scholarly journals High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma

2010 ◽  
Vol 46 (3) ◽  
pp. 364-367 ◽  
Author(s):  
H W Auner ◽  
L Mazzarella ◽  
L Cook ◽  
R Szydlo ◽  
F Saltarelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
High Rate ◽  
Oral Cyclophosphamide ◽  
Cell Mobilization

Cytopenia at Diagnosis Impairs Stem Cell Mobilization Among Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5828-5828
Author(s):  
Selami Kocak Toprak ◽  
Atilla Uslu ◽  
Erden Atilla ◽  
Pervin Topcuoglu ◽  
Gunhan Gurman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Risk Score ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Categorical Variables ◽  
Hematological Toxicity ◽  
Cell Mobilization ◽  
The Impact

Abstract Introduction: The GIMEMA group has recently developed a risk score predicting mobilization failure (Musto et al, EHA 2014). The risk score included age, cytopenia at diagnosis, induction therapy and their toxicity. In this study we aimed to evaluate the impact of these factors on peripheral blood stem cell (PBSC) mobilization among patients with multiple myeloma (MM). Patients and methods: 125 newly diagnosed patients with MM (M: 76, F: 49) planned for autologous stem cell transplantation; median age 58 years (range, 30-67) were included in the analysis. This retrospective study examined the impact of age (> 60 years), gender of the patients, cytopenia (Hb<10 gr/dL, absolute neutrophil count < 1x109/L, thrombocyte count < 100x109/L) at diagnosis, and severe hematological toxicity during induction therapy, the type of induction and mobilization methods, the presence of neuropathy, comorbid diseases such as diabetes mellitus, hypertension and renal failure (creatinine > 2 mg/dL), and the use of beta blocker drugs. Patients with CD34+ levels of <20/μL in peripheral blood at maximum stimulation were considered to be Poor Mobilizers. The total amount of PBSC <5x106/kg after a single mobilization procedure was defined as sub-optimal collection. Poor mobilization was observed in only two patients (<2x106/kg). Statistics: Comparison of categorical variables was evaluated by chi-square test or Fisher exact test. Nominal variables were compared with non-parametrical test, Mann-Whitney U or Kruskal Wallis test. P value below as 0.05 was accepted as significance. Results: Optimal mobilization with median two apheresis (1-4) sessions for PBSC was obtained in 85.6% of the patients (n=107). Median CD34+ cells in this group were 8.33x106/kg (5-27x106/kg). The presence of cytopenia at diagnosis was the only significantly detrimental factor on mobilization (90% vs 77.1%, p=0.04). When the patients was scored in four groups as having single or combined variables (age, cytopenia at the diagnosis or during induction therapy), we were not able to develop a risk score. Conclusions: In our experience, 14.4% of the myeloma patients showed suboptimal or poor mobilization. Use of bortezomib, age, presence of neurotoxicity or hematological toxicity at mobilization did not significantly impair mobilization. We were able to confirm only cytopenia at diagnosis, from the four factors reported by Musto et al, as a detrimental factor impairing the stem cell mobilization. Disclosures No relevant conflicts of interest to declare.

Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3325-3325
Author(s):  
Cristina Gasparetto ◽  
Jon P Gockerman ◽  
Louis F Diehl ◽  
Carlos de Castro ◽  
Joseph O Moore ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Gm Csf ◽  
Best Response ◽  
Frontline Therapy ◽  
Cell Mobilization

