DCEP (Dexamethasone, Cyclophosphamide, Etoposide, Cisplatin) Followed by High-Dose G-CSF Is a Highly Efficient and Safe Regimen for Stem Cell Mobilization for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3284-3284
Author(s):  
Jason P. Gonsky ◽  
Nikoletta Lendvai ◽  
Michele L. Donato ◽  
Scott D. Rowley ◽  
Andrew L. Pecora ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Yield ◽  
High Dose ◽  
Outpatient Basis ◽  
Stem Cell Rescue ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Related Mortality

Abstract High dose chemotherapy with autologous stem cell rescue remains a standard therapy for multiple myeloma patients who can tolerate it. A mobilizing regimen for multiple myeloma should ideally allow for a high yield of CD34+ cells, provide anti-myeloma activity, be well tolerated, and have predictable kinetics regarding initiation of collection of stem cells. Higher numbers of infused autologous CD34+ cells allow for more rapid engraftment and lower incidence of transplant-related morbidity and mortality. The goal for patients with myeloma is to harvest enough CD34+ cells to provide at least two autologous transplants. Previous mobilization regimens utilized G-CSF alone or high-dose cyclophosphamide with G-CSF. However, high-dose cyclophosphamide (4–7g/m2) has only modest efficacy against myeloma and is associated with significant morbidity and up to 1–2% treatment-related mortality. DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) is a well established regimen with good efficacy as salvage treatment for myeloma. Additionally, the use of DCEP with G-CSF for mobilization in myeloma has previously been reported to provide an average yield of approximately 6x106 CD34+ cells. We report our experience with DCEP and high-dose G-CSF in mobilizing 88 multiple myeloma patients since 2006. Our regimen consisted of 40 mg dexamethasone IV over 15 minutes x 4 days, cyclophosphamide 500 mg/m2, etoposide 40 mg/m2 (capped at 75 mg), and cisplatin 15 mg/m2 (capped at 25 mg), all continuous IV infusions over 24h x 4 days, with G-CSF starting 24–48h after completion of chemotherapy, administered SQ at 5 mcg/kg x 6 days followed by 10 mcg/kg daily until pheresis is completed. Over 80% of our patients were ready to initiate collection on day 14. Our goal for collection is 10–12x106 CD34+ cells to allow for two or three transplants using at least 4x106 CD34+ cells per transplant. Yields were excellent with a mean yield of 27x106 CD34+ cells, with a range of 7.3–130.5x106 CD34+ cells. 37/88 (42%) of patients required only one day of pheresis, with a mean yield of 34x106 CD34+ cells. 38/88 (43%) of patients required two days of pheresis. Only 15% of patients required more than two days of pheresis. Only 3 patients yielded fewer than 10x106 CD34+ cells (3%), and none yielded fewer than 5x106 CD34+ cells. In conclusion, this regimen is highly efficacious, offers excellent stem cell yields and predictable collection kinetics, can be administered on an outpatient basis, and is safe and well tolerated.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Modified-CVAD Or Modified-Cbad Compared To High Dose Cyclophosphamide For Peripheral Blood Stem Cell Mobilization In Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2036-2036
Author(s):  
Suzanne C Gettys ◽  
Alison M Gulbis ◽  
Kaci Wilhelm ◽  
Yvonne T Dinh ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Febrile Neutropenia ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Time To Progression ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Cell Mobilization

