Next Article in Journal
Evolving Applications of Circulating Tumor DNA in Merkel Cell Carcinoma
Previous Article in Journal
Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cancers
Volume 15
Issue 3
10.3390/cancers15030608
cancers-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study

by
Normann Steiner
1,*,
Georg Göbel
2,
Leonie Mauser
1,
Lena Mühlnikel
1,
Marie Fischinger
1,
Tina Künz
1,
Wolfgang Willenbacher
1,
Gabriele Hetzenauer
1,
Jakob Rudzki
1,
Walter Nussbaumer
3,
Wolfgang Mayer
3,
Eberhard Gunsilius
1,
Brigitte Kircher
1,
Dominik Wolf
1 and
David Nachbaur
1
1
Department of Internal Medicine V (Hematology and Medical Oncology), Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
2
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Schöpfstrasse 41/1, A-6020 Innsbruck, Austria
3
Central Institute for Blood Transfusion and Department of Immunology, University Hospital of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
*
Author to whom correspondence should be addressed.
Cancers 2023, 15(3), 608; https://doi.org/10.3390/cancers15030608
Submission received: 29 November 2022 / Revised: 11 January 2023 / Accepted: 17 January 2023 / Published: 18 January 2023
Browse Figures
Review Reports Versions Notes

Abstract

:

Simple Summary

Herein, we retrospectively analyze in our single-center study real-life data of 357 myeloma and lymphoma patients mobilized with granulocyte colony-stimulating factor plus a fixed dose of Plerixafor when indicated or G-CSF alone. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the G-CSF Group in the myeloma cohort. Lymphoma patients not requiring Plerixafor showed significantly faster neutrophil recovery, a trend for faster platelet recovery, and a significantly lower need for platelet transfusions. In myeloma patients, overall survival and progression-free survival after autologous stem cell transplantation were similar between the Plerixafor Group and the G-CSF Group, with hard to mobilize lymphoma patients showing significantly poorer progression-free survival and a trend also to lower overall survival.

Abstract

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies.

1. Introduction

Multiple myeloma, a malignant hematologic disease, occurs mainly in the elderly and remains mostly incurable even with the availability of new drugs such as proteasome inhibitors (PI), immunomodulatory drugs (IMiDs), and monoclonal antibodies [1,2]. Front line autologous stem cell transplantation ASCT for transplant eligible myeloma patients up to 75 years of age following PI- and/or IMiD-based induction is still the treatment of choice resulting in continuously improved progression-free and overall survival (PFS, OS) [3,4,5].
Autologous stem cell transplantation is also the treatment of choice for chemo-sensitive relapses of diffuse large B cell lymphoma (DLBCL) with durable remissions of about 40% and for early and late relapses in transplant-eligible patients with Hodgkin’s disease (HD) [6,7,8,9]. In addition, young patients with advanced mantle cell lymphoma (MCL) and selected patients with follicular lymphoma (FL) and T-cell non-Hodgkin’s lymphoma (T-NHL) might be candidates for early ASCT or at the time of sensitive relapse [10,11,12].
Since 2009, Plerixafor® (Mozobil) has been used in combination with G-CSF in poor mobilizers to improve the CD34+ cell yield [13]. Plerixafor, which is generally well tolerated, is an AMD300 bicyclic molecule and a selective and reversible CXCR4 antagonist and prevents its interaction with stroma-derived factor 1α, also known as CXCL12, resulting in an increased release of hematopoietic stem cells into the peripheral blood [14,15,16].
The aim of the present single-center study was to compare the outcome following ASCT in myeloma and lymphoma patients who needed Plerixafor for a successful stem cell mobilization procedure with the outcome in those myeloma and lymphoma patients who were successfully mobilized with G-CSF alone during the same time period.

2. Patients and Methods

2.1. Patients

Between 2009 and 2019, 360 consecutive patients were included in this retrospective single-center analysis. Detailed patient characteristics are listed in Table 1 and Table 2.
In the myeloma group, 108/211 (51%) patients and in the lymphoma group, 79/146 (54%) patients needed Plerixafor according to its labeled indication (additional administration of plerixafor was indicated in a CD34+ cell count ≤ 20 CD34+/μL in the peripheral blood (PB) on day 4 of mobilization with G-CSF alone or CD34+ cells remained ≤ 20 CD34+ cells/μL and no further increase was to be expected after chemo-mobilization despite administration of G-CSF for at least four days and a WBC ≥ 5.0 × 10 G/L, and if <1.0 × 106/kg CD34+ cells were collected after the first apheresis) and clinical and published experience [17,18] in addition to G-CSF alone (steady state mobilization) or chemotherapy plus G-CSF to guarantee an optimal stem cell yield for one ASCT defined as ≥ 2.0 × 106/kg CD34+ cells. The institutional standard dose for G-CSF was 7.5 µg administered subcutaneously bid and, when indicated, Plerixafor was used at a fixed dose of 24 mg administered subcutaneously late in the evening on day 4 to guarantee a delay of <11 h prior to the first or next leukapheresis. The conditioning regime for ASCT in myeloma patients was high-dose melphalan (100–200 mg/m²) and in lymphoma patients, the BEAM regime with all patients giving written informed consent. All myeloma patients but only 124/146 lymphoma patients proceeded to their first ASCT during the observation period (from 2009 until 2019). Neutrophil engraftment was defined as the first of two consecutive days with leukocytes ≥ 1.0 G/L and platelet engraftment was defined as the day of the last platelet transfusion. Approval for data collection and publication was obtained from the Ethics Committee of the Medical University of Innsbruck (vote # 1031/2020).

2.2. Study Endpoints

The primary study endpoints were neutrophil and platelet engraftment kinetics and transfusion requirements after ASCT in both myeloma and lymphoma patients. The secondary endpoints contained OS, PFS, and secondary malignancies in the two cohorts.