Abstract High-dose therapy plus autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM) aged ≤65 years. Melphalan–prednisone (MP)-based therapy is the standard for non-ASCT candidates but is not typically used for transplant-eligible patients as prolonged therapy with melphalan can adversely affect stem cell collection. The phase 3 VISTA study demonstrated the superior efficacy of bortezomib plus MP (VMP) versus MP in previously untreated MM patients ineligible for ASCT. In this phase 2 study, we evaluated the efficacy of a shorter course of VMP on a different treatment schedule as induction therapy prior to ASCT or as frontline therapy in non- ASCT candidates. Patients aged ≥18 years with previously untreated MM received up to six 28-day cycles of bortezomib 1.3 mg/m2 IV, days 1, 4, 8, and 11, plus oral melphalan 6 mg/m2 and oral prednisone 60 mg/m2, days 1–7. After 2–6 cycles, ASCT-eligible patients could proceed to stem cell mobilization (G-CSF 10 mg/kg/day ± GM-CSF 250 mg/m2/ day or cyclophosphamide 4 g/m2 + GM-CSF) and conditioning with melphalan 200 mg/ m2 (140 mg/m2 if aged >65 years). Response was assessed every two cycles and post- ASCT by International Uniform Response Criteria. The primary end point was complete response (CR) rate to VMP. A total of 45 patients were enrolled; 27 were male. Median age was 63 years (range 33–75). MM subtype was 67% IgG, 16% IgA, and 9% each κ- and λ- light-chain; 37% of patients had ISS Stage III MM, 22% had ECOG performance status >1, and 70% had ≥40% plasma cells in bone marrow. In total, 20 patients proceeded to ASCT. Median duration of VMP was 4 cycles in both non-ASCT (range 1–6) and ASCT (range 2–6) patients. Response rate (best response) to VMP was 95% (42 of 44 evaluable patients), including 9% stringent CR (sCR), 9% CR (18% ≥CR [95% CI: 7%, 30%]), 27% very good partial response (VGPR), and 50% partial response (PR). Best response was achieved after cycle 2 in 10 patients, cycle 4 in 25 patients, and cycle 6 in 7 patients. All 20 ASCT patients had successful stem cell mobilization; median yield of CD34+ cells/ kg was 5.6 x 106 (range 2.3–12.2 x 106), in a median of 2 collection days. Post-transplant responses were 10% sCR, 20% CR, 55% VGPR, and 5% PR; the remaining 2 patients need further follow-up for response assessment. Response improved post-VMP to post-ASCT in 10 patients (6 PR to VGPR, 2 PR to CR, 2 VGPR to CR). After median follow-up of 14.0 months (range 7.4–47.7) and 14.6 months (range 8.2–42.9) in non-ASCT and ASCT patients, respectively, both median time to progression and progression-free survival were 19.8 months (95% CI: 14.3 months, not estimable [NE]) in non-ASCT patients and 27.9 months (95% CI: 14.6 months, NE) in ASCT patients. A total of 7 patients (5 non- ASCT, 2 ASCT) have died; 1-year survival rate was 82% (95% CI: 59%, 93%) in non- ASCT patients and 95% (95% CI: 69%, 99%) in ASCT patients. Most common grade 3/4 adverse events in all 45 patients during VMP therapy included peripheral neuropathy (24%), thrombocytopenia (20%), neutropenia (18%), and infection (9%). Only 1 patient had deep-vein thrombosis. In conclusion, VMP represents a highly effective therapy for previously untreated MM, with 45% of patients achieving VGPR or better, including 18% sCR/CR. Toxicities were predictable and generally manageable. Short-course VMP therapy did not negatively impact stem cell mobilization, supporting its use as induction therapy prior to ASCT. Very high post-transplant response rates were seen, with 85% of patients achieving ≥VGPR, including 30% sCR/CR. Since achievement of CR/VGPR is associated with improved long-term outcomes in MM, the preliminary outcome data presented here appear promising; however, longer follow-up is required.

Cyclophosphamide Overcomes the Suppressive Effect of LenalidomideTherapy on Stem Cell Collection in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3024-3024
Author(s):  
Tomer Mark ◽  
David Jayabalan ◽  
Roger N. Pearse ◽  
Jessica Stern ◽  
Jessica Furst ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Stem Cell Collection

