Intermediate-dose Cyclophosphamide Research Articles

Intermediate-dose cyclophosphamide and bortezomib for PBSC mobilization in multiple myeloma

Although the incorporation of bortezomib into induction regimens has improved response rates in patients with multiple myeloma (MM), the role of bortezomib in the peripheral blood stem cell (PBSC) mobilization remains unclear. We assessed the PBSC mobilization efficacy, safety, and disease response of intermediate-dose cyclophosphamide and bortezomib in the PBSC mobilization. Twenty-one patients with newly diagnosed MM were enrolled in a phase II, non-randomized study that used bortezomib (1.3 mg/m2/day on days 1, 4, 8, and 11) and intermediate-dose cyclophosphamide (2 g/m2/day on days 2, 3) (Bor-ID-CY). The data from 15 patients who received intermediate-dose cyclophosphamide (ID-CY) were used as a historical control group. The total CD34 + cell yield of Bor-ID-CY and ID-CY groups were not significantly different (median 6.3 ×106/kg vs. 6.5 ×106/kg, p = 0.26). All three patients with mobilization failure of two groups had t(11;14). Six patients in Bor-ID-CY group were upgraded from a status that was less than a very good partial response (VGPR) at the time of PBSC mobilization to a VGPR or better after PBSC mobilization (p = 0.014). Four patients in Bor-ID-CY group developed sepsis. The time to engraftment was similar in the two groups. The addition of bortezomib to ID-CY did not impact the stem cell yield or quality.

Higher efficacy of oral etoposide for mobilization of peripheral blood stem cells in patients with multiple myeloma

This study compares the efficacy, toxicity, hematopoietic recovery, and cost of stem-cell mobilization using intermediate-dose cyclophosphamide (IDCy) plus granulocyte colony-stimulating factor (G-CSF) compared with etoposide (VP-16) plus pegylated granulocyte colony-stimulating factor (PEG-rhG-CSF) in multiple myeloma (MM) patients. Two hundred forty-four consecutive patients undergoing mobilization with IDCy (3-3.5 g/m2) plus G-CSF (n = 155) were compared with patients receiving VP-16 plus PEG-rhG-CSF (n = 89), including oral etoposide (n = 65) and intravenous etoposide (n = 24). Compared with IDCy, VP-16 use was associated with significantly higher median peak peripheral blood CD34 + cell count (8.20 [range: 1.84-84] × 106/kg vs 4.58 [range: 0.1-27.9] × 106/kg, P= .000), and ideal CD34 + cell yield of more than 6 × 106/kg (56.8% vs 35.1%, P= .001), notably with a higher efficacy in oral VP-16 use compared with IDCy use (CD 34 + cell counts: median peak peripheral blood 5.87 vs 4.58 × 106/kg and ≥6 × 106/kg [48.4% vs 35.1%]). The median number of apheresis courses was reduced from two in the IDCy group to one in the VP-16 group (P = .000). IDCy use was associated with significantly more frequent episodes of neutropenia (70.2% vs 35.2%; P= .000), intravenous antibiotic use (13.2% vs 11.4%; P= .672), and hospitalization (P = .000). The recoveries of neutrophils and platelets after autologous stem-cell transplantation were significantly faster in the VP-16 group compared with the IDCy group (P = .000). Our data indicate robust stem-cell mobilization in MM patients with VP-16 delivered either orally or intravenously. When compared with intravenous VP-16, oral VP-16 mobilization was associated with significantly more convenient, lower average total costs, and especially decreased the risk of hospital visits and exposure.

Safety of outpatient stem cell mobilization with low- or intermediate-dose cyclophosphamide in newly diagnosed multiple myeloma patients.

Autologous stem cell transplantation is the gold standard for eligible newly diagnosed multiple myeloma patients. Patients are usually hospitalized for administration of mobilization chemotherapy. We aimed to assess safety and efficacy of mobilization therapy with low-dose (2g/m2 ) and intermediate-dose (3-4g/m2 ) cyclophosphamide administered as outpatient. A total of 176 consecutive newly diagnosed transplant-eligible myeloma patients receiving outpatient mobilization were retrospectively evaluated. Induction therapy was mainly performed with new drugs (91%). Chemotherapy was very well tolerated with 16.6% of patients having all-grade adverse events (AEs) and only 1.2% having severe AEs. The most frequently reported AEs were nausea and vomiting grade 1-2 (6.8%). Only 5.7% of patients required hospitalization for AEs. Stem cell collection was successful in 93.1% of patients, with a median CD34+ harvest of 8.7×106 /kg. Target for 2 autologous stem cell transplantation (at least 6 CD34+ ×106 /kg) was reached by 76.3% of patients. Administration of plerixafor on demand was necessary in 12.1% of patients. Outpatient mobilization with low- and intermediate-dose cyclophosphamide appears an efficient and safe procedure, with minimal and manageable AEs and low rate of hospitalization.