2.3. Statistical Methods

We used descriptive statistics to analyze the samples and outcomes of the lymphoma and myeloma patients stratified for plerixafor use or not. All event summaries refer to the first sign of disease relapse/progression (PFS) or death (OS). To evaluate differences between the strata, we used appropriate non-parametric tests as well as univariate and multivariate survival models (Kaplan–Meier curves, Log-rank test, Cox regression). The Kolmogorov–Smirnov test was applied for testing of distributions for continuous variables. We defined OS as the time from day of transplant to day of death or date of last follow-up. We further defined PFS as the timespan from day of transplant to date of disease relapse/progression or last follow-up. Only patients who received an ASCT were included for calculation of PFS and OS. As described in [19], we estimated unadjusted cumulative 36-month risks for mortality and progression defined as the probability of the event within three years after transplantation. Additionally, we provide crude incidence rates as the number of events divided by the total number of person-years at risk after transplantation with 95% confidence intervals (CIs) according to a Poisson distribution. Using Cox proportional hazards models, we examined the hazard ratio (HR) associations between disease relapse/progression or death and type of intervention. The time scale for calculation of the Cox proportional hazards models was months from the day of transplant. The proportional hazards assumption was tested by inspecting Kaplan–Meier curves and using Schoenfeld residuals. All tests for statistical significance were two-sided. p values less than 0.05 were considered statistically significant, and for point estimators, we provide 95% CIs. Statistical evaluation was performed using SPSS version 27.0 statistical software (SPSS, Chicago, IL, USA) and Stata version 17 (StataCorp, College Station, TX, USA).

3. Results

3.1. Efficacy of G-CSF +/− Plerixafor for Stem Cell Mobilization, Engraftment Kinetics, and Transfusion Requirements after ASCT

During the study period, 357/360 lymphoma and myeloma patients underwent a stem cell mobilization procedure at our institution. Three lymphoma patients receiving Plerixafor did not proceed to stem cell harvest and were therefore not included in the analysis. In the myeloma cohort, 108/211 (51%) patients required Plerixafor. The total median CD34+ cell number collected was 6.1 × 106/kg (IQR, 4.8–8.2) with no significant difference between myeloma patients requiring Plerixafor or not with a success rate within a single apheresis procedure of 75% in the Plerixafor (CD34+ cell number collected was 6.5 × 106/kg (IQR, 4.9–8.8)) and of 74% in the G-CSF Group (CD34+ cell number collected was 5.7 × 106/kg (IQR, 4.8–7.7)) (Table 3).
The overall success rate defined as ≥2 × 106/kg CD34+ cells in patients with lymphoma was 87% in the Plerixafor Group compared to 100% in the G-CSF Group (p = 0.003, Table 4.). A single apheresis procedure was sufficient in 67% of patients in the Plerixafor Group compared to 91% of those in the G-CSF Group (p < 0.001) (Table 4). Overall, Plerixafor led to a 7-fold increase in CD34+ cell numbers in peripheral blood in the entire cohort (myeloma and lymphoma patients) with a significantly greater increase in myeloma than in lymphoma patients (8-fold vs. 4-fold, p < 0.001).

3.2. Autologous Stem Cell Transplantation and Engraftment Kinetics

During the study period, 92% of successfully mobilized patients proceeded to ASCT, namely 96% myeloma and 85% lymphoma patients. Thirty patients, all in the Plerixafor Group, did not proceed to transplant either because of patient refusal, transplant ineligibility, or for other reasons.
The median CD34+ cell number re-transfused per transplant in myeloma patients was similar in both groups, whereas in lymphoma patients a significantly lower CD34+ cell number was re-transfused in the Plerixafor Group (p = 0.03, Table 3 and Table 4).
Virtually all patients received either G-CSF (30 µg/d subcutaneously) from day +7 or in the case of age and comorbidities, pegfilgrastim 6 mg subcutaneously on day +1 to accelerate neutrophil recovery (Table 3 and Table 4).
While in myeloma patients there were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the G-CSF Group, lymphoma patients not requiring Plerixafor showed significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions (Table 3 and Table 4).

3.3. Survival Outcomes and Secondary Malignancies

The 3-year OS in myeloma patients was 84% in both the Plerixafor Group and the G-CSF Group (p = 0.9) (Figure 1).
The 3-year PFS in myeloma patients requiring Plerixafor was 58% (95% CI, 49–65%) vs. 46% (95% CI, 37–55%) in the G-CSF Group (p = 0.2) (Figure 1).
The 3-year OS in lymphoma patients was 71% (95% CI, 59–80%) in the Plerixafor Group and 84% (95% CI, 76–89%) in the G-CSF Group (p = 0.1) (Figure 2).
The 3-year PFS in lymphoma patients mobilized with Plerixafor was 47% (95% CI, 34–60%) vs. 74% (95% CI, 65–81%) in the G-CSF Group (p = 0.003) (Figure 2).
During the observation period, eight myeloma patients (4%, four in each cohort; Plerixafor Group: one melanoma, one prostate cancer, one lung adenocarcinoma, one renal cell carcinoma; G-CSF Group: one Hodgkin’s lymphoma, two melanomas, and one t-AML) and six (5%) lymphoma patients developed a secondary malignancy after ASCT (five in the Plerixafor Group: one non-small-cell lung carcinoma, one myelodysplastic syndrome, three other lymphomas, and one in the G-CSF Group with a myeloproliferative neoplasm) (Table 3 and Table 4).