Abstract Multiple Myeloma (MM) therapy has evolved over recent years to include powerful new therapeutic agents. The goal for most patients with MM, however, still remains high-dose chemotherapy followed by autologous stem cell transplantations as this procedure has been proven to have a therapeutic benefit. Therefore, the selection of an induction therapy must take into consideration the potential impact on the ability to collect enough stem cells for future transplantation. Recent studies have discussed difficulty in collecting stem cells in patients receiving lenalidomide-based induction therapy using filgastrim (G-CSF) in preparation for autologous stem cell transplantation in MM. It also has been recommended that the duration of lenalidomide induction therapy be limited to 4–6 cycles, since longer treatment time can hinder collection yields. We sought to determine if the addition of cyclophosphamide (CTX) to G-CSF as a mobilization regimen could rescue the ability to collect adequate stem cells for at least two autologous stem cell transplants for patients who had induction therapy with the BiRD (Biaxin® [clarithromycin]/Revlimid® [lenalidomide]/dexamethasone) regimen. BiRD therapy is as follows for each 28-day cycle: Clarithromycin 500mg po BID for days 1–28, Lenalidomide 25mg po daily for days 1–21, and Dexamethasone 40mg po weekly on days 1, 8, 15, and 21. All patients had either Stage II or III MM by Salmon-Durie criteria and were treatment naïve. Patients were advised to undergo stem cell collection after either maximum disease response or disease plateau had been achieved. Prior to stem cell mobilization, BiRD therapy was held for a minimum of 14 days. Stem cell collection was performed after either G-CSF alone at a dose 10 mcg/kg/day for 5–10 consecutive days until a total of 10 × 106/kg CD34+ stem cells had been collected or with the addition of cyclophosphamide (CTX) at a dose of 3g/m2 once prior to the initiation of G-CSF therapy. A total of 28 patients underwent stem cell collection. Stem cell mobilization was attempted with G-CSF alone in 9 instances and with CTX+G-CSF in 20 instances (1 patient underwent mobilization with both G-CSF alone and CTX+G-CSF). In comparison to the G-CSF monotherapy, CTX+G-CSF yielded a significantly greater stem cell collection (mean CD34+ cells collected: 3.78 × 106/kg vs. 32.33 × 106/kg, P < 0.0001). Only 33% of patients who attempted stem cell mobilization with G-CSF alone obtained sufficient CD34+ cell yield vs. 100% of the patients mobilized with CTX+G-CSF (P < 0.0001). The extent of BiRD therapy prior to stem cell mobilization ranged from 2–27 cycles. The number of cycles of BiRD did not significantly impact the success rate of stem cell collection (P = 0.14). In conclusion, the patients mobilized with CTX+G-CSF had a higher number of CD34+ cells collected and were all able collect enough stem cells for two autologous transplants. There was no association with the duration of BiRD therapy and successful CD34+ cell collection. We therefore recommend continuing lenalidomide-based induction therapy until desired tumor reduction goal is achieved and using the CTX in addition to G-CSF to ensure successful stem cell harvest prior to autologous transplantation.

Successful Stem Cell Mobilization with High-Dose Cytarabine Plus G-CSF after Lenalidomide Therapy for Multiple Myeloma - a Series of Four Cases

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5831-5831
Author(s):  
Jun Ishiko ◽  
Kazuaki Sato ◽  
Ruri Kato ◽  
Manabu Kawakami ◽  
Masashi Nakagawa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Negative Impact ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Cell Harvesting ◽  
Cd34 Cells ◽  
High Dose Cytarabine ◽  
Cell Mobilization

