy administered in an outpatient regimen, with the prospect to lower costs and minimize patient inconvenience, maintaining an optimal yield. Methods 92 pt with newly diagnosed MM underwent outpatient stem cell mobilization between 2002 and 2016 with CY 3 g/m2 (82%) or 4 g/m2 (18%) + G-CSF after induction therapy with bortezomib-based (79%) or VAD-like (21%) regimens. No antibiotics prophylaxis was routinely used. Day 0 was defined as the CY infusion day. CY was administered in 2-4 consecutive 1h infusions (depending on total dose). Hyper-hydration (3.5/4 l), antiemetics and the uroprotectant Uromitexan were began IV 1 hour before CY infusion. Subsequently, Uromitexan was continued at home orally in the next 12h. Furthermore, the patient was advised to drink 2.5/3 l of water in the next 24h. G-CSF 10 mcg/Kg was started by day +5 and continued until completion of apheresis. Blood count was monitored at day + 4 and daily from day +7. CD34+ cells were counted on peripheral blood by day 7; apheresis was started at leukocyte rise and with a value of at least 20 CD34+/μl. Number of apheresis depended on the number of CD34+ cells collected to obtain al least 4x106 CD34+/Kg. Results Median age at diagnosis of was 56y (range 34-68). MM isotype was IgA, IgG and micromolecular respectively in 18%, 58% and 24%. Prior MGUS was present in 37 cases (43%). LDH was elevated in 7 pt (11%), whereas ISS was 1/2/3 in 47%/30%/23%. Bone disease was detectable in 74% of pt, with 56% having 3 or more osteolysis. Median bone marrow plasma cell at diagnosis was 60% (range 10-95%). Pt received induction with bortezomib-based regimens (79%) or chemoterapy, mostly VAD (21%). 8 pt (9%) required second line therapy before mobilization. Response prior of mobilization was CR/sCR in 15%, VGPR in 59%, PR in 24%, and SD in 2%. Stem cell collection was successful in 98% of pt, with a median CD34+ harvest of 9.8x106/Kg. Chemotherapy was very well tolerated. Most frequently observed adverse events (AEs) were nausea and vomiting of grade 1-2. 2 pt experienced cystitis (one grade 1, one grade 2), 2 pt infections, 2 pt hyperthermia regressed rapidly without therapy, 1 patient diarrhea. 3 pt had neurological symptoms: in 2 cases they were aspecific (headache, instability); the other case presented a sudden appearance of 7th cranial nerve deficit at the end of mobilization chemotherapy infusion with negative imaging and successively regressed in few hours, interpreted as transient ischemic attack not correlated with Cy. Only 2 patient required hospitalization for AEs: 1 patient for fever grade 3 without microbiological findings, rapidly regressed with IV antibiotics; the second one for 7th cranial nerve deficit. These were the only grade 3 AEs, no grade 4 AEs verified. There were no other significant AEs related to chemotherapy. All pt except 2 proceeded to stem cell harvest and reached CD34+ target, but 5 pt required administration of Plerixafor on demand. The 2 pt not reaching CD34+ target successfully mobilized afterwards, 1 with different chemoterapy and the other with G-CSF and Plerixafor. After mobilization, 88 pt proceeded to single (45%) or double (55%) ASCT. Conclusion In conclusion, outpatient mobilization with ID-CY appears to be an efficient and safe procedure, with minimal and manageable side effects and low rate of hospitalization. Outpatient mobilization could ameliorate the quality of life of pt and reduce costs, avoiding or minimizing the hospitalization rate, without compromising the safety profile and the success of PBSC collect. Disclosures No relevant conflicts of interest to declare.