4. Discussion

Patients with multiple myeloma, who are transplant-eligible, undergo ASCT in first line setting with the goal of achieving better PFS and OS [20].
In contrast, patients with aggressive lymphoma usually do not undergo ASCT in first line therapy but in selected cases in the relapse setting (second or later line) to improve the outcome [21,22,23]. Thus, it is of utmost importance that a sufficient CD34+ cell collection count be achieved in the early disease phase followed by cryopreservation, regardless of whether ASCT is planned soon or later.
The present single-center analysis demonstrates that the addition of Plerixafor to G-CSF in so-called ‘poor mobilizers’ according to its labeled indication permitted 92% of all myeloma and lymphoma patients requiring ASCT, either as part of their frontline treatment or as salvage treatment for chemo-sensitive relapse in order to prolong PFS and OS, were able to be successfully mobilized to guarantee prompt engraftment after transplant. This goal was achieved within a single leukapheresis in 75% of myeloma and in 67% of lymphoma patients. Lymphoma patients mobilized with Plerixafor significantly more frequently required a second apheresis than did myeloma patients. The reason is probably due to the more intensive pre-treatment with at least two lines of chemotherapy including aggressive salvage regimes. Our findings are in line with the report published by Hübel et al., who analyzed European data of poor stem cell mobilizers and confirmed a lesser collection success for non-Hodgkin’s lymphoma patients than for myeloma and Hodgkin’s lymphoma patients. They also demonstrated the effectiveness of Plerixafor in poorly mobilized patients to increase the pool of patients for whom an autologous stem cell transplantation is a valid therapy option [13].
In our study, median time to neutrophil engraftment was similar in both myeloma groups. Our findings are in line with those of Worel et al. with no significant difference in time to neutrophil engraftment between the mobilization cohorts [24]. Prakash et al. observed faster neutrophil engraftment in patients mobilized with Plerixafor than in those in the pre-Plerixafor control group [25]. However, it should be noted that the mentioned study compared its findings with a historical control group with no possibility for Plerixafor administration. The fact that in our study no delay in neutrophil engraftment in myeloma patients was observed can certainly be attributed to the sufficient bone marrow function in patients who were not intensively pre-treated. However, in lymphoma patients mobilized without Plerixafor neutrophil engraftment was significantly faster than in patients receiving Plerixafor. Our findings are in line with those of Yuan et al., who observed significantly faster neutrophil engraftment in lymphoma patients mobilized without Plerixafor [26]. Other studies have described similar neutrophil engraftment kinetics, but they observed no statistically significant differences between the groups [27,28,29,30,31,32]. Median time of platelet engraftment in our study did not significantly differ in either of the mobilized myeloma groups and is in line with that of other authors [24,25]. This can also be explained by the sufficient bone marrow function in patients who did not undergo intensive pre-treatment.
Tricot et al. reported fast recovery of platelets within 14 days after high-dose cyclophosphamide and less than 12 months of prior chemotherapy as predictors of early engraftment [33].
On the other hand, lymphoma patients mobilized without Plerixafor showed a trend to faster engraftment. Results almost similar to our findings with a slight delay in the median time to platelet engraftment for the Plerixafor Group as compared to the control group were observed by Sureda and Yuan et al. [26,28]. Other reports showed similar platelet engraftment kinetics in the different mobilization lymphoma cohorts [29,30,31]. Importantly, in agreement with other studies, the cells collected after treatment with Plerixafor led to durable and fast neutrophil and platelet engraftment. Regarding the transfusion requirement, there were no significant differences in either of the mobilized myeloma groups. Our findings are in line with those of other authors with no significant differences in need of red cell or platelet transfusions [24,25].
However, a trend to higher transfusion requirements was observed in lymphoma patients mobilized with Plerixafor. The difference was not significant, admittedly, but could be explained as an expression of stem cell-toxic pretreatment in lymphoma patients. No significant differences in transfusion requirements in the different mobilization treatments were seen in other studies [24,26].
While there was no difference in OS or PFS in the myeloma cohort between patients requiring Plerixafor or not for successful stem cell mobilization, ‘hard to mobilize’ lymphoma patients requiring Plerixafor had a significantly poorer outcome regarding PFS and also a trend to poorer OS. In contrast to our data, Moreb et al. observed a significantly shortened PFS and OS in poorly as compared to well mobilized myeloma patients [34]. A reason for this difference can be the more aggressive disease biology, especially in poor mobilizers, including different risk factors for not sufficient mobilization with poorer outcome. Factors such as age >60, extensive prior treatment, thrombocytopenia, >1 line of induction treatment, prior radiation therapy, prior exposure to alkylating substances or melphalan and the prolonged use of lenalidomide are responsible for poor or suboptimal mobilization in myeloma patients [35,36,37,38,39] with the speculation that each risk factor results in cumulative effects for poor mobilization including poorer survival outcome. However, in the myeloma cohort, all these reflections argue against our results. Crocchiolo et al. observed a poorer outcome after allogeneic stem cell transplantation in myeloma and lymphoma patients with poor autologous mobilization status [40].
In our study, ‘hard to mobilize’ lymphoma patients showed a significantly poorer outcome for PFS and a trend to poorer OS. Our outcome findings are in line with those of other lymphoma studies, which showed in patients mobilized poorly with autologous stem cells a substantially shorter PFS and OS than in good mobilizers [28,32,41]. In our lymphoma cohort, the results can be explained by the advanced lymphoma disease and the larger number of patients included in the poor mobilizers cohort. Several risk factors for suboptimal or poor mobilization such as age over 60 years, progressive disease, bone marrow involvement, disease status and prior treatment, previous radiation, previous and type of chemotherapy, thrombocytopenia, neutropenic fever during the stem cell mobilization, failure of previous stem cell mobilization attempts, and patients not in remission after first line therapy are well known [13,41,42,43,44,45,46,47,48,49]. The presence of more than one of these factors including the lymphoma biology could be responsible for an unfavorable outcome.
Regarding the incidence of secondary malignancies after Plerixafor and G-CSF therapy, only marginal data are available. During our study, only 4% of myeloma patients in both treatment cohorts developed a secondary malignancy. Lymphoma patients treated with Plerixafor might tend to develop a secondary malignancy (6% in the Plerixafor Group, 1.5% in the G-CSF Group), although there was no statistical significancy. Our findings are in line with those of Doel et al. who observed five patients with a secondary malignancy, reflecting a cumulative incidence of 17% [50]. As data on the development of secondary malignancies in patients undergoing stem cell transplantation after mobilization with Plerixafor are very sparse, they need to be investigated in controlled prospective studies.
In summary, the significantly poorer outcome in lymphoma patients requiring Plerixafor in addition to G-CSF for a sufficient stem cell mobilization procedure regarding PFS, the slower engraftment kinetics and the greater transfusion requirements might suppose that these patients probably had a significantly higher and more stem cell-toxic pre-mobilization chemo-/radiotherapy burden and probably per se had more aggressive lymphoma subtypes. The lack of late graft failures and the low incidence of secondary malignancies in both the Plerixafor and G-CSF subgroups suppose no obvious functional differences between Plerixafor + G-CSF- or G-CSF-mobilized long-term repopulating hematopoietic stem cells when used for ASCT.

5. Conclusions

While there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor Group and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT.

