Autologous Stem Cell Transplant in Patients with Multiple Myeloma Previously Treated with Lenalidomide: A Single-Institution Experience Using An Intermediate-Dose Cyclophosphamide-Based Regimen

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4391-4391
Author(s):  
Asif Alavi ◽  
Rada Grubovic ◽  
Gary J. Schiller
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treated Group ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Peripheral Stem Cells

Abstract Abstract 4391 Background: High dose chemotherapy followed by autologous transplantation of peripheral blood stem cells plays an important role in the management of intermediate- and advanced-stage multiple myeloma. In order for successful engraftment to occur, adequate numbers of high quality peripheral stem cells must be harvested prior to transplantation. Mobilization of PBSC in patients treated with lenalidomide has been associated with poor apheresis collections after G-CSF mobilization. The purpose of this study is to present our institution’s experience utilizing an intermediate-dose cyclophosphamide-based mobilization regimen. Methods: We retrospectively analyzed data for patients with multiple myeloma who underwent autologous stem cell transplant at UCLA between 2006 and 2010. Data were obtained from the database of the UCLA Heme Malignancy/Stem Cell Transplant Unit, the electronic health record system and stem cell processing laboratory. All patients underwent mobilization with a regimen of cyclophosphamide 2.5g/m2 IVPB, G-CSF 10 mcg/kg/day for 4 days SQ, and prednisone 2mg/kg/day for 4 days po. The number of CD 34+ cells was used as a marker for the number of peripheral stem cells collected. Minimum dose collected to ensure adequate engraftment was 2×106/kg CD34+ cells. Patients were conditioned with melphalan 100mg/m2/d x2 (unless there was evidence of renal failure, in which case the dose was reduced to 100mg/m2) with subsequent infusion of stem cells. Neutrophil engraftment was defined as the first day of absolute neutrophil count greater than 500×106/L ≥ 7 days after transplant. Results: Autologous stem cell transplant was performed in 103 patients with multiple myeloma at UCLA between 2006 and 2010. Median number of apheresis procedures was 1 (1–12) with a median of 4.4×106/kg (1.4–33.5) CD34+ cells collected. Median time to engraftment was 10 (8–18) days. Thirty-five patients received lenalidomide at some point in their pretransplant treatment. Median number of apheresis procedures was 1 in both lenalidomide and non lenalidomide treated groups. In the lenalidomide treated group 54% required only one collection versus 75% in the non lenalidomide treated group (p=0.033). In the lenalidomide treated group 31% required 3 more or more collections versus 10% in non lenalidomide treated group (p=0.0075). Three patients in the lenalidomide group had subsequent mobilization with plerixafor with one of these requiring bone marrow harvesting. Median CD34+ cells collected was 3.5×106/kg and 4.9×106/kg (p=0.246) in the lenalidomide and non-lenalidomide groups respectively. Both groups had a median time to neutrophil engraftment of 10 days with a similar range. Conclusion: Pre-transplant use of lenalidomide adversely affected the number of stem cell apheresis procedures required to procure adequate stem cell dose as evidenced by a greater percentage requiring 3 or more collections. However, despite prior lenalidomide exposure, the use of our mobilization regimen permitted adequate collection, with the majority of patients requiring only one apheresis procedure, and led to an equivalent time to neutrophil recovery. Disclosures: Off Label Use: Cyclophosphamide and G-CSF for mobilization of stem cells.

Effect of lenalidomide induction therapy on peripheral blood stem cell collection in patients undergoing autologous stem cell transplant for multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6549-6549
Author(s):  
Divaya Bhutani ◽  
Jeffrey A. Zonder ◽  
Judith Abrams ◽  
Voravit Ratanatharathorn ◽  
Joseph P. Uberti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Number Of Cycles ◽  
Stem Cell Collection