scholarly journals G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5823-5823
Author(s):  
Ahmad Antar ◽  
Zaher Otrock ◽  
Mohamed Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Nabila Kreidieh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity. Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups. Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16). Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Comparison of CXCR-4 and Adhesion Molecule Expression in Healthy Bone Marrow with Expression in Bone Marrow and Peripheral Blood of Patients Receiving G-CSF Plus AMD3100.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1974-1974
Author(s):  
Uta Oelschlaegel ◽  
Martin Bornhaeuser ◽  
Frank Kroschinsky ◽  
Gerhard Ehninger ◽  
Uwe Platzbecker
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Adhesion Molecules ◽  
Peripheral Blood ◽  
Surface Expression ◽  
Stem Cell Mobilization ◽  
Qualitative And Quantitative ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract It is known that the crosstalk between adhesion molecules, bone marrow microenvironment, and cytokines facilitates the multi step process of stem cell mobilization from bone marrow to peripheral blood. A combination of G-CSF plus AMD3100 - a CXCR-4 antagonist - has been shown to be safe and efficient in stem cell mobilization of healthy donors and cancer patients. Nevertheless, data predicting the efficacy of this approach are still missing. The present study investigated the correlation of the expression of CXCR-4 (CD184) and adhesion molecules with the kinetics and efficacy of stem cell mobilization in nine patients with Multiple Myeloma (MM) or NHL, respectively. Steady-state mobilization was performed using a combination of G-CSF (Filgrastim, 10μg/kg/d, 8 am) for 4 days followed by AMD3100 (240μg/kg) on day 4 at 10pm. Autologous aphereses were started on day 5. Bone marrow and peripheral blood (PB) before AMD3100 application (day 4) and PB on day 5 were investigated with a 4-color flow cytometric procedure. Bone marrow aspirates of healthy donors (n=20) served as control. The qualitative (%) and quantitative (mean fluorescence intensity, [MFI]) antigen expression of CXCR-4 in relation to CD34 was assessed as well as the expression of certain adhesion molecules including LFA-1, PECAM-1, VLA-1, L-selectin and CD44. First, the median percentage of CXCR-4 surface expression in healthy bone marrow was significantly higher (92%; range: 52 – 99%) than in patients bone marrow (70%; 30 – 88%; p=0.002), PB before AMD3100 (87%; 35 – 97%; p=0.050) and on day 5 (17%; 2 – 74%; p<0.001), whereas cytoplasmic expression was comparable (91%; 53 – 95%) in all cell compartments. The median quantitative CXCR-4 surface expression was significantly decreased in PB on day 5 compared to pre AMD3100 (14 vs. 95; p=0.003). Furthermore, the qualitative expression of LFA-1 and the quantitative expression of LFA-1, PECAM-1, VLA-1, and CD44 were also downregulated in response to AMD3100 (p<0.010). Second, a median of 63/μl (range: 15 – 132/μl) CD34+ cells was measured in the PB on day 5. Thus, a high absolute count of CD34+ cells in the PB on day 5 significantly correlated with lower qualitative and quantitative CXCR-4 expression in the same material (r=0.833; p=0.015). Evaluating CXCR-4 expression in bone marrow, PB before AMD3100 and on day 5 no significant correlation to CD34+ counts could be detected. However, there was one very poor mobilizing patient (15/μl CD34+ cells on day 5) in whom the quantitative CXCR-4 expression in the bone marrow was significantly higher than the median of all patients (MFI 95 vs. 26). Furthermore, some of the adhesion molecules (L-selectin, VLA-4, and CD44) showed a rather positive correlation with CD34 count. In summary, these preliminary data suggest that the amount of CD34+ cells in the peripheral blood after G-CSF plus AMD3100 application seems to be negatively correlated with CXCR-4 expression. A higher quantitative CXCR-4 expression in the bone marrow pre AMD3100 might predict a lower mobilization efficacy.

Bortezomib Given in Sequence with Anthracycline and Thalidomide-Containing Regimens Does Not Adversely Affect Stem Cell Mobilization and Engraftment in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 541-541
Author(s):  
Geoffrey L. Uy ◽  
Nicholas M. Fisher ◽  
Steven M. Devine ◽  
Hanna J. Khoury ◽  
Douglas R. Adkins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Dose Melphalan