Outpatient Stem Cell Mobilization with Low and Intermediate Dose Cyclophosphamide Is a Safe and Effective Procedure in Newly Diagnosed Multiple Myeloma Patients Eligible for Stem Cell Transplantation

▪BackgroundEven in the era of new drugs and despite the use of very effective combination regimens, autologous stem cell transplantation (ASCT) remains the gold standard treatment for eligible newly diagnosed multiple myeloma (NDMM) patients (pts) (Attal, NEJM 2017). Pts are usually hospitalized for administration of mobilization chemotherapy (cht) and Cyclophosphamide (CY) at different doses is the most used regimen for collecting peripheral blood stem cells in MM. Clinical trials demonstrated that low (1.5-2 g/m2, LD-CY) and intermediate dose CY (3-4 g/m2, ID-CY) combined with G-CSF are efficient mobilizing regimens with less toxicity compared with high dose CY (7 g/m2, HD-CY) (Fitoussi BMT 2001, Jantunen BMT 2003). On the other hand, hospitalization increases costs and pts discomfort.ObjectiveTo evaluate the safety of mobilization therapy with LD- and ID-CY administered as outpatientMethodsWe retrospectively reviewed all consecutive patients (n=176) with NDMM undergoing outpatient stem cell mobilization in two centers between 2002 and 2017 with CY 2 (40.3%) or 3-4 g/m2 (59.7%) + G-CSF after induction therapy. Pts characteristics, induction regimens and responses are described in Table 1. Day 0 was defined as the CY infusion day. CY was administered in 2-4 consecutive 1h infusions (depending on total dose). Hyper-hydration, antiemetics and the uroprotectant uromitexan begun IV 1 hour before CY infusion. Subsequently, hyper-hydration and uromitexan were continued IV or orally at home in the next day. G-CSF 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 at least 3x106 CD34+/Kg. Data about any adverse events (AEs) (type and grade) and/or hospitalization due to AEs were accurately collected.ResultsMedian age at diagnosis was 57 y (range 34-68). MM isotype was IgG, IgA, light chain, IgD/IgM/non-secretory respectively in 58.6, 18.2, 20.6 and 2.6%; ISS was 1/2/3 in 58.4/23/18.6%. Bone disease was detectable in 79.9% of pts, with 59.4% having 3 or more osteolysis. Median bone marrow plasma cell was 60%.Pts received induction with bortezomib (73.4%), IMiDs (5.1%), carfilzomib+IMiDs (12.5%) or cht, mostly VAD (9%). Second line therapy before mobilization was required by 5.1% of pts. Response prior of mobilization was CR/sCR, VGPR, PR, MR/SD/PD respectively in 14, 49.1, 34.5 and 2.4%.Stem cell collection was successful (at least 3x106/Kg CD34+ cells) in 93.1% of pts, with a median CD34+ cells harvest of 8.7x106/Kg (range 1.8-67.7). Target for 2 ASCT (at least 6x106/Kg CD34+ cells) was reached by 76.3% of pts. Administration of Plerixafor on demand was necessary in 12.1% of pts. After mobilization, 91.3% of pts proceeded to single (52.3%) or double (39%) ASCT.Cht was very well tolerated with 16.6% of pts having all-grade adverse events (AEs) and only 1.2% grade 3-5 (table 2). Most frequently AEs were nausea and vomiting grade 1-2 (6.8%). 1.7% of pts experienced cystitis (only grade 1-2) and 4% of pts infections (1 pt grade 5 with LD-CY). Other AEs (6.9%) were grade 1-2 and aspecific; only of note a pt presented a sudden appearance of 7th cranial nerve deficit at the end of ID-CY with negative imaging and resolution in few hours, interpreted as transient ischemic attack not correlated with Cy. Only 5.7% of pts required hospitalization for AEs, mainly infection.With the limit of retrospective setting, we compared LD and ID-CY with the incidence of AEs overall (14 vs 18%), AEs grade 3-5 (1.5 vs 1%) and hospitalization rate (1.5 vs 8.5%). We evaluated also median harvest (6.6 vs 10.9 x106/Kg CD34+ cells), percentage of pts reaching the target for 1 (87 vs 95%) and 2 (53 vs 89%) ASCT and plerixafor need (21 vs 6%). (Table 3).ConclusionIn conclusion, outpatient mobilization with L- and ID-CY appears an efficient and safe procedure, with minimal and manageable AEs and low rate of hospitalization. ID respect to LD-CY seems to be associated to a slight increase only in grade 1-2 AEs, however with a better stem cell yield and with a lower need of Plerixafor. Outpatient mobilization could ameliorate quality of life of pts and reduce costs, avoiding or minimizing the hospitalization rate, without compromising the safety profile and the success of PBSC collect. [Display omitted] DisclosuresRambaldi:Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy; Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses.

The Efficacy and Safety of Chemotherapy-Based Stem Cell Mobilization in Multiple Myeloma Patients Who Are Poor Responders to Induction: The Mayo Clinic Experience

We report the outcomes of 117 patients with newly diagnosed multiple myeloma who received novel agent induction, had a poor response to induction, and were mobilized using intravenous intermediate-dose cyclophosphamide (82%) or VD-PACE (18%) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor. The median progression-free survival and overall survival of the chemo-mobilized cohort were 21 months (95% confidence interval [CI], 15–71) and 58 months (95% CI, 47–80), respectively. We compared our cohort to a 117-patient cohort matched by the level of response at pretransplant evaluation. The matched patients were mobilized with G-CSF and on-demand plerixafor without chemotherapy. Patients receiving chemo-mobilization had higher stem cell yields than the growth-factor-only cohort (median, 10.7 × 106 cells/kg vs. 8.77 × 106 cells/kg, respectively; P < .001). The safety profile of chemo-mobilization was favorable, and there was no difference between the two groups in length of hospitalization during autologous stem cell transplantation (P = .95), days to neutrophil engraftment (P = .22), days to platelet engraftment (P = .27), or risk of bacteremia (P = .52). Twenty-nine percent of the chemo-mobilized cohort and 65% of the matched cohort required plerixafor for adequate mobilization (P < .001). Chemo-mobilization enhances stem cell collection without adversely impacting the post-transplant clinical course.