6549 Background: Autologous stem cell transplant (ASCT) remains part of standard therapy for Multiple Myeloma (MM). Lenalidomide (LEN) is a newer, effective therapy for MM. It has been suggested that prior LEN therapy is associated with an increased risk of stem cell collection failure, particularly when only G-CSF is used for mobilization. Methods: We conducted a retrospective chart review of 310 consecutive MM pts who underwent pheresis to collect stem cells for first ASCT between July 1, 2007 and June 30, 2011 at the Karmanos Cancer Institute. We compared differences in quantity of CD34 cells collected, days needed to collect the target number of cells (> 2.5 x 10*6 CD34+ cells/kg), days to platelet and neutrophil engraftment. We also evaluated the association between CD34+ cells collected and the number of cycles of LEN therapy. Results: Of 310 patients, 90% were mobilized with only G-CSF initially. Patients were analyzed as two groups: LEN exposed (LEN(+); n = 128) and LEN naive(LEN(-); n = 182). Median age in both groups was 58 years. No differences in race, sex and MM stage distribution were observed between the two groups. The median number of stem cells collected in the LEN(+) group was significantly less than the LEN(-) group (6.46 vs. 7.56 x 10*6 CD34 cells/kg; p= 0.0004). In addition, the median number of pheresis sessions required for adequate stem cell collection were significantly more in the LEN(+)group as compared to LEN(-) group (2 vs.1 sessions; p=0.002). In the LEN(+) group, there was a negative correlation between CD34+ cells collected and the prior number of cycles of LEN (p=0.0001). There was no statistically significant excess in the number of stem cell collection failures with G-CSF in the LEN(+) group (7% vs. 4% p=0.31). All pts who failed collection after G-CSF were successfully collected with Cytoxan or Plerixafor priming. LEN exposure had no effect on post-ASCT neutrophil or platelet recovery. Conclusions: Although Lenalidomide exposure is associated with a slightly lower CD34+ stem cell yield and on average an extra session of pheresis when G-CSF is used for mobilization, collection failure is uncommon and post-ASCT engraftment is normal.

Weekly Cyclophosphamide and Alternate Day Prednisone: An Effective, Convenient and Well Tolerated Treatment for Relapsed Multiple Myeloma Following Autologous Stem Cell Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4917-4917
Author(s):  
A. Keith Stewart ◽  
Young Trieu ◽  
Suzanne Trudel ◽  
Greg Pond ◽  
Joseph Mikhael ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Alkylating Agents ◽  
Progression Free Survival ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Protein Reduction

Abstract Alkylating agents remain among the most potent therapies available for treatment of Multiple Myeloma (MM). Their use prior to, or following, autologous stem cell transplant (ASCT) is, however, compromised by concerns about stem cell quality and by myelosuppression limiting effective dose delivered. To address this concern we have studied a combination of cyclophosphamide 500 mg p.o. once weekly and prednisone 100 mg p.o. on alternate days in 66 patients requiring salvage therapy post-ASCT. Dose reductions were allowed for toxicity beginning at cycle 2. On an intent to treat basis, 66 patients received this regimen, however, 7 of these patients were not fully evaluable for response due to non-secretory disease. Of the 59 patients evaluable for response, the median time from transplant to treatment was 26.4 months (range, 6.0 to 66.6). The median time from post-transplant relapse to start of cyclophosphamide and prednisone (C/P) therapy was 1.4 months. The median number of therapies from time of diagnosis to C/P initiation was 2 (range, 1.0 to 5.0). At the date of analysis, treatment with C/P is ongoing in 12 (20.3%) patients, with a median duration of 3.6 months (range, 1.9 to 11.6). The 47 patients who have completed C/P therapy were treated for a median time of 5.5 months (range, 0.5 to 21.7). The reason for discontinuation among these 47 patients included disease progression (42.6% of patients discontinued), plateau disease (21.3%), receiving a second transplant (17.0%), toxicity (10.6%), or switched to another regimen (8.5%). A partial response (>50% protein reduction) was obtained in 37.3% of patients, 18.6% attained minimal response (25–50% protein reduction), 33.8% patients stable disease, while 10.2% patients had progressed on treatment. The estimated median (95% CI) months of progression-free survival after start of C/P treatment is 14.9 (8.7, 21.7). Twenty-three (38.9%) of patients have relapsed after C/P treatment, a median (range) of 8.7 (0.5–65.7) months after start of C/P treatment. At 6 months 74.3% (95% C.I. 61.9% – 89.1%) of patients were progression-free with 28% (95% CI: 16.1–49.2%) progression free at two years. At time of analysis, 44 (74.6%) patients are still alive, with a median follow up of 10.6 months (range, 1.2 to 65.7) since the start of C/P therapy. Fifteen patients have died at a median 13.0 months (range, 1.4 to 61.7) since the time of C/P initiation. The median overall survival (95% C.I.) is estimated to be 35.9 months (24.2, NA). These results demonstrate that the combination of oral cyclophosphamide and prednisone is an effective (56% MR or PR), very well tolerated (10% discontinued due to toxicity) and convenient treatment as salvage MM therapy post-ASCT. The relative lack of myelosuppression allows for re-collection of stem cells and salvage transplant while retaining other active second line agents for later relapse. This regimen thus compares favorably with recent salvage therapeutics introduced in MM and is now being studied in combination with these newer active agents and in induction therapy.