Abstract Bortezomib (VELCADE®) is a selective inhibitor of the 26S proteasome proven to be safe and effective in the treatment of relapsed or refractory multiple myeloma (MM). While high-dose chemotherapy with autologous hematopoietic stem cell transplant (AHSCT) remains the standard of care, there is considerable interest in incorporating bortezomib into the initial treatment of MM. However, the role of bortezomib in frontline therapy for MM will depend in part on its effects on subsequent stem cell mobilization and engraftment. We conducted a pilot study of bortezomib administered pretransplant followed by high-dose melphalan with AHSCT. Two cycles of bortezomib 1.3 mg/m2 were administered on days 1, 4, 8, and 11 of a 21-day treatment cycle. One week after the last dose of bortezomib, stem cell mobilization was initiated by administering filgrastim 10 mcg/kg/day subcutaneously on consecutive days until stem cell harvest was completed. Stem cell collection began on day 5 of filgrastim via large volume apheresis (20 L/day) performed daily until a minimum of 2.5 x 106 CD34+ cells/kg were collected. Patients were subsequently admitted to the hospital for high-dose melphalan 100 mg/m2/day x 2 days followed by reinfusion of peripheral blood stem cells 48 hours later. Sargramostim 250 mcg/m2/day subcutaneously was administered starting day +1 post-transplant and continued until the absolute neutrophil count (ANC) ≥ 1,500/mm3 for 2 consecutive days. To date, 23 of a planned 40 patients have been enrolled in this study with 19 patients having completed their initial therapy with bortezomib followed by AHSCT. Patient population consists of 16 male and 7 female patients with the median age at diagnosis of 58 years (range 38–68). Myeloma characteristics at diagnosis were as follows (number of patients): IgG (16), IgA (7) with stage II (9) or stage III (14) disease. Prior to receiving bortezomib, 11 patients were treated with VAD (vincristine, Adriamycin and dexamethasone) or DVd (Doxil, vincristine and dexamethasone), 5 patients with thalidomide and 5 patients with both. Two patients did not receive any prior chemotherapy. All patients successfully achieved the target of 2.5 x 106 CD34+ cells/kg in either one (15/19 patients) or two (4/19 patients) collections with the first apheresis product containing a mean of 5.79 x 106 CD34+ cells/kg. Analysis of peripheral blood by flow cytometry demonstrated no significant differences in lymphocyte subsets before and after treatment with bortezomib. Following AHSCT, all patients successfully engrafted with a median time to neutrophil engraftment (ANC ≥ 500/mm3) of 11 days (range 9–14 days). Platelet engraftment (time to platelet count ≥ 20,000/mm3 sustained for 7 days without transfusion) occurred at a median of 12 days (range 9–30 days). Eleven patients were evaluable for response at 100 days post-transplant. Compared to pre-bortezomib paraprotein levels, 3 patients achieved a CR or near CR, 7 maintained a PR while 1 patient developed PD. We conclude that pretransplant treatment with 2 cycles of bortezomib does not adversely affect stem cell yield or time to engraftment in patients with MM undergoing AHSCT. Updated results and detailed analysis will be available at the time of presentation.

A Retrospective Evaluation of the Impact of Pre-Emptive Plerixafor Administration on Collection Efficiency in Patients with Myeloma Undergoing Stem Cell Mobilization

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5740-5740 ◽  
Author(s):  
Leslie A. Andritsos ◽  
Ying Huang ◽  
Tao Fan ◽  
Keith Huff ◽  
Ed Drea ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Research Funding ◽  
Collection Efficiency ◽  
Treatment Algorithm ◽  
Stem Cell Mobilization ◽  
Cell Dose ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
The Impact