Author Contributions

N.S. and D.N. conceptualized the project; N.S. and D.N. designed the methodology; N.S., D.N., G.G., T.K., M.F., L.M. (Leonie Mauser), and L.M. (Lena Mühlnikel) were involved in data curation, formal analysis, and investigation; N.S. and D.N. wrote the paper; W.W., G.H., J.R., W.N., W.M., E.G., B.K., and D.W. were involved in writing, review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Approval for data collection and publication was obtained from the Ethics Committee of the Medical University of Innsbruck (vote # 1031/2020).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The generated or analyzed data are available from the corresponding author on reasonable request.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Rollig, C.; Bornhauser, M. Multiple Myeloma. Lancet 2015, 385, 2197–2208. [Google Scholar] [CrossRef] [PubMed]
  2. Rajkumar, S. Multiple Myeloma: Every Year a New Standard? Hematol. Oncol. 2019, 37 (Suppl. S1), 62–65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Dhakal, B.; Szabo, A.; Chabra, S.; Hamadani, M.; D’Souza, A.; Usmani, S.; Sieracki, R.; Gyawali, B.; Jackson, J.; Asimakopoulos, F.; et al. Autologous Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction: A Systematic Review and Meta-Analysis. JAMA Oncol. 2018, 4, 343–350. [Google Scholar] [CrossRef]
  4. Attal, M.; Lauwers-Cances, V.; Hulin, C.; Leleu, X.; Caillot, D.; Escoffre, M.; Arnulf, B.; Macro, M.; Belhadj, K.; Garderet, L.; et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N. Engl. J. Med. 2017, 376, 1311–1320. [Google Scholar] [CrossRef] [PubMed]
  5. Gay, F.; Engelhardt, M.; Terpos, E.; Wäsch, R.; Giaccone, L.; Auner, H.; Caers, J.; Gramatzki, M.; van de Donk, N.; Oliva, S.; et al. From Transplant to Novel Cellular Therapies in Multiple Myeloma: European Myeloma Network Guidelines and Future Perspectives. Haematologica 2018, 103, 197–211. [Google Scholar] [CrossRef]
  6. Philip, T.; Guliemlmi, C.; Hagenbeek, A.; Somers, R.; Van der Lelie, H.; Bron, D.; Sonneveld, P.; Gisselbrecht, C.; Cahn, J.; Harousseau, J.; et al. Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin’s Lymphoma. N. Engl. J. Med. 1995, 333, 1540–1545. [Google Scholar] [CrossRef]
  7. Gisselbrecht, C.; Glass, B.; Mounier, N.; Singh Gill, D.; Linch, D.; Trneny, M.; Bosly, A.; Ketterer, N.; Shpilberg, O.; Hagberg, H.; et al. Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era. J. Clin. Oncol. 2010, 28, 4184–4190. [Google Scholar] [CrossRef] [Green Version]
  8. Crump, M.; Kuruvilla, J.; Couban, S.; MacDonald, D.; Kukreti, V.; Kouroukis, C.; Rubinger, M.; Buckstein, R.; Imrie, K.; Federico, M.; et al. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J. Clin. Oncol. 2014, 32, 3490–3496. [Google Scholar] [CrossRef] [Green Version]
  9. Philip, T.; Chauvin, F.; Armitage, J.; Bron, D.; Hagenbeek, A.; Biron, P.; Spitzer, G.; Velasquez, W.; Weisenburger, D.; Fernandez-Ranada, J.; et al. Parma International Protocol: Pilot Study of DHAP Followed by Involved-Field Radiotherapy and BEAC with Autologous Bone Marrow Transplantation. Blood 1991, 77, 1587–1592. [Google Scholar] [CrossRef] [Green Version]
  10. Dreyling, M.; Lenz, G.; Hoster, E.; Van Hoof, A.; Gisselbrecht, C.; Schmits, R.; Metzner, B.; Truemper, L.; Reiser, M.; Steinhauser, H.; et al. Early Consolidation by Myeloablative Radiochemotherapy Followed by Autologous Stem Cell Transplantation in First Remission Significantly Prolongs Progression-Free Survival in Mantle-Cell Lymphoma: Results of a Prospective Randomized Trial of the European MCL Network. Blood 2005, 105, 2677–2684. [Google Scholar] [CrossRef]
  11. Montoto, S.; Corradini, P.; Dreyling, M.; Ghielmini, M.; Kimby, E.; López-Guillermo, A.; Mackinnon, S.; Marcus, R.; Salles, G.; Schouten, H.; et al. Indications for Hematopoietic Stem Cell Transplantation in Patients with Follicular Lymphoma: A Consensus Project of the EBMT-Lymphoma Working Party. Haematologica 2013, 98, 1014–1021. [Google Scholar] [CrossRef] [PubMed]
  12. Smith, S.; Burns, L.; Besien, K.; LeRademacher, J.; He, W.; Fenske, T.; Suzuki, R.; Hsu, J.; Schouten, H.; Hale, G.; et al. Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma. J. Clin. Oncol. 2013, 31, 3100–3109. [Google Scholar] [CrossRef] [PubMed]
  13. Hübel, K.; Fresen, M.; Apperley, J.; Basak, G.; Douglas, K.; Gabriel, I.; Geraldes, C.; Jaksic, O.; Koristek, Z.; Kröger, N.; et al. European Data on Stem Cell Mobilization with Plerixafor in Non-Hodgkin’s Lymphoma, Hodgkin’s Lymphoma and Multiple Myeloma Patients. A Subgroup Analysis of the European Consortium of Stem Cell Mobilization. Bone Marrow Transpl. 2012, 47, 1046–1050. [Google Scholar] [CrossRef] [Green Version]