Stem Cell Transplant without Growth Factor In Multiple Myeloma: Engraftment Kinetics, Bacteremia, and Hospitalization.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3469-3469
Author(s):  
Morie Abraham Gertz ◽  
Dennis Gastineau ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
The United States ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Abstract 3469 Introduction: Stem cell transplantation is important in the management of multiple myeloma. In the United States, the standard of care is administration of growth factors to accelerate neutrophil recovery after stem cell transplant. The need for growth factors after transplant has not been investigated recently. Patients: We analyzed a cohort of 166 patients at our institution who underwent autologous transplant for multiple myeloma without receiving growth factors after transplant and compared them with 498 patients who received standard filgrastim beginning on posttransplant day 5. TABLE Results: A neutrophil count of 500/μL was achieved in a median of 12.5 days in patients receiving growth factor, compared with 13.5 days in those not receiving growth factor (P<.001) Fig 1. Platelet engraftment was identical (median, 14.5 days; P=.12) in both groups, despite a lower median number of CD34+ cells infused in patients who did not receive growth factors. Incidence of nonstaphylococcal bacteremia was identical in both groups. The median hospital stay was 3.5 days shorter in the group not receiving growth factor. Bacteremia impacted platelet but not neutrophil engraftment. Figure 2 Conclusion: It is feasible and reasonable to perform autologous stem cell transplant for multiple myeloma without administering growth factors. Estimated savings would be $4,600 for each transplanted patient. Growth factor administration is not required for a safe outcome and decreases the number and severity of some of the fluid-related complications after transplant such as acute respiratory distress syndrome, allergic reactions, alveolar hemorrhage, and rarely splenic rupture. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lacy:Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

scholarly journals Mobilization potential of patients with lymphomas and multiple myeloma involved in autologous stem cell transplant

2020 ◽  
Vol 71 (4) ◽  
pp. 54-62
Author(s):  
Katarina Stančev ◽  
Milena Todorović-Balint
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Therapeutic Response ◽  
Stem Cell Transplant ◽  
Clinical Stage ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Mobilization Potential ◽  
Cd34 Cells ◽  
Hodgkin's Lymphomas

Introduction: High-dose chemotherapy by following autologous stem cell transplant (ASCT) is a standard treatment of multiple myeloma (MM), relapse of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphomas (NHL). Monitoring of clinical and biochemical characteristics, as well as post-transplant parameters, all point to the importance of mobilization potential. Aim: To evaluate the association of early recovery of neutrophil granulocytes ≥0.5 x 109 /L after 11 days of transplantation (ANC500_11), platelets ≥20 x 109 /L after 13 days of transplantation (PLT20_13) with gender, age, duration of mobilization, as well as radiotherapy or chemotherapy, dose CD34+ cells in the apheresis product and therapeutic response. Material and Methods: The retrospective study included 100 patients, out of which 51 patients with MM, 27 with NHL and 22 with HL, in the period from November 2015, ending December 2018. Results: The median age of the patient was 53(20-67) years. According to the DSS, 69% were in IIIA, while 12.5% of patients were in the IIIB clinical stage. According to the Ann-Arbor staging 92% patients were in the II or III clinical stage. The mediana number of CD34+ cells in the apheresis product was 6.7×106 /kgBM. The median in all three mobilization attempts was 6 days. Engraftment is most often detected during the 11th day. In 78% of patients, mobilization was successful in the first attempt (≥2.0x106 /kgBM) among which 86% were MM and 69,4% of lymphomas (p<0.05). The impacts of age, the number of CD34+ cells in the peripheral blood and the duration of the mobilization did not show a significant difference (p>0.05) in relation to the recovery of ANC500_11 and PLT20_13. Conclusion: Satisfactory CD34+ cellular yield can be provided in the first mobilization attempt in most of the patients using of GCS-F, while in the further mobilization attempts plerixafor was necessery. As opposed to gender, age, duration of mobilization and therapeutic response have no impact on ANC500_11 and PLT20_13.

Fractionated Stem Cell Infusions for Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4550-4550
Author(s):  
Kevin Wood ◽  
Sergio A Giralt ◽  
Guenther Koehne ◽  
David Chung ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Study Group ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Engraftment Syndrome ◽  
High Dose Melphalan