Abstract Background: High dose melphalan with autologous stem cell support (aSCT) remains one of the most beneficial therapies for myeloma. However, this therapy may be limited by the ability to collect a minimum CD34+ cell dose of 2.0 × 106/kg. Failure to collect an adequate CD34+ cell dose leads to significantly increased costs and treatment delays. Plerixafor (PL) is a mobilization agent which reversibly inhibits binding of SDF-1 to the chemokine receptor CXCR4, resulting in mobilization of hematopoietic progenitor cells. Phase 3 studies demonstrate that administration of PL significantly improves the likelihood of successful CD34+ cell collection compared to G-CSF alone (Dipersio, Blood 2009) in patients with myeloma and NHL. In order to improve collection efficiency, our center began a policy of PL administration to all myeloma patients undergoing collection pre-emptively on the evening prior to Day 1 of collection. Herein we evaluate the outcomes of that policy change when compared to patients who received PL on Day 1 (D1) of collection according to a treatment algorithm which evaluated peripheral blood (PB) CD34+ cell number as well as D1 CD34+ cell dose collection. Methods: Patients with myeloma undergoing mobilization who received PL during their treatment course were eligible. Patients were categorized according to timing of administration to either pre-emptive (P-PL) or standard (S-PL), which was given according to a treatment algorithm on day 1 of collection based on CD34+ cell dose. Patients were evaluated for total CD34+ dose procured, number of apheresis procedures, risk factors for poor mobilization and collection (age, prior therapies, and DM), and pre-emptive vs. standard PL. A multivariable logistic regression model was built to predict the ability to achieve minimum collection goal. Results: From 2009 to 2014, 299 patients received PL during stem cell mobilization and were available for evaluation. Of these, 241 received P-PL and 58 received S-PL. There were no significant differences between patient groups with respect to sex, age, race, KPS, ISS score, CMI, # of prior therapies, prior lenalidomide, DM-2, or disease status at the time of transplant. As expected, patients who received P-PL had significantly better collection. Patients who received P-PL had a median CD34+ peripheral blood cell count (absolute) on the day before collection of 21 (range 0-162) vs. 8 for S-PL (range 3-90, p<0.0001). Median total CD34+ cell dose collected on D1 of collection was 6.75 in the P-PL group vs 1.96 in the S-PL group (p<0.0001). There was no significant difference in collection efficiency for days 2 and 3 of collection between the groups. There was no difference between the numbers of doses of PL received, with both groups receiving a median of 1 dose (range 1-3 for both). The majority of P-PL patients completed collection in 1-2 collections (99%) vs. 64% for S-PL (p<0.0001). With respect to engraftment, there were no differences between the groups for platelet engraftment to 20,000/mcl, however patients in the P-PL group had a significantly longer ANC engraftment time (11 vs. 10 days, p<0.0001), possibly explained by a change in post-transplant filgrastim administration to day +7 which occurred during that time; these patients also had a longer hospital stay, possibly for the same reason. On univariable analysis, pre-emptive PL was the only factor significantly associated with likelihood of collection of at least 2.0 x 106 CD34+ cells/kg on first collection (p<0.0001). On multivariable analysis, factors significantly associated with collection of at least 2.0 x 106 CD34+ cells/kg on D1 included P-PL (p<0.0001), CR or PR at the time of collection (p=0.03), and DM-2 (p=0.05). Two patients in the P-PL group failed to collect 2.0 x 106 CD34+ cells/kg by day 4 of collection despite this up-front strategy; the cell doses collected were 1.91 x 106 and 1.99 x 106. Conclusions: Up-front administration of PL significantly enhances collection efficiency, with the majority of patients (77%) completing collection in one day. Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Fan:Sanofi: Employment. Drea:Sanofi: Employment. McBride:Sanofi: Research Funding.

scholarly journals Plerixafor for Autologous Peripheral Blood Stem Cell Mobilization in Patients Previously Treated with Fludarabine or Lenalidomide

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1932-1932
Author(s):  
Florent Malard ◽  
Nicolaus Kröger ◽  
Ian H Gabriel ◽  
Kai Hübel ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Non Hodgkin Lymphoma ◽  
Cd34 Cells ◽  
Previously Treated ◽  
Cell Mobilization ◽  
Autologous Hsct