  14. Worel, N.; Rosskopf, K.; Neumeister, P.; Kasparu, H.; Nachbaur, D.; Russ, G.; Namberger, K.; Witt, V.; Schloegl, E.; Zojer, N.; et al. Plerixafor and Granulocyte-Colony-Stimulating Factor (G-CSF) in Patients with Lymphoma and Multiple Myeloma Previously Failing Mobilization with G-CSF with or without Chemotherapy for Autologous Hematopoietic Stem Cell Mobilization: The Austrian Experience on a Named Patient Program. Transfusion 2011, 51, 968–975. [Google Scholar] [CrossRef] [PubMed]
  15. Gerlach, L.; Skerlj, R.; Schwartz, T.; Bridger, G. Molecular Interactions of Cyclam and Bicyclam Non-Peptide Antagonists with the CXCR4 Chemokine Receptor. J. Biol. Chem. 2001, 276, 14153–14160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Matthys, P.; Hatse, S.; Vermeire, K.; Wuyts, A.; Bridger, G.; Henson, G.; De Clercq, E.; Billiau, A.; Schols, D. AMD3100, a Potent and Specific Antagonist of the Stromal Cell-Derived Factor-1 Chemokine Receptor CXCR4, Inhibits Autoimmune Joint Inflammation in IFN-Gamma Receptor-Deficient Mice. J. Immunol. 2001, 167, 4686–4692. [Google Scholar] [CrossRef] [Green Version]
  17. DiPersio, J.; Stadtmauer, E.; Nademanee, A.; Micaleff, I.; Stiff, P.; Kaufman, J.; Maziarz, R.; Hosing, C. Plerixafor and G-CSF versus Placebo and G-CSF to Mobilize Hematopoietic Stem Cells for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma. Blood 2009, 113, 5720–5726. [Google Scholar] [CrossRef]
  18. DiPersio, J.; Micaleff, I.; Stiff, P.; Bolwell, B.; Maziarz, R.; Jacobsen, E.; Nademanee, A.; McCarty, J.; Bridger, G.; Calandra, G. Phase III Prospective Randomized Double-Blind Placebo-Controlled Trial of Plerixafor Plus Granulocyte Colony-Stimulating Factor Compared With Placebo Plus Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Non-Hodgkin’s Lymphoma. J. Clin. Oncol. 2009, 27, 4767–4773. [Google Scholar] [CrossRef]
  19. Steiner, N.; Göbel, G.; Michaeler, D.; Platz, A.; Prokop, W.; Wolf, A.; Wolf, D.; Duftner, C.; Gunsilius, E. Rheumatologic Diseases Impact the Risk of Progression of MGUS to Overt Multiple Myeloma. Blood Adv. 2021, 5, 1746–1754. [Google Scholar] [CrossRef]
  20. Al Hamed, R.; Bazarbachi, A.; Malard, F.; Harousseau, J.; Mohty, M. Current Status of Autologous Stem Cell Transplantation for Multiple Myeloma. Blood Cancer J. 2019, 9, 44. [Google Scholar] [CrossRef]
  21. Josting, A.; Reiser, M.; Rueffer, U.; Salzberger, B.; Diehl, V.; Engert, A. Treatment of Primary Progressive Hodgkin’s and Aggressive Non-Hodgkin’s Lymphoma: Is There a Chance for Cure? J. Clin. Oncol. 2000, 18, 332–339. [Google Scholar] [CrossRef] [PubMed]
  22. Rancea, M.; Monsef, I.; von Tresckow, B.; Engert, A.; Skoetz, N. High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Patients with Relapsed/Refractory Hodgkin Lymphoma. Cochrane Database Syst. Rev. 2013, 6, CD009411. [Google Scholar] [CrossRef] [PubMed]
  23. Wullenkord, R.; Berning, P.; Niemann, A.; Wethmar, K.; Bergmann, S.; Lutz, M.; Schliemann, C.; Mesters, R.; Keßler, T.; Schmitz, N.; et al. The Role of Autologous Stem Cell Transplantation (ASCT) in Aggressive B-Cell Lymphomas: Real-World Data from a Retrospective Single-Center Analysis. Ann. Hematol. 2021, 100, 2733–2744. [Google Scholar] [CrossRef] [PubMed]
  24. Worel, N.; Fritsch, G.; Agis, H.; Böhm, A.; Engelich, G.; Leitner, G.; Geissler, K.; Gleixner, K.; Kalhs, P.; Buxhofer-Ausch, V.; et al. Plerixafor as Preemptive Strategy Results in High Success Rates in Autologous Stem Cell Mobilization Failure. J. Clin. Apher. 2017, 32, 224–234. [Google Scholar] [CrossRef]
  25. Prakash, V.; Malik, P.; Sahoo, R.; Pramanik, R.; Choudhary, P.; Varshney, A.; Kumar, L. Multiple Myeloma: Risk Adapted Use of Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplantation Is Effective and Cost Efficien. Clin. Lymphoma Myeloma Leuk. 2022, 22, 44–51. [Google Scholar] [CrossRef]
  26. Yuan, S.; Palmer, J.; Tsai, N.; Dagis, A.; Nademanee, A.; Wang, S. Engraftment and Outcomes Following Autologous Stem Cell Transplantation in Hodgkin Lymphoma Patients Mobilized with Plerixafor. Hematol. Oncol. 2017, 35, 281–287. [Google Scholar] [CrossRef]
  27. Mombled, M.; Rodriguez, L.; Avalon, M.; Duchez, P.; Vlaski-Lafarge, M.; Debeissat, C.; Pérard, B.; Sawai, K.; Pasquet, J.; Bijou, F.; et al. Characteristics of Cells with Engraftment Capacity within CD34+ Cell Population upon G-CSF and Plerixafor Mobilization. Leukemia 2020, 34, 3370–3381. [Google Scholar] [CrossRef]
  28. Sureda, A.; Chabannon, C.; Masszi, T.; Pohlreich, D.; Scheid, C.; Thieblemont, C.; Wahlin, B.; Sakellari, I.; Russel, N.; Janikova, A.; et al. Analysis of Data Collected in the European Society for Blood and Marrow Transplantation (EBMT) Registry on a Cohort of Lymphoma Patients Receiving Plerixafor. Bone Marrow Transpl. 2020, 55, 613–622. [Google Scholar] [CrossRef]