Chemotherapy-based stem cell mobilization in multiple myeloma patients treated with novel agents: The Mayo Clinic experience.

e20000 Background: In the novel agents’ era, refractoriness to induction in Multiple Myeloma (MM) is relatively rare. This population remain an unmet need and are often excluded from clinical trials. In the current era, chemotherapy-induced stem cell collections are used at Mayo Clinic in “poor responders” to induction, such as patients that progress prior to ASCT or patients with significant disease burden after induction. Methods: This is a retrospective study that includes all MM patients the underwent chemo-mobilization between January 2012 and September 2020 at Mayo Clinic. We compared our cohort to a cohort of 125 matched patients that were transplanted over the same time period and underwent mobilization with G-CSF and “on-demand” plerixafor. We matched the cohorts by level of response by IMWG at pre-transplant evaluation. Results: 125 newly diagnosed MM patients who received novel agents’ induction and had a poor response to induction were mobilized using IV intermediate-dose cyclophosphamide (83%) or VDT-PACE (17%) plus G-CSF and “on-demand” plerixafor. The median PFS and OS of the chemo-mobilized cohort were 16 months (95% CI 11-20) and 47 months (95% CI 37-71), respectively. Patients receiving chemo-mobilization had higher stem cell yields than the growth factor only cohort (median 9.88X106 cells/kg versus median 8.77X106 cells/kg, respectively (P&lt;0.001)). The safety profile of chemo-mobilization was favorable, with no difference between the two groups in length of hospitalization during ASCT (P=0.95), days to neutrophil or platelet engraftment, and risk of bacteremia (P=0.38). 29% of the chemo-mobilized cohort and 66% of the matched cohort required plerixafor for adequate mobilization (P&lt;0.001). Conclusions: Chemo-mobilization enhances stem cell collection in MM patients with a suboptimal response to induction and reduces the need for plerixafor without adversely impacting the post-transplant clinical course. [Table: see text]

A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis

BackgroundUpfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand. MethodsA prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 106/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session. ResultsMobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ μL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 106/kg vs 5.8 × 106/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4–6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001). ConclusionsOur data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients. Clinical Trial RegistryEudract Number EudraCT 2013−004690-27.

Gemcitabine, Dexamethasone, Cisplatin +/- Rituximab (GDP +/- R) Is Highly Effective As a Mobilization Regimen in Relapsed or Refractory Lymphoma (COLLYM STUDY)

IntroductionIn relapsed or refractory aggressive lymphoma, LY.12 study demonstrated the noninferiority of GDP, in comparison with DHAP, regarding response rate and overall survival with less toxicity. Because GDP ± Rituximab (R) can be easily given in an outpatient setting, this protocol has become the standard of treatment in many centers. However, no data has been published on the method to mobilize stem cells after GDP. The primary objective of the study was to describe the optimal method for a peripheral blood stem cell mobilization following GDP ± R and compare GDP ± R with intermediate-dose cyclophosphamide (ID-CY) as a secondary objective.MethodWe performed a retrospective observational multicenter study in a cohort of patients treated in one of the three centers located in Montreal and Quebec (CHUM, HMR, HEJ). The study was approved by each local IRB. The inclusion criteria were patients ≥ 18 years with a relapsed of refractory lymphoma who received GDP ± R as a salvage regimen before an autologous stem cells transplantation (ASCT) and who were mobilized on either GDP ± R or ID-CY without the use of plerixafor from January 1st 2014 to April 30th 2017. The GDP regimen consisted of gemcitabine 1000 mg/m2 IV on days 1 and 8, cisplatin 75 mg/m2 on day 1 and dexamethasone 40 mg once daily on day 1 to 4. Data were collected through the patient electronic health records in each hospital. The primary outcome was to define the percentage of patients achieving ≥ 2 x 106 CD34+/kg, the median CD34 yield, the number of days of apheresis and the initial day of apheresis following GDP ± R plus granulocyte-colony stimulating factor (G-CSF). For the secondary outcome, the same parameters were compared with ID-CY. Continuous and nominal variables were compared using Student's t-test and chi-square test respectively.ResultsA total of 27 patients with a median age of 54 years received GDP ± R as a salvage therapy for DLBCL (41%), HL (44%) or follicular lymphoma (15%). G-CSF was started at a daily dose of 5 mcg/kg (52%) or 10 mcg/kg (48%) generally at day 9 or 10 and after 2 (67%) or 3 cycles (26%) of GDP ± R. At the first attempt, all patients (100%) achieved the target of ≥ 2 x 106 CD34+/kg with a median of 7.4 x 106 CD34+/kg (2.5-54.1). The median days of apheresis was 2 (1-5) started after a median of 6 days (± 2) following the beginning of G-CSF. In one of the centers (CHUM) a second day of apheresis was automatically planned because the dosage of CD34 in the collected bags was obtained only the next day. Only 1 patient (4%) consulted to the emergency for a slight bleeding at the jugular catheter in a context of thrombocytopenia in the 21 days following the mobilization. A total of 26 patients have proceeded to an ASCT and they had a neutrophils recovery after a median of 11 days (± 4). In the CHUM, 8 and 12 patients were collected following ID-CY and GDP ± R respectively. They were no difference between ID-CY and GDP ± R regarding the target ≥ 2 x 106 CD34+/kg (100 vs 100%, p=NS) but the mean number of CD34+ collected were significantly higher with GDP ± R (23.2 vs 9.6, p=0.02) in less time (2 vs 3 days, p=0.63). There is a trend toward less consultation to emergency and hospitalization within 21 days of mobilization in favor of GDP ± R (8.3% vs 25%, p=0.33). In the ID-CY group, 2 patients were hospitalized for a short follow-up after the removal of the jugular catheter in a context of thrombocytopenia and febrile neutropenia respectively.ConclusionThis study demonstrated the feasibility of performing a peripheral blood stem cell mobilization at day 15 following GDP ± R with G-CSF given at day 9 of the second or third cycle. It highly effective and represents a better option due to its simplicity of administration, low rate of hospitalization and low cost. DisclosuresAdam:Apobiologix: Honoraria; Novartis: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Honoraria; Abbvie: Consultancy, Honoraria; TEVA: Consultancy. Emond:Roche: Honoraria; Novartis: Consultancy, Honoraria; Genzyme: Consultancy; Lundbeck: Consultancy, Honoraria; Gilead: Consultancy; Jassen: Consultancy, Honoraria; Nycomed: Consultancy; Sanofi-Aventis: Consultancy. Leblanc:Sanofi Aventis: Consultancy. Doucet:Roche: Consultancy; Seattle Genetic: Consultancy; Abbvie: Consultancy; Merck: Consultancy; Jannsen: Consultancy; Lundbeck: Consultancy.