Abstract Abstract 1932 High dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). At present, G-CSF-mobilized peripheral blood stem cells (PBSCs) are the preferred stem cell source for autologous HSCT. Fludarabine and lenalidomide are essential drugs in the front line treatment of NHL and MM respectively. Data suggests that fludarabine and lenalidomide therapy may have a deleterious effect on stem cell mobilization. Prior to the drug approval in Europe, a plerixafor compassionate use program (CUP) was available from July 2008 to August 2010 to provide access to the drug for patients with MM or lymphoma who had previously failed a mobilization attempt, and who were not eligible for another specific plerixafor trial. In the European CUP, 48 patients (median age 57 years; range, 36–69), previously treated with fludarabine (median 5 cycles; range, 1–7 cycles) were given plerixafor plus G-CSF for remobilization following a primary mobilisation attempt. All 48 patients had a diagnosis of NHL. The overall median number of CD34+ cells collected was 2.3×106 /Kg (range, 0.3–13.4). The minimum required number of CD34+ cells (≥2.0×106 per kg) was collected from 58% of patients, while only 3 patients (6%) collected ≥5.0×106 CD34+ cells. The collection target of 2.0×106/Kg was reached in a median of 2 apheresis sessions (range, 1–3). Thirty-five patients (median age 57 years; range, 34–66), previously treated with lenalidomide (median 5 cycles; range, 1–10 cycles) were given plerixafor plus G-CSF for remobilization. All patients the 35 patients had MM. The overall median number of CD34+ cells collected was 3.4×106/Kg (range, 1.1–14.8). The minimum required number of CD34+ cells (≥2.0×106 per kg) was collected from 69% of patients, including 12 patients (34%) who were able to collect ≥5.0×106 cells/Kg. In the Len group, 7 patients (20%) had received a prior autologous HSCT before salvage mobilization with plerixafor. Both targets were reached with a median of 2 apheresis sessions (range, 1–4). In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for large prospective studies evaluating the efficacy of plerixafor for frontline mobilization in this subgroup of patients.Table 1.Study population characteristicsCharacteristic (%)Fludarabine (N=48)Lenalidomide (N=35)Patient age, median (range)57 (36–69)57 (34–66)Patient gender    Male26 (54)18 (51)    Female22 (46)17 (42)Fludarabine or Lenalidomide cycles, median (range)5 (1–7)5 (1–10)Diagnosis and disease statusIndolent NHL48 (100)0 (0)Multiple myeloma0 (0)35 (100)Previous chemotherapy: number of lines, median (range)3 (1–6)4 (1–9)Previous autograft    Yes07 (20)    No43 (90)20 (57)    Data missing5 (10)8 (23)Radiotherapy    Yes5 (10)3 (9)    No36 (75)24 (68)    Data missing7 (15)8 (23)Mobilization strategy with plerixafor    Steady-state GCSF mobilization38 (79)27 (77)    Chemotherapy+GCSF mobilization10 (21)8 (23)No. of patients collected44 (92)34 (97)CD34+ cells collected per Kg, median (range)2.3 (0.3–13.4)3.4 (1.1–14.8)No. of patients who reached ≥ 2.106 CD34+28 (58)24 (69)No. of apheresis days to reach ≥ 2.106 CD34+2 (1–3)2 (1–4)No. of patients who reached ≥ 5.106 CD34+3 (6)12 (34)No. of apheresis days to reach ≥ 5.106 CD34+2 (1–3)2 (1–3)NHL, non-Hodgkin lymphoma Disclosures: Mohty: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Allogeneic Stem Cell Transplantation with Peripheral Blood Stem Cells Mobilized by Pegylated-G-CSF.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1970-1970
Author(s):  
Geoff Hill ◽  
Edward S. Morris ◽  
Maddona Fuery ◽  
Cheryl Hutchins ◽  
Jason Butler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Function ◽  
Ideal Body Weight ◽  
Stem Cell Mobilization ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
12Mg Dose