  29. Varmavuo, V.; Rimpiläinen, J.; Kuitunen, H.; Nihtinen, A.; Vasala, K.; Mikkola, M.; Kutila, A.; Lehtonen, P.; Kuittinen, T.; Mäntymaa, P.; et al. Engraftment and Outcome after Autologous Stem Cell Transplantation in Plerixafor-Mobilized Non-Hodgkin’s Lymphoma Patients. Transfusion 2014, 54, 1243–1250. [Google Scholar] [CrossRef]
  30. Hübel, K.; Ostermann, H.; Glaß, B.; Noppeney, R.; Kron, A.; Milkovich, G.; Mohty, M. Plerixafor in Non-Hodgkin’s Lymphoma Patients: A German Analysis of Time, Effort and Costs. Bone Marrow Transpl. 2019, 54, 123–129. [Google Scholar] [CrossRef]
  31. Mohty, M.; Azar, N.; Chabannon, C.; Le Gouill, S.; Karlin, L.; Farina, L.; Milkovich, G.; Ostermann, H.; Glaß, B.; Noppeney, R.; et al. Plerixafor in Poor Mobilizers with Non-Hodgkin’s Lymphoma: A Multi-Center Time-Motion Analysis. Bone Marrow Transpl. 2018, 53, 246–254. [Google Scholar] [CrossRef]
  32. Gordan, L.; Sugrue, M.; Lynch, J.; Wiliams, K.; Khan, S.; Wingard, J.; Moreb, J. Poor Mobilization of Peripheral Blood Stem Cells Is a Risk Factor for Worse Outcome in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation. Leuk. Lymphoma 2003, 44, 815–820. [Google Scholar] [CrossRef]
  33. Tricot, G.; Jagannath, S.; Vesole, D.; Nelson, J.; Tindle, S.; Miller, L.; Cheson, B.; Crowley, J.; Barlogie, B. Peripheral Blood Stem Cell Transplants for Multiple Myeloma: Identification of Favorable Variables for Rapid Engraftment in 225 Patients. Blood 1995, 85, 588–596. [Google Scholar] [CrossRef] [Green Version]
  34. Moreb, J.; Byrne, M.; Shugarman, I.; Zou, F.; Yiong, S.; May, W.; Norking, M.; Hiemenz, J.; Brown, R.; Cogle, C.; et al. Poor Peripheral Blood Stem Cell Mobilization Affects Long-Term Outcomes in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation. J. Clin. Apher. 2018, 33, 29–37. [Google Scholar] [CrossRef]
  35. Chua, C.; Lim, H.; Chai, K.; Ong, J.; Sim, S.; Wood, C.; Dickinson, M.; Campbell, P.; Hempton, J.; King, H.; et al. Peripheral Blood Stem Cell Mobilisation with G-CSF Alone versus G-CSF and Cyclophosphamide after Bortezomib, Cyclophosphamide and Dexamethasone Induction in Multiple Myeloma. Bone Marrow Transpl. 2018, 53, 1116–1123. [Google Scholar] [CrossRef] [Green Version]
  36. Bakeer, M.; Zubair, A.; Roy, V. Low Baseline Platelet Count Predicts Poor Response to Plerixafor in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Mobilization. Cytotherapy 2020, 22, 16–20. [Google Scholar] [CrossRef]
  37. Douglas, K.; Gilleece, M.; Hayden, P.; Hunter, H.; Johnson, P.; Kallmeyer, C.; Malladi, R.; Paneesha, S.; Pawson, R.; Quinn, M.; et al. UK Consensus Statement on the Use of Plerixafor to Facilitate Autologous Peripheral Blood Stem Cell Collection to Support High-Dose Chemoradiotherapy for Patients with Malignancy. J. Clin. Apher. 2018, 33, 46–59. [Google Scholar] [CrossRef]
  38. Zannetti, B.; Saraceni, F.; Cellini, C.; Fabbri, E.; Monaco, F.; Guarini, A.; Laszlo, D.; Martino, M.; Olivieri, A.; Imola, M.; et al. Low-Dose Cyclophosphamide versus Intermediate-High-Dose Cyclophosphamide versus Granulocyte Colony-Stimulating Factor Alone for Stem Cell Mobilization in Multiple Myeloma in the Era of Novel Agents: A Multicenter Retrospective Study. Transpl. Cell. Ther. 2021, 27, 244.e1–244.e8. [Google Scholar] [CrossRef] [PubMed]
  39. Wang, L.; Xiang, H.; Yan, Y.; Deng, Z.; Li, H.; Li, X.; Liu, J. Correction to: 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. Ann. Hematol. 2021, 100, 575. [Google Scholar] [CrossRef] [PubMed]
  40. Crocchiolo, R.; Chabannon, C.; El-Cheikh, J.; Esterni, B.; Lemarié, C.; Fürst, S.; Castagna, L.; Bouabdallah, R.; Ladaique, P.; Coso, D.; et al. Poor Autologous Mobilization Status Does Not Impact on Hematological Recovery but Affects Outcome after Allogeneic Stem Cell Transplant for Lymphoma and Myeloma. Leuk. Lymphoma 2013, 54, 417–420. [Google Scholar] [CrossRef] [PubMed]
  41. Pavone, V.; Gaudio, F.; Console, G.; Vitolo, U.; Iacopino, P.; Guarini, A.; Liso, V.; Perrone, T.; Liso, A. Poor Mobilization Is an Independent Prognostic Factor in Patients with Malignant Lymphomas Treated by Peripheral Blood Stem Cell Transplantation. Bone Marrow Transpl. 2006, 37, 719–724. [Google Scholar] [CrossRef] [Green Version]
  42. Wuchter, P.; Ran, D.; Bruckner, T.; Schmitt, T.; Witzens-Harig, M.; Neben, K.; Goldschmidt, H.; Ho, A. Poor Mobilization of Hematopoietic Stem Cells-Definitions, Incidence, Risk Factors, and Impact on Outcome of Autologous Transplantation. Bone Marrow Transpl. 2010, 16, 490–499. [Google Scholar] [CrossRef] [Green Version]