Abstract Background Peripheral blood stem cell (PBSC) mobilization in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (auto-HCT) is commonly carried out using growth factors alone. Approximately 10-15% of patients receive chemomobilization, which assists with cytoreduction and improving the cell yield; however, an optimal regimen has not been established. Here we report our experience with three chemomobilization regimens that have been used at our center: i) cyclophosphamide alone (Cy) ii) modified cyclophosphamide, vincristine, doxorubicin, dexamethasone (mCVAD) and iii) modified cyclophosphamide, bortezomib, doxorubicin, dexamethasone (mCBAD). Methods This is a single-center, retrospective chart review of patients with multiple myeloma undergoing mobilization for an auto-HCT with Cy, mCVAD, or mCBAD between January 1, 2006 and September 30, 2012. A total of 120 patients were identified as initiating stem cell mobilization with Cy (n=39), mCVAD (n=66) or mCBAD (n=15) for multiple myeloma within the defined time period. For the purpose of this study, we combined mCVAD and mCBAD into one group (n=81). The primary objective of this study is to compare successful mobilization and collection (≥ 2 x 106 CD34+ cells/kg collected) between high dose Cy (2-4 g/m2 x1) and mCVAD (cyclophosphamide 350 mg/m2 q12h x 4 days, vincristine 0.4mg continuous infusion daily x 4 days, doxorubicin 10 mg/ m2 continuous infusion daily x 4 days, dexamethasone 40 mg IV daily x 4 days) + mCBAD (same as previous, except using bortezomib 1.3 mg/m2 bolus x 4 days instead of vincristine). Secondary objectives include optimal mobilization (≥ 4 x 106 CD34+ cells/kg), median number of leukapheresis sessions required, use of plerixafor, post-transplant time to neutrophil engraftment, disease status at day 100, time to progression, and incidence of febrile neutropenia, hospitalization, and ICU admissions with each mobilization regimen. Results The groups were well-matched with regard to demographic characteristics. [Table] All 120 achieved a successful mobilization (≥ 2 x 106 CD34+ cells/kg collected) and 118 achieved an optimal mobilization (≥ 4 x 106 CD34+ cells/kg collected). There was no significant difference in the number of leukapheresis sessions (median 2, range 1-7) or plerixafor use (20.5% Cy vs. 8.6% mCVAD or mCBAD, p=0.08). There was no significant difference in the incidence of febrile neutropenia (10.3% Cy vs. 12.4% mCVAD or mCBAD, p=1.00), hospital admissions (18% Cy vs. 21% mCVAD or mCBAD, p=0.81), or ICU admissions (0% Cy vs. 1.2% mCVAD or mCBAD, p=1.00) between the groups. All 14 patients who had an episode of febrile neutropenia were hospitalized. One patient in the mCVAD or mCBAD group was admitted to the ICU with sepsis and renal failure, but was eventually discharged. There were no mobilization-related deaths in either study group. There was no significant difference in the time to neutrophil engraftment for the two groups (median 11 days, range 9-13). The median time to progression was 11.8 months in the Cy group and 9.1 months in the mCVAD or mCBAD group. Conclusion Cy, mCVAD or mCBAD can be used for successful PBSC mobilization in patients with multiple myeloma undergoing an auto-HCT without any unexpected toxicity. These approaches may be further evaluated in a randomized, prospective trial. Disclosures: Off Label Use: Cyclophosphamide, mCVAD, and mCBAD will be discussed as mobilization regimens used for patients with multiple myeloma. Vincristine and doxorubicin do not have specific indications for use in multiple myeloma. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees.

Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2234-2239 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Giovanni Martinelli ◽  
Elena Zamagni ◽  
Maria Rosa Motta ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Preparative Regimen ◽  
Total Body ◽  
High Dose Melphalan

Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P = .04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P = .03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low β2 microglobulin (β2-M) level at diagnosis and TX2, whereas overall survival was correlated with β2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.

Autologous transplantation of granulocyte colony-stimulating factor–primed bone marrow is effective in supporting myeloablative chemotherapy in patients with hematologic malignancies and poor peripheral blood stem cell mobilization

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Antonio de Vivo ◽  
Daniela Damiani ◽  
Alessandro Isidori ◽  
Monica Tani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
High Dose Chemotherapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Myeloablative Chemotherapy ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stimulating Factor

AbstractWe assessed the hematopoietic recovery and transplantation-related mortality (TRM) of patients who had failed peripheral blood stem cell mobilization and subsequently received high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF)–primed bone marrow (BM). Studied were 86 heavily pretreated consecutive patients with acute leukemia (n = 21), refractory/relapsed non-Hodgkin lymphoma (n = 41) and Hodgkin disease (n = 17), and multiple myeloma (n = 7). There were 78 patients who showed insufficient mobilization of CD34+ cells (< 10 cells/μL), whereas 8 patients collected less than 1 × 106 CD34+ cells/kg. BM was primed in vivo for 3 days with 15 to 16 μg/kg of subcutaneous G-CSF. Median numbers of nucleated cells, colony-forming unit cells (CFU-Cs), and CD34+ cells per kilogram harvested were 3.5 × 108, 3.72 × 104, and 0.82 × 106, respectively. Following myeloablative chemotherapy, median times to achieve a granulocyte count higher than 0.5 × 109/L and an unsupported platelet count higher than 20 and 50 × 109/L were 13 (range, 8-24), 15 (range, 12-75), and 22 (range, 12-180) days, respectively, for lymphoma/myeloma patients and 23 (range, 13-53), 52 (range, 40-120), and 90 (range, 46-207) days, respectively, for leukemia patients. Median times to hospital discharge after transplantation were 17 (range, 12-40) and 27 (range, 14-39) days for lymphoma/myeloma and acute leukemia patients, respectively. TRM was 4.6%, whereas 15 patients died of disease. G-CSF–primed BM induces effective multilineage hematopoietic recovery after high-dose chemotherapy and can be safely used in patients with poor stem cell mobilization.

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.

Utilization and outcomes of high-dose chemotherapy and stem-cell rescue in patient with testicular cancer from 2005 to 2014 in United States.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18246-e18246
Author(s):  
Aakash Desai ◽  
Devashish Desai ◽  
Pushti Khandwala ◽  
Smith Giri ◽  
Leonard Joseph Appleman ◽  
...  
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Testicular Cancer ◽  
High Dose Chemotherapy ◽  
Matched Pair ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Stem Cell Rescue ◽  
Matched Pair Analysis

e18246 Background: Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue. This regimen is commonly used as salvage therapy, third-line or later therapy in patients with platinum-refractory disease. The utilization and real-world outcomes and complications of patients with testicular cancer undergoing autologous hematopoietic stem cell transplant (aHSCT) in United States are unknown. Methods: We queried National Inpatient Sample, a large inpatient data set in the United States, from 2005 to 2014 for male patients with testicular cancer or multiple myeloma (control group) receiving aHSCT and compared outcomes between these groups. The primary outcome was in-hospital mortality rate, and the secondary outcomes included in-hospital complications of aHSCT, length of stay and total charges. Outcomes were assessed by means of univariate analysis, multivariate regression and propensity score matched-pair analysis. Results: A total of 391 patients (weighted N = 1,909) with testicular cancer and 4,809 male patients (weighted N = 23,501) with multiple myeloma who underwent aHSCT from 2005 to 2014 were identified. Mean age of patients with testicular cancer was 32.3 years vs 59 years for multiple myeloma patients (p < 0.001) There were no differences in in-hospital mortality rates (1.5% vs 1.4%, p = 0.85) or rates of intubation (2.3% vs 1.6%, p = 0.36), sepsis (7.7% vs 7.5%, p = 0.94), bacteremia (13.5% vs 15.6%, p = 0.42), or stomatitis (43.8% vs 38.8%, p = 0.87) between patients with testicular cancer and multiple myeloma receiving autologous HSCT. However, utilization of total parenteral nutrition was higher in patients with testicular cancer (12.9% vs 4.7%, p < 0.001). There was no difference in length of stay (17.5 vs 17.5 days, p = 0.77) and total charges (121,120$ vs 123,729$, p = 0.74) between two groups. The results were consistent in multivariate and propensity score matched-pair analysis. Conclusions: The in-hospital outcomes of patients with testicular cancer receiving aHSCT appears to be similar to patients with multiple myeloma. However, overall utilization of aHSCT for testicular cancer appears to be low in United States.