Abstract Of late years, newly developed agents, such as bortezomib, lenalidomide, thalidomide, are widely used for treatment against multiple myeloma. After induction therapy, candidates for autologous stem cell transplantation are supposed to be followed by stem cell harvesting. There are several reports showing lenalidomide has a negative impact on stem cell mobilization. This opinion tends to let us refrain from using lenalidomide on the myeloma patients who are eligible for transplantation, even lenalidomide is expected promising. We experienced a series of three clinical cases presenting that stem cells were poorly mobilized with cyclophosphamide (CY) plus G-CSF after lenalidomide treatment, but sequential stem cell mobilization was incredibly improved with high-dose cytarabine plus G-CSF. One additional case who was treated with lenalidomide also presented successful stem cell mobilization with high-dose cytarabine plus G-CSF. Here we show all four cases in detail. Case 1: 66 years old male, symptomatic myeloma after smoldering period. After three course of bortezomib induction, the response was insufficient. Sequentially he was treated with lenalidomide (25mg/day, every day for three weeks with one week rest period) and dexamethasone (Dex) (40mg/day, weekly) for two courses, and finally achieved Partial response (PR). First peripheral blood stem cell harvesting was attempted with high-dose CY (2.0 g/m2, day1-2) + lenograstim (5mg/kg daily, on days 7 until leukapheresis), but mobilization was unsuccessful so harvesting was not performed. For subsequent mobilization, high-dose cytarabine was administered at a dose of 2.0 g/m2 twice daily (day1-2) + lenograstim. Second mobilization was markedly improved, and finally 33.0 x 106/kg CD34+ cells were obtained. Case 2: 63 years old male, symptomatic myeloma, IgG type. This patient was treated with bortezomib, CY and Dex but resulted in disease progression. As an alternative therapy, lenalidomide (10mg/day, daily for three weeks with one week rest) and Dex (40mg, weekly) were used for three cycles. The dose of lenalidomide was reduced due to renal dysfunction. PR was obtained, then first harvesting was attempted with high-dose CY + lenograstim, as case 1, and 0.088 x 106/kg of CD34+ cells were collected, which was not sufficient for transplantation. Second mobilization was performed with high-dose cytarabine as case 1, and consequently we could obtain 60.1 x 106/kg of CD34+ cells; the yield was dramatically improved. Case 3: 41 years old female, symptomatic myeloma after one year course of smoldering myeloma. As an induction therapy, bortezomib, CY and Dex were selected, but finally she could not achieved PR after three cycles. We gave up bortezomib-based induction, and then lenalidomide (15-25 mg on day1-21 with 1 week rest) and Dex (40 mg, weekly) were administrated for five courses, followed by PR. As previous two cases, the first peripheral stem cell collection was initiated with high-dose CY + lenograstim, and it was not sufficient (0.059 x 106/kg of CD34+ cells). And the second mobilization with high-dose cytarabine with lenograstim recovered the yield of stem cell up to 6.90 x 106/kg. Case 4: 63 years old male, symptomatic myeloma. He was treated with bortezomib, Dex with/without CY, but this regimen was not very effectual, and CY caused elevation of aminotransferase (CTCAE grade 3). Then lenalidomide (10-15 mg on day 1-21) and Dex (40 mg, weekly) were administrated for four courses, and the patient achieved PR. Due to the adverse effect of liver dysfunction, we could not use high-dose CY for mobilization. For this case, high-dose cytarabine was selected for first mobilization, and it was very successful, 50.2 x 106/kg of CD34+ cells were harvested. The yields of PBSC from all four cases are summarized on Table 1. These four cases suggest mobilization with high-dose cytarabine could be an alternative option for poor mobilizer of myeloma patient treated with lenalidomide-based induction. This fact may enable us to choose lenalidomide, not only bortezomib, for induction even for transplant-eligible cases. Figure 1 Figure 1. Disclosures Ishiko: Celgene: Honoraria.