  43. Akhtar, S.; Weshi, A.; Rahal, M.; Khafaga, Y.; Tbakhi, A.; Humaidan, H.; Maghfoor, I. Factors Affecting Autologous Peripheral Blood Stem Cell Collection in Patients with Relapsed or Refractory Diffuse Large Cell Lymphoma and Hodgkin Lymphoma: A Single Institution Result of 168 Patient. Leuk. Lymphoma 2008, 49, 769–778. [Google Scholar] [CrossRef]
  44. Kuittinen, T.; Nousiainen, T.; Halonen, P.; Mahlamäki, E.; Jantunen, E. Prediction of Mobilisation Failure in Patients with Non-Hodgkin’s Lymphoma. Bone Marrow Transpl. 2004, 33, 907–912. [Google Scholar] [CrossRef]
  45. Mendrone, A.; Arrais, C.; Saboya, R.; Chamone, D.A.; Dulley, F. Factors Affecting Hematopoietic Progenitor Cell Mobilization: An Analysis of 307 Patients. Transfus. Apher. Sci. 2008, 39, 187–192. [Google Scholar] [CrossRef]
  46. Pusic, I.; Jiang, S.; Landua, S.; Uy, G.; Rettig, M.; Cashen, A.; Westervelt, P.; Vij, R.; Abboud, C.; Stockerl-Goldstein, K.; et al. Impact of Mobilization and Remobilization Strategies on Achieving Sufficient Stem Cell Yields for Autologous Transplantation. Biol. Blood Marrow Transpl. 2008, 14, 1045–1056. [Google Scholar] [CrossRef] [Green Version]
  47. Bensinger, W.; Appelbaum, F.; Rowley, S.; Storb, R.; Sanders, J.; Lilleby, K.; Gooley, T.; Demirer, T.; Schiffman, K.; Weaver, C. Factors that Influence Collection and Engraftment of Autologous Peripheral-Blood Stem Cells. J. Clin. Oncol. 1995, 13, 2547–2555. [Google Scholar] [CrossRef]
  48. Moskowitz, C.; Glassman, J.; Wuest, D.; Maslak, P.; Reich, L.; Gucciardo, A.; Coady-Lyons, N.; Zelenetz, A.; Nimer, S. Factors Affecting Mobilization of Peripheral Blood Progenitor Cells in Patients with Lymphoma. Clin. Cacer Res. 1998, 4, 311–316. [Google Scholar]
  49. Michallet, M.; Thiébaut, A.; Dreger, P.; Remes, K.; Milpied, N.; Santini, G.; Hamon, M.; Björkstrad, B.; Kimby, E.; Belhabri, A.; et al. Peripheral Blood Stem Cell (PBSC) Mobilization and Transplantation after Fludarabine Therapy in Chronic Lymphocytic Leukaemia (CLL): A Report of the European Blood and Marrow Transplantation (EBMT) CLL Subcommittee on Behalf of the EBMT Chronic Leukaemias Working Party (CLWP). Br. J. Haematol. 2000, 108, 595–601. [Google Scholar] [CrossRef]
  50. Deol, A.; Abrams, J.; Masood, A.; Al-Kadhimi, Z.; Abidi, M.; Ayash, L.; Lum, L.; Ratanatharathorn, V.; Uberti, J. Long-Term Follow up of Patients Proceeding to Transplant Using Plerixafor Mobilized Stem Cells and Incidence of Secondary Myelodysplastic Syndrome/AML. Bone Marrow Transpl. 2013, 48, 1112–1116. [Google Scholar] [CrossRef]
Cancers 15 00608 g001 550
Figure 1. Overall survival and progression-free survival of myeloma patients.
Figure 1. Overall survival and progression-free survival of myeloma patients.
Cancers 15 00608 g001
Cancers 15 00608 g002 550
Figure 2. Overall survival and progression-free survival of lymphoma patients.
Figure 2. Overall survival and progression-free survival of lymphoma patients.
Cancers 15 00608 g002
Table
Table 1. Multiple Myeloma patients and disease characteristics.
Table 1. Multiple Myeloma patients and disease characteristics.
Multiple Myeloma PatientsPlerixafor GroupG-CSF Groupp Value
Number of patients—N (%)108 (51)103 (49)
Age at diagnosis (years)—median [IQR]59 [52–64]55 [47–62]0.01
Gender 0.6
Male—N (%)63 (58)64 (62)
Female—N (%)45 (42)39 (38)
Bone marrow infiltration at diagnosis 0.4
Yes—N (%)91 (85)90 (88)
No—N (%)4 (4)3 (3)
n.a.13 (12)10 (10)
Disease stage at diagnosis (ISS) 0.9
ISS I—N (%)48 (44)46 (45)
ISS II—N (%)34 (32)28 (27)
ISS III—N (%)22 (20)24 (23)
n.a.—N (%)4 (4)5 (5)
Chemomobilization—N (%)0 (0)0 (0)
Prior lines of therapy 0.04
1—N (%)108 (100)97 (94)
2—N (%)0 (0)3 (3)
≥3—N (%)0 (0)3 (3)
Prior radiotherapy 0.2
Yes—N (%)39 (36)28 (27)
No—N (%)69 (64)75 (73)
Disease status at ASCT <0.001
CR, nCR, sCR—N (%)42 (39)16 (16)
VGPR—N (%)27 (25)36 (35)
PR—N (%)28 (26)26 (25)
SD—N (%)2 (2)1 (1)
PD—N (%)8 (7)5 (5)
n.a.—N (%)1 (1)19 (18)
nCR, near complete remission; sCR, stringent complete remission; CR, complete remission; VGPR, very good partial remission; PR, partial remission; SD, stable disease; PD, progressive disease; n.a., not available; G-CSF, granulocyte colony-stimulating factor.
Table
Table 2. Lymphoma patients and disease characteristics.
Table 2. Lymphoma patients and disease characteristics.
Lymphoma PatientsPlerixafor GroupG-CSF Groupp Value
Number of Patients —N (%) 82 (55)67 (45)
DLBCL29 (35)17 (25)
MCL10 (12)15 (22)
FL8 (10)5 (8)
HL9 (11)4 (6)
Burkitt’s lymphoma5 (6)6 (9)
AITL5 (6)3 (5)
TLBL7 (9)0 (0)
PTCL4 (5)2 (3)
Primary CNS lymphoma1 (1)4 (6)
Other B/T-NHL4 (5)11 (16)
Age at diagnosis (years)—median [IQR]52 [44–58]49 [41–57]0.4
Gender 0.8
Male—N (%)57 (70)45 (67)
Female—N (%)25 (30)22 (33)
Bone marrow infiltration at diagnosis 0.4
Yes—N (%)12 (15)16 (24)