Abstract The mobilization of stem cells with pegylated-G-CSF (peg-G-CSF) modulates regulatory T cell and NKT cell function, separating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects in animal models. We have initiated a phase I/II study to analyse the feasibility of mobilizing stem cells from sibling donors with peg-G-CSF and their ability to restore hematopoiesis in HLA matched transplant recipients who have received myeloablative conditioning. Results were compared to a cohort of donors mobilized with standard G-CSF at 10ug/kg/day (n=19). The administration of 6mg of peg-G-CSF (n=6) resulted in suboptimal stem cell mobilization with a peak peripheral blood CD34+ count of 29 ± 4/uL. Apheresis 4 days after peg-G-CSF administration yielded 2.7 ± 0.3 x106 CD34+ cells/kg recipient ideal body weight and all patients required a second collection on day 5 to yield a total of 4.0 ± 0.5 x106 CD34+ cells/kg recipient weight. Following escalation of the dose to 12mg (n=9), the peak CD34+ count was 109 ± 13/uL and all donors collected sufficient stem cells for transplantation in a single apheresis (9.8 ± 1.7 x106 CD34+ cells/kg recipient weight). The 6mg dose of peg-G-CSF was significantly inferior to standard G-CSF for stem cell mobilization (P<0.01) while the 12mg dose was at least equivalent (P=0.07). Bone pain was similar between the 6mg and 12mg cohorts and to that seen with standard G-CSF. However, in addition to the expected rises in serum ALP and LDH, transient rises in hepatic transaminases were noted 5 to 12 days after peg-G-CSF administration in 7 of 9 donors receiving the 12mg dose. One donor developed NCI grade 3 hepatic toxicity and splenomegaly. After allogeneic transplantation of peg-G-CSF mobilized grafts (Cy/TBI conditioning in 13 of 14 recipients), median neutrophil and platelet engraftment occurred on days 18 and 14 respectively and was identical to that seen with grafts mobilized by standard G-CSF. With a median follow up of 165 days (range 55–532), the incidence of grade II-IV and grade III/IV acute GVHD is 50% and 21% respectively. No patients have relapsed to date and overall survival is 86%. The mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12mg appears the optimal dose. Further data are required to more closely analyse the effect of peg-G-CSF on donor liver function and the ability of stem cell grafts to separate GVHD and GVL effects. Figure Figure

Efficacy of Plerixafor Administered At 5:00PM for Stem Cell Mobilization in Lymphoma and Myeloma Patients Undergoing Autologous Stem Cell Transplant,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4061-4061
Author(s):  
Jennifer Tornatta ◽  
John J. Maciejewski ◽  
Sunita Nathan ◽  
Bruce Mcleod ◽  
Sridevi Palaparthy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Cell Transplant ◽  
Dosing Schedule ◽  
Pharmacodynamic Profile ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 4061 Background: High-dose chemotherapy and/or radiotherapy are effective treatment strategies for patients with life-threatening hematologic malignancies. A critical step to the success of transplantation is achieving adequate mobilization of CD34+ stem cells from the bone marrow into the peripheral blood to provide sufficient cell yield after apheresis for the transplant. Plerixafor combined with granulocyte colony-stimulating factor (G-CSF) has proven efficacious in mobilizing CD34+ stem cells in patients with lymphoma and myeloma prior to autologous stem cell transplantation. In 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 updated experience with the efficacy of this schedule. Method: We performed a retrospective study using our Stem Cell Harvest database. A total of 58 patients (31 lymphoma, 27 myeloma) underwent mobilization with G-CSF + plerixafor, either as front-line (n=51) or as salvage (n=7) mobilization strategies between February 2009 through May 2010. Mobilization consisted of G-CSF 10 μg/kg SC administered daily at 6:00 am day 1 through 4 plus plerixafor 0.24 mg/kg SC given once daily at 5:00 pm in an outpatient clinic beginning on day 4. For patients with renal impairment (ie, creatinine clearance ≤50 mL/min), the dose of plerixafor was lowered by a third to 0.16 mg/kg. Daily apheresis began at 8:30 am on the morning of day 5 and continued for up to 4 days, with a minimum collection goal defined as ≥ 2 × 106 CD34+ cells/kg for lymphoma patients and ≥ 4 × 106 CD34+ cells/kg for myeloma patients. Mobilization with G-CSF plus plerixafor and apheresis were halted once the minimum goal was reached between day 2 and 4 of apheresis, or after a single collection achieved the optimal goal which was defined as ≥ 4 × 106 (lymphoma) or ≥ 8 × 106 (myeloma) CD34+ cells/kg. The mobilization strategy was considered a failure if patients did not reach the minimum CD34+ cell collection goal within the 4 days of apheresis. Results: G-CSF + plerixafor mobilization yielded a median 5.13 × 106 CD34+ cells/kg (range, 0.06–25.8) in a median of 2 apheresis days. Forty-five of 58 (78%) patients achieved the minimum CD34+ cells/kg required for transplantation, including 30 (52%) patients who achieved this goal on the first day of apheresis. Overall, 52 (90%) patients proceeded to transplantation, with median neutrophil and platelet engraftment times of 11 and 18 days, respectively. Conclusion: In summary, the alternative 5:00 pm dosing of plerixafor for stem cell mobilization provided a more convenient dosing schedule while ensuring that a majority of lymphoma and myeloma patients achieved the minimum CD34+ cell yield required to proceed to transplantation. Disclosures: Tornatta: Genzyme: Consultancy, Honoraria, Speakers Bureau. Fung:Genzyme: Consultancy, Honoraria, Speakers Bureau.