Cyclophosphamide‐induced hemorrhagic cystitis in young patients with solid tumors: A single institution study

Although hemorrhagic cystitis (HC) is a significant complication in young patients who undergo chemotherapy with cyclophosphamide (CPA), risk factors and supportive care to prevent HC are unclear. This study attempted to identify optimal supportive care to prevent CPA-induced HC. Patients (<30-year-old) with malignant solid tumors who had been treated with CPA-containing chemotherapy in inpatient treatment were eligible. Vigorous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) were used for prophylaxis of CPA-induced HC. We retrospectively analyzed 81 patients who had been treated with CPA-containing chemotherapy over (collectively) 486 cycles, and examined relationships between HC and various factors, especially CPA dosage, use of mesna, and fluid infusion volume/rate. HC occurred in four patients (4.9%) and five cycles (1%). When stratifying by doses and methods of administration of CPA, HC occurred in 3/323 low- and intermediate-dose (<1500mg/m2 /day) cycles and mesna was used in all three cycles with HC. Patients who were given mesna had a lower flow rate than those given hydration alone in the low- and intermediate-dose CPA (126 ± 25 vs 106 ± 16mL/m2 /h; P<0.01). All patients who received high-dose CPA (≥1500mg/m2 /day) were also given mesna and vigorous hydration (115 ± 16mL/m2 /h). Our supportive care measures may be effective in preventing CPA-induced HC. Patients who receive CPA doses<1500mg/m2 /day should get ≥125mL/m2 /h of infused fluid, regardless of mesna usage; those who receive of CPA ≥1500mg/m2 /day should also receive mesna and vigorous hydration.

Hematopoietic Stem Cell Collection in Multiple Myeloma Patients: Influence of the Lenalidomide-Based Therapy and Mobilization Regimen Prior to Auto-HSCT

Background. A prompt graft acceptance is essential for positive autologous hematopoietic stem cell transplantation (auto-HSCT) outcome in multiple myeloma patients (MM). Prompt and favourable hematopoietic regeneration is associated with CD34+ cell count in a transplant. Although the indicators of low autotransplant cellularity have been defined, the practical application of new drug products and HSC mobilization regimens strengthens the relevance of determining their influence on the transplant quality. Aim. To determine the factors that are associated with low efficacy of auto-HSCT in MM patients and to evaluate the impact of lenalidomide during induction period and of vinorelbine as a mobilization regimen on the prognosis. Materials &amp; Methods. The authors performed a retrospective analysis of autotransplant collection results in 68 MM patients treated with two mobilization regimens: 3 g/m&lt;sup&gt;2&lt;/sup&gt; cyclophosphamide with granulocyte colony-stimulating factor (G-CSF) and 30 mg/m&lt;sup&gt;2&lt;/sup&gt; vinorelbine with G-CSF. Mobilization was aimed at collecting not less than 2-4 х 10&lt;sup&gt;6&lt;/sup&gt; CD34+ cells per kg body mass. CD34+ cell count was determined by four-color analysis on the Cytomics FC 500 laser flow cytometer. Results. The analysis showed that age or MM immunochemical specificity were not associated with CD34+ cell count in the transplant. Prior lenalidomide treatment compared to therapy without immunomodulators (4.1 х 10&lt;sup&gt;6&lt;/sup&gt;/kg vs. 7.76 х 10&lt;sup&gt;6&lt;/sup&gt;/kg) tends to decrease CD34+ count (р = 0.066). Cyclophosphamide included into mobilization regimen compared to vinorelbine (3.96 х 10&lt;sup&gt;6&lt;/sup&gt;/kg vs. 6.8 х 10&lt;sup&gt;6&lt;/sup&gt;/kg) significantly increased CD34+ cell count (р = 0.022). Conclusion. The decrease of CD34+ cell count in the autotransplant of the MM patients treated with lenalidomide prior to auto-HSC collection, and a lower mobilization activity of vinorelbine provide a basis for a differentiated selection of mobilization regimens. Vinorelbine may be administered to patients with a single auto-HSCT, i.e. elderly people and patients with complete response. In case of substantial lena-lidomide treatment prior to auto-HSCT, intermediate-dose cyclophosphamide is preferred.

Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma: A cohort study.

The combination of intermediate-dose cyclophosphamide (ID-CTX) and granulocyte colony-stimulating factor (G-CSF) fails to mobilize peripheral blood stem cells (PBSCs) in approximately 20% of treated patients with multiple myeloma (MM).In this cohort study, patients with MM underwent PBSC mobilization with either an ID-CTX plus G-CSF plus recombinant human thrombopoietin (rhTPO) regimen (72 patients; TPO group), or an ID-CTX plus G-CSF regimen (70 patients; non-TPO group).In the TPO group, the median CD34+ harvest was 5.36 × 106 per kg of body weight (0.50–22.39 × 106 per kg of body weight), with a harvest success rate of 91.7% (66/72), and an excellence rate of 55.6% (40/72). In the non-TPO group, the median CD34+ harvest was 3.30 × 106 per kg of body weight (0.20–21.14 × 106 per kg of body weight), with a harvest success rate of 75.7% (53/70), and an excellence rate of 25.7% (18/70). The median count of the CD34+ cells collected, success rate of collection, and excellence rate of collection were significantly higher in the TPO group than in the non-TPO group (P=.0001, P=.01, and P = .0001, respectively). Time to granulocyte and platelet engraftment was faster among patients in the TPO group than that in those from the non-TPO group. No platelet engraftment delay (>21 days) was observed among patients in the TPO group, while 3 patients in the non-TPO group displayed delayed platelet engraftment.Adding rhTPO to the ID-CTX chemotherapy plus G-CSF regimen improved treatment efficacy in mobilizing PBSCs for autologous hematopoietic stem cell transplantation.

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

BackgroundIn 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).ObjectiveTo 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.Methods92 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.ResultsMedian 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.ConclusionIn 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. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Low-Dose Cyclophosphamide Plus Granulocyte Colony-Stimulating Factor As an Efficacious and Safe Peripheral Blood Stem Cell Mobilizing Regimen in Patients with Hematologic Malignancies

▪Introduction:Collection of adequate numbers of Hematopoietic Stem Cells (HSCs) is a prerequisite for proceeding to autologous bone marrow transplant. However, various studies have showed that approximately 5% to 40% of patients do not meet the minimum threshold of 2×106 CD34+ cells/kg that is associated with timely engraftment and better outcomes. There is little consensus over the optimal mobilization regimen for procurement of peripheral blood CD34 + stem cells (PBSCs). Studies comparing mobilization using high-dose cyclophosphamide(HD-CY) {5-7 g/m2} or intermediate dose cyclophosphamide (ID-CY) {3-4g/m2} plus G-CSF with low dose cyclophosphamide (LD-CY) {1-2g/m2) plus G-CSF have reported higher total PBSC yield with the former but at the cost of higher toxicity [Hiwase et al, Cytotherapy 2007]. Hence the significance of our study to evaluate the efficacy and safety of LD-CY plus G-CSF in the era of novel induction therapies, takes precedence in terms of optimal resource utilization.Methods:We retrospectively analyzed mobilization efficacy and need for supportive care in Myeloma and Lymphoma patients that received LD-CY (2g/m2) plus G-CSF (10µg/kg/day) as the preferred mobilization regimen. Patients treated with novel induction regimens only, with or without radiation were included. LD-CY was given on day 1 with MESNA. G-CSF was started Day +5 from LD-CY and continued until the completion of apheresis. We started to measure peripheral CD34+ (pCD34) when patient's white blood cell count recovered to >1000/µL. When the pCD34 count was ≥10/uL, apheresis was started.Results:Out of 21 patients analyzed, 14 (67%) were Myeloma, predominantly IgG subtype (71%) and 7(33%) Lymphoma predominantly Non-Hodgkins type (71%). Our study population comprised of 53% females, 81% Caucasians with median age of 59 years (30-66). 28.5% patients had radiation treatment in the past. Mean/Median lines of chemotherapy previously received were 2/1 (1-5).71% patients received Lenalidomide (57%) / Thalidomide (14%) based regimens for induction therapies. 52% patients had complete response at the time of chemo mobilization.Successful mobilization (defined as total CD34+ cells collected >2x106/kg) was significantly achieved in 95% patients with mean/ median collection of 12.4/11.5 x106 CD34+ cells/kg (20 out of 21 patients, One sample T- test with significance level, alpha =0.025 [one sided ]showed T statistic 5.36 with p-value <0.0001). First apheresis yielded at least 2 x10 6/kg CD34+ cells in 76 % patients with a mean/median of 5.8/3.8 x106/kg CD34+ cells. 66% of patients were found to be good mobilizers, defined as patients collecting ≥5 x106 CD34+ cells/kg in ≤2 days. 81% patients collected ≥5x106 CD34+ cells/kg and 57 % patients collected ≥10 x106 CD34+ cells/kg. Mean/Median Peak pCD34count was 97.7/60 cells/µL(2-488). Median number of aphereses was 2 (mean 2.6) with the mean and median time to apheresis being 11 days (9-15). None of the patients needed inpatient hospitalization or intravenous antibiotics during mobilization or had any complication related to immunosuppression. 14% and 19% of patients needed packed red blood cell and platelet transfusions respectively during the mobilization period. One Myeloma patient (4.8%) that failed mobilization had previously received five lines of chemotherapy including lenalidomide/thalidomide containing regimens and had stable disease at the time of mobilization. Interestingly, 61% of myeloma patients that successfully mobilized had received lenalidomide containing induction regimen (mean/median no. of cycles- 3.9/4[1-7])Conclusion:Our analysis shows that LD-CY plus G-CSF is efficacious to mobilize sufficient number of stem cells (>2x106 CD34+ cells /kg) in Myeloma and Lymphoma patients treated with novel agents, including the challenging sub-group of lenalidomide treated myeloma patients, with no infectious complications or morbidity noted during the entire period of mobilization. Therefore, we believe LD-CY plus G-CSF may overcome the negative effects of prior lenalidomide exposure on PBSC mobilization [Mark et al, Biol Blood Marrow Transplant 2008] and is superior in terms of optimal resource utilization compared to novel plerixafor based regimens [Chaudhary et al, J Clin Apher 2013]. Prospective studies involving CY based regimens will help elucidate the optimal dose of chemo-mobilization. DisclosuresNo relevant conflicts of interest to declare.