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.

Higher Stem Cell Dose Infusion As Rescue After Intensive Chemotherapy Does Not Improve Symptom Burden In Older Patients With Multiple Myeloma and Amyloidosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2161-2161
Author(s):  
Nina Shah ◽  
Loretta A Williams ◽  
Audrey Worthing ◽  
Qiuling Shi ◽  
Xin Shelley Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Older Patients ◽  
Standard Dose ◽  
Symptom Burden ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Dose ◽  
Cd34 Cells ◽  
To Receive

Abstract Introduction High dose chemotherapy and autologous stem cell transplantation (ASCT) has become part of the standard of care for patients with multiple myeloma (MM). However, this process is often associated with a high symptom burden, particularly for older patients and those with concurrent amyloidosis. We have previously shown that symptom burden during ASCT reaches a peak at the time of WBC nadir and is associated with elevated serum levels of IL-6. In addition, other studies have suggested a dose-response relationship between CD34+ cells dose and rate of neutrophil recovery during ASCT. We therefore hypothesized that higher doses of CD34+ stem cells would be associated with an improved symptom outcome, not only due to a potentially shorter time to engraftment, but also through cytokine modulation. Methods We conducted a prospective, randomized controlled trial of patients undergoing ASCT for MM (age > 60) or AL amyloidosis. Patients were randomized to receive either a standard (4-6 e6 CD34+ cells/kg) or high (10-15 e6 CD34+ cells/kg) dose of stem cells after high dose melphalan (200 mg /m2). Symptom burden was assessed at baseline and multiple time points throughout the ASCT process via the MD Anderson Symptom Inventory (MDASI), a validated tool for assessing cancer-related symptom burden. Symptoms were scored on a scale of 1-10 with 10 being the most severe. The primary endpoint was to determine if a higher stem cell dose would result in a lower increase in symptom severity at 1 week post-ASCT. The area under the curve (AUC) of top 5 symptoms was calculated for each group using the trapezoidal rule. Results Between March 2008 and May 2013, 79 patients were enrolled, of which 73 patients were evaluable. 14 of these evaluable patients had light-chain amyloidosis (AL). 35 patients (48%) were randomized to receive a standard stem cell dose while 38 (52%) were randomized to the high stem cell dose arm. Patients were well-matched for age, gender, race, and ISS stage between the two groups. Disease responses prior to ASCT were 28.5% PR, 48.5 % VGPR + CR in the standard dose arm and 47.3 % PR, 31.5 % VGPR + CR in the high dose arm. The median CD34+ cell dose per kg was 4.915 e6 in the standard dose arm and 10.12 e6 in the high dose arm. Median time to ANC >500 was 10 days in both the standard dose arm and in the high dose arm. Similarly, median time to platelet engraftment (platelets >20,000) was 10 days in both arms. From pre-ASCT to day 7, the 5 symptoms with the largest increase were lack of appetite, drowsiness, fatigue, muscle weakness and disturbance in sleep. This severity did not differ between the 2 treatment arms (p=0.827). Over the 28 day course of ASCT the 5 symptoms with the greatest cumulative severity were fatigue, lack of appetite, drowsiness, disturbance in sleep and pain. Again, these increases were not different between the 2 treatment arms (p=0.882, Figure 1). AUCs of those top 5 symptoms did not show any significant difference between groups (228.4±191.0 for high cell dose group, 223.0±94.0 for standard cell dose, p=0.826). Conclusion Infusion of higher autologous stem cell dose after high dose chemotherapy does not yield a difference in engraftment time or symptom burden in the first few weeks after ASCT. Further correlative studies are in process to determine if there are any cytokine differences between the two cell dose arms. Disclosures: No relevant conflicts of interest to declare.

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