Peripheral Blood Stem Cell (PBSC) Mobilization in Patients with Multiple Myeloma: Low Dose Versus Intermediate Dose Cyclophosphamide.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2931-2931
Author(s):  
Devendra K. Hiwase ◽  
Anthony P. Schwarer ◽  
Joe J. Mckendrick ◽  
Geraldine M. Bollard ◽  
Smita D. Hiwase ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Low Dose ◽  
Peripheral Blood Stem Cell ◽  
Stem Cell Mobilization ◽  
Number Of Patients ◽  
Cell Mobilization ◽  
Stem Cell Collection ◽  
Intermediate Dose

Abstract Aim: Autologous peripheral blood stem cell transplant (PBSCT) is standard of care for multiple myeloma patients younger than 65 years of age. However there is no agreement on mobilization regimen for PBSC collection. We have compared efficacy and toxicity of low dose & intermediate dose of cyclophosphamide for stem cell mobilization. Methods: Eighty-seven patients with multiple myeloma had stem cell mobilization: Intermediate dose cyclophosphamide (3 to 4 gm/m2) [ID-CY] was used between Jan 1995 to Jun 2002 and low dose cyclophosphamide (1 to 2 gm/m2)[LD-CY] was used between 2002 and 2004. Mobilization chemotherapy: LD-CY or ID-CY was infused along with hydration, antiemetics and mesna. Stem cell collection was planned between day 10 to day 14 after chemotherapy and G-CSF 10 ug/kg (5 to 20 ug/kg) was started 4 days prior to stem cell collection. PBSC collected by processing 7 litres of blood by Fenwal CS3000 (Baxter) or Cobe Spectra. Statistical Analysis: The Mann-Whitney U and Kruskal-Waliis test were used for comparison between treatment groups. Chi-Square and Fisher exact test were used for comparisons of categorical variables Result: There were 87 patients of multiple myeloma, 61 in LD-CY group and 26 in ID-CY group. There was no statistically significant difference between two groups for basic demographic, disease parameters & prior duration of treatment. The median G-CSF/kg dose was similar in both groups. Comparison of Stem cell collection and toxicity: LD-CY Vs ID-CY CD34 Yield LD-CY ID-CY P Number of Patients 61 26 Total CD34/kg Median (Range) 5.17 (0.23 to 17.3) 7.71 (0.08 to 26.4) 0.018 Total CD34/kg/L Median (Range) 0.62 (0 to 2.47) 1.07 (0.01 to 3.77) 0.010 CD34/kg on 1st day of leukapheresis 2.33 (0.03 to 15.8) 5.11 (0.04 to 15.9) 0.001 number of patients collected &gt; 2 x 10^6/kg 54/61 (88%) 24/26(92%) Number of Leukapheresis Median (Range) 2 (1 to 5) 2 (1 to 3) 0.001 Number of patients had febrile neutropenia 8/61(13%) 10/26 (38%) 0.0085 Number of patients required antibiotics 8/61 (13%) 10/26(38%) 0.0085 Number of patients requiring hospitalisation 10/61(16.39%) 11/26 (42.30%) 0.010 Conclusion: There was statistically significant higher stem cell yield with ID-CY as compared to LD-CY, however at the cost of increased toxicity. In LD-CY group 88% patients had &gt;2 x106/kg stem cells collected which is sufficient for single autograft. We conclude that LD-CY mobilisation chemotherapy is adequate for patients who are planned for single autograft with minimal toxicity.

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