The effect of gradual increment in rhG-CSF dose on stem cell yields in patients with multiple myeloma mobilized with intermediate dose cyclophosphamide plus rhG-CSF

Cyclophosphamide along with recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a commonly used strategy for mobilization. However, the optimal timing for rhG-CSF initiation after cyclophosphamide has not been determined as conclusively as has the G-CSF dose. In this paper, we aimed to present gradual dose increment of rhG-CSF between the third day of mobilization and time to apheresis that is started with 5 μg/kg (from day 3 to day 7) and continued with 10 μg/kg (from day 8 to time to apheresis) for peripheral blood stem cell (PBSC) mobilization in multiple myeloma (MM) patients and its effect on stem cell yield and mobilization success. Data from 30 consecutive patients with MM who underwent PBSC mobilization between October 2011 and June 2013, were retrospectively reviewed. While twenty-eight of 30 patients (93.3%) were successfully mobilized, 2 patients (6.7%) had mobilization failure. The final median CD34+ cell dose harvested from the patients was 9.5×10(6)/kg. The median number of apheresis was 2.5 (range, 0-3). Twenty-four patients (80%) yielded >2×10(6) CD34+ cells/kg in one apheresis procedure. In conclusion, our regimen might be used to decrease the mobilization failure regarding the low dose rhG-CSF use and provide a cost effective strategy.

Comparable efficacy and lower cost of PBSC mobilization with intermediate-dose cyclophosphamide and G-CSF compared with plerixafor and G-CSF in patients with multiple myeloma treated with novel therapies

Studies comparing the efficacy and cost of stem cell mobilization with intermediate-dose CY (ID-CY) and G-CSF against plerixafor and G-CSF, specifically in multiple myeloma (MM) patients treated in the novel therapy era, are not available. Eighty-eight consecutive patients undergoing mobilization with ID-CY (3-4 g/m(2)) and G-CSF (n=55) were compared with patients receiving plerixafor and G-CSF (n=33). Compared with plerixafor, ID-CY use was associated with higher median peak peripheral blood CD34+ cell count (68 vs 160 cells/μL, P<0.001), and CD34+ cell yield on day 1 of collection (6.9 × 10(6) vs 11.7 × 10(6) cells/kg, P<0.001). Total CD34+ cell yield was significantly higher in the ID-CY patients (median collection 16.6 × 10(6) vs 11.6 × 10(6) cells/kg; P<0.001). ID-CY use was associated with significantly more frequent episodes of febrile neutropenia (16.3% vs 0%; P=0.02), intravenous antibiotic use (16.3% vs 3%; P=0.03) and hospitalizations (P=0.02). The average total cost of mobilization in the plerixafor group was significantly higher compared with the ID-CY group ($28 980 vs $22 504.8; P=0.001). Our data indicate robust stem cell mobilization in MM patients treated with novel agents, with G-CSF and either ID-CY or plerixafor. When compared with plerixafor, ID-CY-containing mobilization was associated with significantly lower average total mobilization costs.