scholarly journals Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3373-3373 ◽  
Author(s):  
Patrick Wuchter ◽  
Uta Bertsch ◽  
Hans-Juergen Salwender ◽  
Markus Munder ◽  
Mathias Haenel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The German-Speaking Myeloma Multicenter Group (GMMG) has initiated a randomized multicenter phase III trial on the effect of elotuzumab in VRD (bortezomib, lenalidomide, dexamethasone) induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6 trial, NCT02495922). The study compares four cycles induction therapy with VRD vs. VRD + elotuzumab, followed by standard intensification (i.e. mobilization and stem cell transplantation), two cycles consolidation with VRD/VRD + elotuzumab and lenalidomide maintenance +/- elotuzumab. The primary endpoint is determination of the best of four treatment strategies regarding progression-free survival. Here we present a first analysis of stem cell mobilization within this study. Patients and Methods: We performed a retrospective analysis of collection data on all patients who underwent peripheral blood stem cell (PBSC) collection between trial initiation in June 2015 and June 2016. Only patients with completely available datasets in respect of mobilization were considered (n=111). The vast majority of 99 patients (89%) received chemomobilization with CAD (cyclophosphamide, adriamycin, dexamethasone) followed by 5-10 µg G-CSF /kg body weight (bw) /d (starting day +9 until completion of PBSC collection), while in one case (1%) dexamethasone was omitted and in 10 cases (9%) cyclophosphamide mono was administered. One patient underwent steady-state mobilization with G-CSF only (10µg /kg bw /d). 55/111 patients received VRD (50%), whereas the remaining patients received VRD + elotuzumab. According to the recommendations of the study group, PBSCs for three stem cell transplants were to be collected. One transplant ideally consisted of ≥2.5 x10^6 CD34+ cells /kg bw, but in the event of poor mobilization as low as ≥2.0 x10^6 CD34+ cells /kg bw would be considered acceptable. Results: The median number of collected CD34+ cells was 10.4 x10^6 /kg bw (range 2.88 to 23.01 x10^6 /kg bw). Overall, 92 patients (83%) collected ≥7.5 x10^6 CD34+ cells /kg bw and another 12 patients (11%) collected between 6.0 and 7.5 x10^6 CD34+ cells /kg bw, resulting in three transplants, respectively. Only 7 patients (6%) collected below 6.0 x10^6 CD34+ cells /kg bw; 5 of them had been treated in the VRD-arm without elotuzumab. Due to insufficient PBSC mobilization after conventional treatment, 14 patients (13%) received a rescue mobilization with plerixafor, from which 12 patients collected ≥6.0 x10^6 CD34+ cells /kg bw. Overall, 7 serious adverse events (SAEs) occurred during mobilization phase, 4 of them in the study arm with elotuzumab. Conclusions: Cyclophosphamide-based chemomobilization after induction therapy with VRD is feasible. Efficient PBSC collection of ≥6.0 x10^6 CD34+ cells /kg bw could be performed in 104 of 111 patients (94%), with a low incidence of SAEs. The need for rescue mobilization was not higher than that of comparable previous GMMG treatment protocols. The addition of elotuzumab during induction phase did not impede PBSC collection. Disclosures Wuchter: Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bertsch:Janssen: Research Funding; Celgene: Research Funding; Chugai: Research Funding. Munder:Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Fenk:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Hillengass:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Research Funding; Sanofi: Research Funding. Raab:Novartis: Consultancy, Research Funding; BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ho:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Medac: Other: Travel, accomodations or expenses; Baxalta: Honoraria; Amgen: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel, accomodations or expenses; Janssen: Consultancy, Honoraria; Celgene: Other: Travel, accomodations or expenses; BMS: Consultancy, Honoraria. Weisel:Onyx: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldschmidt:Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy

Leukemia ◽  
2011 ◽  
Vol 25 (10) ◽  
pp. 1627-1631 ◽  
Author(s):  
F Cavallo ◽  
S Bringhen ◽  
G Milone ◽  
D Ben-Yehuda ◽  
A Nagler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Newly Diagnosed ◽  
Cell Mobilization