Abstract Abstract 4550 Background: High dose therapy with autologous stem cell transplant (SCT) is an established therapeutic modality for multiple myeloma (MM). Although effective, it is associated with significant symptom burden due to the obligate period of neutropenia in addition to an increased risk of infectious complications. In animal models, infusing stem cells over a period of days enhances immune reconstitution (Felfly H, et al. Br J Haematol. 2009; 148: 646–658). We hypothesized that multiple stem cell infusions could reduce the period of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Methods: We are conducting a phase II trial of multiple fractionated autologous stem cell infusions after high-dose Melphalan. We compared initial engraftment kinetics of the first 14 patients to receive multiple infusions (Days 0, +2, +4, +6) after high-dose Melphalan (study group) to 23 patients receiving high-dose Melphalan followed by the standard single stem cell infusion (Day 0) (standard group). Pegfilgrastim was given to all patients on Day +1. All patients underwent SCT between October 2011 and July 2012. Results: Results are shown in Table 1. Similar numbers of stem cells were collected in the study and standard groups. The total number of stem cells infused was 9.7 × 10∧6 CD34+ cells/kg in the study patients compared to 5.0 × 10∧6 CD34+ cells/kg in the standard patients. To date, the median duration of neutropenia (days of ANC < 500) and lymphopenia (days of ALC < 500) as well as the days to neutrophil, lymphocyte and platelet engraftment are similar. There are no significant differences in the number of red cell or platelet transfusions, days of fever, diarrhea, empiric antibiotics or documented infections. Despite receiving multiple infusions, none of the patients in the study group experienced an infusion reaction. Engraftment syndrome occurred in 3/14 (21%) of the study patients. The median duration of hospitalization was 15 days in the study cohort versus 17 days in the concurrent control group (P = 0.01). Conclusion: Multiple stem cell infusions following high dose Melphalan in patients with MM were not associated with a higher incidence of adverse side effects from DMSO nor unexpected frequency of engraftment syndrome. Fractionating stem cells over a period of days may result in less antibiotic use, reduced frequency of infection and was associated with shorter hospitalizations. We continue to collect patient reported symptom scores in order to determine if we can improve patient experience during SCT. Disclosures: No relevant conflicts of interest to declare.

Outcomes of G-CSF alone vs G-CSF with upfront plerixafor vs G-CSF/chemotherapy for collection of autologous stem cells in patients with multiple myeloma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19504-e19504
Author(s):  
Giampaolo Talamo ◽  
Melissa George ◽  
W. Christopher Ehmann ◽  
Joseph J. Drabick ◽  
Shin Mineishi
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Peripheral Blood Stem Cells ◽  
Group A ◽  
Group B

e19504 Background: Strategies for optimizing the collection of peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) vary among transplant centers, and include the use of G-CSF alone or in combination with plerixafor, or mobilization chemotherapy + G-CSF. In 2010, we started using “upfront” plerixafor, given on the day before the PBSC collection. Methods:We retrospectively analyzed the outcomes of 423 consecutive MM patients who underwent PBSC collections at the Penn State Hershey Cancer Institute. PBSC were collected after mobilization chemotherapy + G-CSF 5 mcg/Kg/day (group A, 91 pts), G-CSF alone, 10-16 mcg/Kg/day (group B, 72 pts), and G-CSF with “upfront” plerixafor 0.16-0.24 mg/Kg on the day before the stem cell collection (group C, 245 pts). Fifteen patients were excluded from the analysis because they collected with chemotherapy + plerixafor, received pegylated G-CSF, or plerixafor “on demand”, i.e., after failure to achieve an adequate number of stem cells on the first day of collection. We compared yields, number of days required for apheresis, clinical outcomes, and adverse events among these groups. Results: The median number of PBSC collected was 16.4 (range, 0.1-134), 4.2 (range, 0-12), and 6.2 (range, 0.2-41.2) million CD34+ cells/Kg in group A, B, and C, respectively (p<0.001). The mean number of days to collect PBSC was 1.5, 1.5, and 1.3 in group A, B, and C, respectively (p=0.033). Collection failure, defined as a yield <2 million CD34+cells/Kg, was observed in 5 (5.5%), 9 (12.5%), and 15 (6.1%) patients of group A, B, and C, respectively (p<0.001). Twenty patients in group A developed neutropenic fever requiring hospital admission, and 1 of them died of septic shock, whereas no mortality was observed in groups B or C. No difference in the rapidity of PBSC engraftment, progression-free survival, and overall survival was observed among the 3 groups. Conclusions:In patients with MM, the upfront use of plerixafor with G-CSF provided the best collection strategy: it avoided the morbidity and mortality associated with the mobilization chemotherapy, and it provided higher yields than G-CSF alone.

scholarly journals Patient‐reported outcomes following autologous stem cell transplant for patients with multiple myeloma

eJHaem ◽  
2021 ◽  
Author(s):  
Noa Biran ◽  
Wanting Zhai ◽  
Roxanne E. Jensen ◽  
Jeanne Mandelblatt ◽  
Susan Kumka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Patient Reported Outcomes ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Patient Reported
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