No—N (%)48 (58)35 (52)
n.a.22 (27)16 (24)
Disease stage at diagnosis (Ann Arbor) 0.4
I–II N (%)18 (22)7 (11)
III–IV N (%)60 (74)42 (62)
n.a.—N (%)4 (5)18 (27)
Chemomobilization—N (%)82 (100)67 (100)
Prior lines of therapy 0.8
1—N (%)22 (27)16 (24)
2—N (%)43 (52)39 (58)
≥3—N (%)17 (21)12 (18)
Prior radiotherapy 0.8
Yes—N (%)11 (13)10 (15)
No—N (%)71 (87)57 (85)
Disease status at ASCT 0.08
CR—N (%)40 (49)29 (43)
PR—N (%)25 (30.5)21 (31)
SD—N (%)8 (10)1 (1.5)
Mixed response—N (%)0 (0)1 (1.5)
PD—N (%)2 (2)5 (8)
CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; n.a., not available; DLBCL, diffuse large B-Cell lymphoma; MCL, mantle cell lymphoma; FL, follicular lymphoma; HL, Hodgkin’s lymphoma; AITL, angioimmunoblastic T-Cell lymphoma; TLBL, T-Cell lymphoblastic lymphoma; PTCL, peripheral T-Cell lymphoma; NHL, non-Hodgkin’s lymphoma; G-CSF, granulocyte colony-stimulating factor.
Table
Table 3. CD34+ cell kinetics, engraftment, and outcome in multiple myeloma patients.
Table 3. CD34+ cell kinetics, engraftment, and outcome in multiple myeloma patients.
Multiple Myeloma PatientsPlerixafor GroupG-CSF Groupp Value
Number of stem cell mobilized patients—N (%)108 (51)103 (49)
Total number of CD34+ cells collected (×106/kg)—median [IQR]6.5 [4.9–8.8]5.7 [4.8–7.7]0.2
Total number of apheresis procedures 0.9
1—N (%)83 (77)78 (76)
2—N (%)19 (17.5)20 (19)
3—N (%)6 (5.5)5 (5)
Success defined as:
≥4 × 106/kg CD34+ cells—N (%)93 (86)98 (95)0.03
Success in a single apheresis procedure—N (%)81 (75)76 (74)0.8
Number of patients receiving a first ASCT100 (93)103 (100)0.02
Transplanted CD34+ cell number (×106/kg)—median [IQR]3.5 [2.7–4.9]3.8 [2.6–5.3]0.9
Time to neutrophil engraftment—median [range]12 [8–15]12 [9–20]0.9
Time to platelet engraftment—median [range]12 [8–25]11 [8–34]0.1
Number of red cell transfusions—median [range]1.5 [0–12]0 [0–10]0.6
Number of platelet transfusions—median [range]2 [0–14]2 [0–12]0.1
3-year progression-free survival—months % (95% CI)58 (49–65)46 (37–55)0.2
3-year overall survival—months % (95% CI)84 (77–89)84 (77–89)0.9
Secondary malignancies—N (%)4 (4)4(4)0.9
ASCT, autologous stem cell transplantation; G-CSF, granulocyte colony-stimulating factor. In lymphoma patients, the median total CD34+ cell number collected was 4.4 × 106/kg (IQR, 2.5–7.8) with a significantly lower CD34+ cell number harvested in patients requiring Plerixafor (3.3 vs. 5.6, p < 0.001) (Table 4).
Table
Table 4. CD34+ cell kinetics, engraftment, and outcome in lymphoma patients.
Table 4. CD34+ cell kinetics, engraftment, and outcome in lymphoma patients.
Lymphoma PatientsPlerixafor GroupG-CSF Groupp Value
Number of stem cell mobilized patients—N (%)79 (54)67 (46)
Total number of CD34+ cells collected (×106/kg)—median [IQR]3.3 [2.2–6.1]5.6 [3.4–11.0]<0.001
Total number of apheresis procedures 0.02
1—N (%)52 (66)58 (87)
2—N (%)24 (30)7 (10)
3—N (%)2 (3)2 (3)
4—N (%)1 (1)0 (0)
Success defined as:
≥2 × 106/kg CD34+ cells—N (%)69 (87)67 (100)0.003
Success in a single apheresis procedure—N (%)52 (67)60 (91)<0.001
Number of patients receiving a first ASCT—N (%)57 (79)67 (100)<0.001
Transplanted CD34+ cell number (×106/kg)—median [IQR]4.0 [2.4–6.2]5.2 [3.2–9.3]0.03
Time to neutrophil engraftment—median [range]11 [8–14]10 [8–16]0.0004
Time to platelet engraftment—median [range]13 [5–59]12 [5–17]0.04
Number of red cell transfusions—median [range]4 [0–24]2 [0–10]0.43
Number of platelet transfusions—median [range]5 [1–54]3 [1–20]0.01
3-year progression-free survival—months % (95% CI)47 (34–60)74 (65–81)0.003
3-year overall survival—months % (95% CI)71 (59–80)84 (76–89)0.1
Secondary malignancies5 (6)1 (1.5)0.1
ASCT, autologous stem cell transplantation; G-CSF, granulocyte colony-stimulating factor.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Steiner, N.; Göbel, G.; Mauser, L.; Mühlnikel, L.; Fischinger, M.; Künz, T.; Willenbacher, W.; Hetzenauer, G.; Rudzki, J.; Nussbaumer, W.; et al. Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study. Cancers 2023, 15, 608. https://doi.org/10.3390/cancers15030608

AMA Style

Steiner N, Göbel G, Mauser L, Mühlnikel L, Fischinger M, Künz T, Willenbacher W, Hetzenauer G, Rudzki J, Nussbaumer W, et al. Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study. Cancers. 2023; 15(3):608. https://doi.org/10.3390/cancers15030608

Chicago/Turabian Style

Steiner, Normann, Georg Göbel, Leonie Mauser, Lena Mühlnikel, Marie Fischinger, Tina Künz, Wolfgang Willenbacher, Gabriele Hetzenauer, Jakob Rudzki, Walter Nussbaumer, and et al. 2023. "Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study" Cancers 15, no. 3: 608. https://doi.org/10.3390/cancers15030608

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop