Impact of the Use of Bendamustine Immediately before the Collection of Hematopoietic Stem Cells in Lymphoma. a Study By the Geltamo Group

Introduction: Bendamustine is a hybrid alkylating agent with high efficacy in different haematological malignancies, especially for lymphomas. Data about the capacity of peripheral blood stem cell (PBSC) mobilization or a possible stem cell toxicity after the use of bendamustine are unclear, with sufficient number of PBSC after bendamustine- rituximab (B-R) combination used in first line but with scarce information in relapse, especially with the use of bendamustine immediately before mobilization. The aim of this study was to evaluate the influence on PBSC mobilization of bendamustine as the last previous regimen used before the collection of PBSC. Methods: This is a retrospective, multicentre study, which includes patients from 8 different GELTAMO centres in Spain. Forty-eight lymphoma patients who received bendamustine followed immediately by stem cell mobilization (SCM) were included. A single-centre control group of consecutive patients was included, matched by histology, age and number of previous lines; HIV+ patients were excluded. Results: We included 83 patients, 45 in the bendamustine group and 38 in the control group. Table 1 shows patient´s characteristics. Both groups are adequately balanced. No patients received previous lenalidomide, and none patient had previous transplant. In the bendamustine group, the median number of cycles administered was 4 (range 2-6). In 8 patients of the bendamustine group and 12 in the control group the mobilization was programmed after first-line treatment. In the remaining cases, mobilizations were performed after 1 st or 2 nd relapse treatment. In most of the patients, the mobilization regimen was performed only with G-CSF, although 7 patients in the control and 3 patients in bendamustine groups received alternative regimens such as ESHAP, DHAP or ICE. Ten patients in the bendamustine group received plerixafor as part of the 1 st attempt mobilization regimen. Median number of apheresis with the first attempt of mobilization was 1.5 in the bendamustine group vs 1.3 in the control group. In bendamustine group 8 patients didn't go to apheresis due to a low pre-mobilization CD34+ cell count in peripheral blood, compared with 2 patients in control group. Median pre-mobilization CD34+ cells and median number of mobilized CD34 cells obtained was significative lower with in bendamustine group (Table 1). Moreover, 10 patients in this group didn't mobilized with 1 st attempt (and in 4 of them and neither with the second mobilization attempt), compared with only 2 in the control group. Mobilization failure in the bendamustine group was more frequent in certain lymphoma subtypes (among the 10 failures, HL and FL were the most frequent, 40%, p=0.07, and 50%, p=0.051 respectively), and was also associated with number of previous lines of therapy (HR 4,1; p= 0.041), since 90% of the failures were patients mobilized at relapse, and only 1 as 1st line consolidation. No relationship was found between stage, doses, or number of cycles of bendamustine administered. Conclusion: Our results show that the collection of sufficient numbers of PBSC could be affected by the use of bendamustine immediately prior to mobilization, especially in more pre-treated patients. We continue working on expanding our series to confirm these results. Figure 1 Figure 1. Disclosures Bastos-Oreiro: Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Salar: Roche: Consultancy, Speakers Bureau; Gilead: Research Funding; Janssen: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau.

Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis

Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) is a common regimen for PBSC mobilization; their benefits and risks are controversial. To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies; a total of 2770 patients with MM were analyzed. The CTX plus G-CSF regimen had higher yields of total CD34+ cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2 × 106/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4 × 106/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable event-free survival (EFS) (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality was consistent (p = 0.26). The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.

Outcomes of GCSF and Pre-Emptive Plerixafor Based Peripheral Blood Stem Cell Mobilization Among Patients with Multiple Myeloma-Experience from Newly Established Transplant Unit in Eastern Mediterranean Area

Introduction Granulocyte Colony Stimulating Factor (GCSF) with cyclophosphamide based peripheral blood stem cell (PBSC) mobilization is a widely used strategy among patients with multiple myeloma (MM), however, it is associated with toxicity and morbidity including severe infectious complications needing hospitalization. Plerixafor with GCSF has been widely used for mobilization as a preemptive strategy or during second attempt at collection with encouraging results. Methods We describe our experience from a newly established transplant unit in the Eastern Mediterranean region. A retrospective chart review was done and all consecutive patients of MM who underwent PBSC mobilization by GCSF and plerixafor between 2017 to 2020 were included in the study. Patients received GCSF (filgrastim, 10 µg/kg/day) and if peripheral blood CD34 count was less than 20/µl on day 4, patients received the first dose of plerixafor (240 µg/kg/day) on the evening of Day 4. Daily apheresis started on Day 5 for a maximum of 4 days, or until enough stem cells collected for one or two transplants at physician's discretion. Results A total of seventeen PBSC collections were carried out among patients with myeloma (n=17). There were 10 males and 7 females. The median age was 53 years (range 38-71), and 8/17 were less than 50 years of age. 14/ 17 were of IgG myeloma subtype, 2/17 were light chain myeloma, 1/17 was IgA myeloma type. 6/17 patients had R-ISS stage 3 disease while rest (11/17) had R-ISS stage 2 disease. 15/17 patients were in first remission. Only 1/17 patients had high-risk cytogenetics. 12/17 patients had bortezomib based therapy while 5/17 had lenalidomide based therapy. 13/17 patients had GCSF alone mobilization while 4/17 had GCSF plus pre-emptive plerixafor. 9/17 had a single collection while 8/17 had 2 collections. All patients on plerixafor needed two collections. Median CD34 stem cell dose was 8.6 x10^6 cells/kg (range 3.4-20 x 10^6 cells/kg). No grade 2-4 adverse events were recorded with this strategy post-collection and none required hospitalization for any adverse events. All patients underwent melphalan based conditioning and autologous stem cell transplant, although only 12/17 received a full dose of 200 mg/m2. 13/17 patients had fresh stem cells infused while the rest had cryopreserved stem cells. Median time to neutrophil recovery was 11 days (range 9-27) while median time to platelet recovery was 12 days (range 10-37). Day 100 mortality was zero percent. Conclusions Our study demonstrates successful collection with high stem cell yield enough for two stem cell transplants with GCSF and preemptive plerixafor strategy, in patients with MM, thus saving patients toxic effects of cyclophosphamide including cytopenias, infections which at times are severe causing morbidity and mortality. Over two-thirds of patients collected with GCSF alone. No major adverse events post stem cell collection were noted and all our patients engrafted early thus reducing hospital stay. Although the use of plerixafor increases cost but failure of mobilization, second mobilization, and infections (at times severe), delayed engraftment have their own costs and implications. Our study at our new transplant unit confirms that this pre-emptive strategy is safe, effective and reasonable chemo free first line option with no major adverse events as demonstrated by other studies. Disclosures No relevant conflicts of interest to declare.

Comparison of the efficiency, safety and survival outcomes in two stem cells mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis

Background Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM), it requires an adequate peripheral blood stem cells (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) are common regimens for PBSC mobilization, their benefits and risks are controversial. Methods To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies, a total of 2770 patients with MM analyzed. Results The CTX plus G-CSF regimen had higher yields of total CD34+ cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2x106/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4x106/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable EFS (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality were consistent (p = 0.26). Conclusions The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.

Risk Factors for PoorAutologous Peripheral blood Stem Cell Mobilization among Lymphoproliferative Disease Patients

Objective: Autologous peripheral blood haemopoietic stem cell (PBSC) transplantation is a standard therapeutic option for eligible patients with lymphoproliferative disease (LPD). The prerequisite for autologous PBSC transplantation is the successful stem cell mobilization. This study is aimed to determine the factors associated with poor PBSC mobilization in LPD patient at our center. Materials and methods: This retrospective record review involved 39 multiple myeloma (MM) and 92 of lymphoma patients who had undergone PBSC mobilization from January 2009 until December 2016. Patients were mobilized with combination chemotherapy and granulocyte colony stimulating factor. Factors affecting mobilization including patient’s, disease and treatment characteristics werestudied. Results: Majority of patients were Malay (93.9%) with the mean age at mobilization of 41.4 years. The mean of CD34+ cell dosage was 9.6x106 cells/kg. Successful and poor mobilization was found to be 90.8% and 9.2% respectively. Multivariate analysis showed that the significant risk factors for poor mobilization were age of ≥ 60 years (adjusted OR=38.43, p=0.005) and PB CD34+ cell count, <20 cells/uL (adjusted OR=132.69, p<0.001). Conclusion:PB CD34+ cell count and age ≥ 60years were the main risk factors for poor PBSC mobilization. Thus, alternative strategies of mobilization is needed to reduce risk of poor mobilization in a such group of patient. Bangladesh Journal of Medical Science Vol.19(3) 2020 p.458-466

Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield

There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF–mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 μg per day in obese and 900 μg per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.