Cyclophosphamide enhances antitumor efficacy of oncolytic adenovirus expressing uracil phosphoribosyltransferase (UPRT) in immunocompetent Syrian hamsters

Oncolytic viruses (OVs) are novel cancer therapeutics with great promise, but host antiviral immunity represents the hurdle for their efficacy. Immunosuppression by cyclophosphamide (CP) has thus been shown to enhance the oncolytic efficacy of many OVs, but its effects on OVs armed with therapeutic genes remain unknown. We have previously reported on the efficacy of AxE1CAUP, an oncolytic adenovirus (OAd) expressing uracil phosphoribosyltransferase (UPRT), an enzyme that markedly enhanced the toxicity of 5-fluorouracil (5-FU), in immunodeficient, Ad-nonpermissive nude mice. Here we explored the efficacy and safety of intratumoral (i.t.) AxE1CAUP/5-FU therapy and of its combination with CP for syngenic HaP-T1 pancreatic cancers in immunocompetent, Ad-permissive Syrian hamsters. AxE1CAUP infected, replicated, expressed UPRT, and increased the sensitivity to 5-FU in HaP-T1 cells in vitro. I.t. AxE1CAUP/5-FU treatment inhibited the growth of subcutaneous HaP-T1 allografts. The combination with high-dose CP inhibited serum Ad-neutralizing antibody formation, increased intratumoral AxE1CAUP replication and UPRT expression, and resulted in further enhanced therapeutic effects with 5-FU. Neither body weight nor histology of the liver and lung changed during these treatments. A clinically-approved, intermediate-dose CP also enhanced the efficacy of i.t. AxE1CAUP/5-FU treatment in these hamsters, which was not affected by preexisting immunity to the vector. These data demonstrate the excellent antitumor efficacy and safety of an OAd armed with a suicide gene in combination with CP for treating syngenic tumors in immunocompetent, Ad-permissive animals, indicating the efficacy of CP in overcoming the hurdle of antiviral immunity for effective OV-mediated gene therapy.

A Multicenter Analysis of Intermediate-Dose Cyclophosphamide Versus Plerixafor and Granulocyte Colony Stimulating Factor for PB Progenitor Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Chemotherapies

A Multicenter Analysis of Intermediate-Dose Cyclophosphamide Versus Plerixafor and Granulocyte Colony Stimulating Factor for PB Progenitor Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Chemotherapies

Intermediate-Dose Cyclophosphamide Versus Plerixafor and Granulocyte Colony Stimulating Factor (G-CSF) for Peripheral Blood Progenitor Cell (PBPC) Mobilization in Patients with Multiple Myeloma (MM) Treated with Novel Induction Chemotherapies – A Multicenter Analysis

AbstractAbstract 4409 Introduction:PBPC mobilization with intermediate-dose cyclophosphamide (3–4 gm/m2) (ID-CY) and G-CSF when compared to low-dose CY (1–2 gm/m2)-based strategies, has been shown to have a favorable risk/benefit profile in MM patients (pts) receiving novel induction therapies (Hamadani M. BBMT 2012). However the relative efficacy of ID-CY as compared to plerixafor in PBPC mobilization in MM pts is not known. Herein we report outcomes of ID-CY/G-CSF mobilization compared to plerixafor/G-CSF mobilization in MM pts treated with novel induction regimens. Methods:This multicenter outcomes study includes 84 pts who underwent a planned, single autograft within 1-year of starting induction therapy with novel chemotherapy agents (thalidomide, lenalidomide, bortezomib) from 2003–2012. Consecutive pts undergoing mobilization with ID-CY/G-CSF (3–4 gm/m2) (n=55) at one institution were compared against consecutive pts receiving plerixafor/G-CSF (0.24 mg/kg) (n=29) at a different transplant center. At baseline the two groups were compared for parameters predicting mobilization failure. In order to assess efficiency of PBPC mobilization, we evaluated peak peripheral blood (PB) CD34+ cell counts, CD34+ cell yield on day1 of collection, total CD34+ cell collection, and total number of apheresis sessions. Mobilization failure was defined as failure to collect ≥2 ×106 cells/kg body weight. All pts with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was ≥2 mg/dl). Results:At baseline, the ID-CY and plerixafor cohorts were well balanced (Table 1). No difference was observed in the use of lenalidomide (p=0.3). Compared to plerixafor, ID-CY use was associated with higher median peak PB CD34+ cell count (63/μl vs. 160/μl, p=0.01), CD34+ yield on day 1 of collection (6.5 ×106/kg vs. 11.7 ×106/kg, p=0.004), and total CD34+ cell yield (10.5 ×106/kg vs. 24.9 ×106/kg, p=0.001). Median numbers of apheresis sessions were 2.2 in each group (p=0.9). No mobilization failures were seen in either group. There was no difference in the proportion of pts collecting ≥5×106/kg CD34+ cells in either group (93% vs. 96%, p=0.6), but more pts in ID-CY cohort collected ≥10×106/kg CD34+ cells (55% vs. 78%, p=0.02). Neutrophil engraftment was significantly faster (9.9 days vs. 13.1 days, p<0.001) in the ID-CY pts, likely because of higher infused CD34+ cell dose. Rate of adverse events were higher in the ID-CY cohort including neutropenic fevers (p=0.02), intravenous antibiotic use (p=0.03), hospitalization (p=0.05) and packed red cell transfusions (p=0.007). Conclusion:In the era of novel agents compared to plerixafor, ID-CY produced a more robust PBPC mobilization, faster engraftment, but was associated with significantly higher (but manageable) toxicity, and no difference in mobilization failure rates. These data support use of either ID-CY or plerixafor-based PBPC mobilization in MM pts undergoing stem cell collection following novel induction therapies. [Display omitted] Disclosures:Awan:Allos Therapeutics: Speakers Bureau. Hamadani:Conquer Cancer Foundation of ASCO: Research Funding; ASBMT & Millennium New Investigator Award: Research Funding; American Cancer Society 116837-IRG-09–061-01: Research Funding; Celgene Corp: Speakers Bureau.