The Combination of Cyclophosphamide and Thalidomide During Induction Therapy for Multiple Myeloma Results in a High Rate of Stem Cell Mobilization Failure.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2147-2147
Author(s):  
Holger W Auner ◽  
Luca Mazzarella ◽  
Lucy Cook ◽  
Richard Szydlo ◽  
Francesca Saltarelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Drug Combinations ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
High Rate ◽  
Control Group ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Abstract 2147 Poster Board II-124 In the era of novel therapeutic agents, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remains an integral component of treatment for multiple myeloma (MM), with a proportion of patients undergoing more than one ASCT during the course of their disease. Therefore, the choice of new drug combinations for induction therapies must take into consideration the requirement to collect a sufficient number of stem cells, which is also reflected in a recently published consensus perspective of the International Myeloma Working Group. The immunomodulatory drug Lenalidomide and the alkylating agent Melphalan have a substantial impact on stem cell mobilization, but the effect of induction therapies containing either Thalidomide or Cyclophosphamide on the stem cell collection yield is negligible. We considered the possibility that the combination of Cyclophosphamide and Thalidomide, which is widely used as an induction regime particularly in the UK as part of the CTD regime (with Dexamethasone), could have an additive impact on the stem cell pool and cause mobilization failures. We carried out a retrospective analysis of the outcome of peripheral blood stem cell mobilizations in MM patients performed at our institution over a four-year period in patients who had received CTD (n=55), and compared them with a control group of patients (n=56) who had received VAD (Vincristine, Doxorubicin, Dexamethasone; n=30) or Z-Dex (Idarubicin, Dexamethasone; n=26) during the same period. There were no differences between the CTD and control group in terms of age, MM subtype, disease stage, or remission status at the time of stem cell mobilization. All mobilizations were performed with Cyclophosphamide (4g/m2) and G-CSF (5-10μg/kg). Apheresis was attempted when the peripheral blood CD34 count was >10 × 103/ml, and the standard harvest target was 4 × 106 CD34+ cells/kg, with a minimal target of 2 × 106 CD34+ cells/kg. The total number of CD34+ cells harvested was substantially lower in the CTD group (5.2 vs. 9.7 × 106/kg, p=0.002), and a higher number of patients in the CTD group underwent more than one apheresis procedure (52.8% vs. 32.1%, p=0.012). The number of CD34+ cells harvested on the first day of apheresis and per apheresis procedure were also lower in the CTD group (2.8 vs. 7.3 × 106/kg, p=0.002; 2.6 vs. 6.7 × 106/kg, p=0.002). More patients in the CTD group failed to achieve both the standard (36.4% vs. 16.1%, p=0.021) and minimal (19.2% vs. 5.4%, p=0.036) stem cell harvest target. The failure rate on the first day of apheresis was also higher in the CTD group both for the standard (56.3% vs. 28.6%, p=0.003) and the minimal target (36.7% vs. 16.1%, p=0.041). There was no difference in stem cell yield between the VAD and Z-Dex groups. Age and number of induction chemotherapy cycles did not have an impact on mobilization failure in the entire cohort or the CTD group alone. In the CTD group, 18% of patients underwent re-mobilization with Etoposide (1.6g/ m2) and G-CSF (n=8), or with Plerixafor (240μg/kg) and G-CSF (n=2), which was successful in all patients. These results demonstrate that the CTD induction regime results in a high rate of stem cell mobilization failures, which is associated with the requirement for an increased number of apheresis and re-mobilization procedures. The observations provide novel evidence that drugs with no previously demonstrated significant effect on stem cell mobilization can have a considerable negative impact on the stem cell yield when used in combination. The possible benefit of new drug combinations has to be balanced against the increase in cost, the potentially higher rate of complications, and delays or failures to progress to ASCT resulting from impaired stem cell mobilization. Disclosures: No relevant conflicts of interest to declare.

The effect of induction therapy with novel agents on stem cell mobilization in multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8102-8102 ◽  
Author(s):  
A. Mazumder ◽  
S. Jagannath ◽  
D. Vesole
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Stem Cell Markers ◽  
Number Of Patients ◽  
Cd34 Cells ◽  
Cell Mobilization

8102 Background: Thalidomide or bortezomib combined with dexamethasone (TD or BD respectively) are now being increasingly used as induction regimens for newly diagnosed multiple myeloma. There are conflicting reports on the effects of T on stem cell mobilization. Since we have used both these regimens at our center, we performed a retrospective analysis of stem cell mobilization after induction therapy with either TD (n = 22) or BD (n = 18). Methods: The patients were balanced with respect to initial Durie-Salmon stage, median number of cycles of induction therapy prior to collection, response to induction therapy, bone marrow cellularity and involvement, and time from end of therapy to collection. All patients were mobilized with G-CSF 10mcg/kg and collected in a large volume pheresis, with a goal of at least 6x10(6) CD34+ cells/kg (for tandem transplant). Results: To achieve our stem cell goal, the number of patients who required 3 or more phereses in the TD group was 17/22 whereas it was only 4/18 in the BD group. (p<0.005). 3/3 patients who had received lenalidomide also required 3 or more phereses. Also, the number of CD34+ cells/kg obtained in the TD group was less–mean of 2.8x10(6) per pheresis, as compared to a mean of 5.2x10(6) per pheresis in the BD group (p<0.01). Time to neutrophil engraftment was similar in both groups. However in the TD group there was a 1 day delay in platelets > 20,000/ul (p<0.05). Conclusions: Thus, thalidomide induction led to a lower yield of stem cells when compared to bortezomib. Differences in stem cell markers are being investigated. This may become especially important when limiting numbers of stem cells are available from elderly patients, those with prior radiation or bulk disease and when used for in vitro manipulation. It is possible that agents such as bortezomib may alter the bone marrow microenviroment differently from imids such as thalidomide. No significant financial relationships to disclose.

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