Intermediate-Dose versus Low-Dose Cyclophosphamide and Granulocyte Colony-Stimulating Factor for Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Therapies

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide (ID-CY) and granulocyte colony-stimulating factor (G-CSF) has been shown to be more efficacious, albeit more toxic, than low-dose cyclophosphamide (LD-CY) mobilization regimens in patients with multiple myeloma treated with conventional therapies. However, the relative importance of cyclophosphamide dose intensity in peripheral blood progenitor cell mobilization after novel induction regimens is not known. Here we report mobilization outcomes of 123 patients who underwent transplantation within 1 year of starting induction chemotherapy with novel agents. We compared consecutive patients undergoing mobilization with ID-CY/G-CSF (3-4 g/m(2)) at one institution (n = 55) with patients receiving LD-CY/G-CSF (1.5 g/m(2)) at a different transplantation center (n = 68). At baseline, the 2 groups were well balanced, except for more frequent previous lenalidomide use in the ID-CY group (P = .04). Compared with LD-CY, ID-CY use was associated with higher median peak PB CD34(+) cell count (35/μL versus 160/μL; P < .001), CD34(+) cell yield on day 1 of collection (2.6 × 10(6)/kg versus 11.7×10(6)/kg, P ≤ .001), and total CD34(+) cell yield (7.5 × 10(6)/kg versus 16.6 × 10(6)/kg; P ≤ .001). Six patients in the LD-CY group had mobilization failure, compared with no patients in the ID-CY group. A significantly higher proportion of patients in the LD-CY group (P < .001) were unable to collect ≥5 × 10(6)/kg and ≥10 × 10(6)/kg CD34(+) cells. Neutrophil and platelet engraftment were significantly faster in the ID-CY group, likely because of higher infused CD34(+) cell doses. In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY-containing mobilization strategies in patients with multiple myeloma undergoing stem cell collection after novel induction regimens.

Intermediate- Versus Low-Dose Cyclophosphamide and Granulocyte Colony Stimulating Factor for Peripheral Blood Progenitor Cell Mobilization in Patients with Multiple Myeloma Treated with Novel Induction Chemotherapies – A Multicenter Analysis

Abstract 313 Introduction:Peripheral blood progenitor cell (PBPC) mobilization with intermediate-dose cyclophosphamide (3–4 gm/m2) (ID-CY) and G-CSF has been shown to be less toxic than high-dose CY (≥7 gm/m2) -based, and more efficacious than low-dose CY (LD-CY) (1–2 gm/m2) -based mobilization regimens in multiple myeloma (MM) patients following conventional induction regimens. However the relative importance of CY dose intensity in PBPC mobilization following novel induction regimens is not known. Herein we report comparative efficacy of PBPC mobilization in MM patients following novel induction chemotherapies, relative to CY dose intensity. Methods:This multicenter outcomes study includes 123 patients who underwent a planned, single autograft within 1-year of starting induction chemotherapy with novel chemotherapy agents (thalidomide, lenalidomide, bortezomib), from 2003–2010. Consecutive patients undergoing mobilization with ID-CY/G-CSF (3–4 gm/m2) (n=55) at one institution were compared against consecutive patients receiving LD-CY/G-CSF (1.5 gm/m2) (n=68) at a different transplant center. At baseline the two groups were compared for parameters predicting mobilization failure. In order to assess efficiency of PBPC mobilization, we evaluated peak peripheral blood (PB) CD34+ cell counts, CD34+ cell yield on day1 of collection, total CD34+ cell collection, and total number of apheresis sessions. Mobilization failure was defined as failure to collect ≥2 ×106cells/kg body weight. All patients with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was >2 mg/dl). SPSS version 13.0 was used for statistical analysis. Results:At baseline, the ID-CY and LD-CY cohorts were well balanced respectively in terms of mean age (57-yrs vs. 59-yrs, p=0.3), gender (males; 66% vs. 58%, p=0.4), high-risk cytogenetics (p=0.6), prior radiation (34% vs. 18%, p=0.06), disease stage (p=0.5), number of prior therapies (p=0.5) and remission status (p=0.2). No difference was observed in the types of novel therapies received prior to transplant (p=0.2), except 22% of the patients received lenalidomide in LD-CY vs. 40% in the ID-CY group (p=0.04). Compared to LD-CY, ID-CY use was associated with higher median peak PB CD34+ cell count (35/ul vs. 160/ul, p<0.001), CD34+ yield on day 1 of collection (2.6 ×106/kg vs. 11.6 ×106/kg, p=<0.001), total CD34+ cell yield (7.7 ×106/kg vs. 24.9 ×106/kg, p=<0.001), and a trend towards fewer apheresis sessions (p=0.052). Three patients in the LD-CY group had mobilization failure, while no patient in the ID-CY group had mobilization failure. Significantly higher proportion of patients (27% vs. 3.6%, p=<0.001) were unable to collect >5×106/kg CD34+ cells in LD-CY group. Neutrophil engraftment was significantly faster (15.4 days vs. 9.9 days) in the ID-CY patients, likely because of higher infused CD34+ cell dose. Conclusion: In conclusion, compared with LD-CY, ID-CY produced a more robust PBPC mobilization, in all parameters analyzed. These data caution against the use of LD-CY containing mobilization strategy in MM patients undergoing stem cell collection following novel induction regimens. Disclosures:No relevant conflicts of interest to declare.