scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5000-5000 ◽  
Author(s):  
Dustin E. Stevenson ◽  
James Splichal ◽  
David Ririe

Abstract Introduction: Numerous methods of stem cell mobilization for autologous donors are utilized. These strategies include the use of chemotherapy with growth factor support or growth factors alone. All strategies involve multiple injections, lab draws, and patient discomfort and inconvenience. The addition of the PEG molecule to the N-terminus of filgrastim (G-CSF) increases its serum half-life, thereby requiring less frequent dosing. Pegfilgrastim has been found to be safe and effective for patients with chemotherapy-induced neutropenia. Pegfilgrastim in healthy donors mobilizes stem cells in a dose-dependent fashion. A previous study has shown that 12mg of pegfilgrastim given after chemomobilization with cyclophosphamide mobilized sufficient stem cells for auto-grafting. In this study, we evaluated whether a single 12mg injection of pegfilgrastim could mobilize a sufficient number of CD34+ stem cells in autologous donors who did not receive chemomobilization. Methods: Six patients intending to undergo high-dose chemotherapy with stem cell transplant were enrolled onto the study. Four of the subjects had multiple myeloma and had received prior treatment. Two of these patients had previously undergone HDC/ASCT. One patient had mantle cell lymphoma and another had AL amyloidosis. All participants received a 12mg injection of pegfilgrastim. Four days after pegfilgrastim administration, a CD34 level was checked. If this level was greater than 10 cells per uL, stem cell apheresis was initiatiated. Results: Results are presented in the table below. Five of the six participants achieved a day four CD34+ level greater that 10 cells per uL and underwent successful stem cell apheresis. The one participant that failed to mobilize had been heavily pre-treated to include a prior autologous stem cell transplant. This patient underwent a repeat stem cell transplant with cells stored from a previous collection. All of the patients with multiple myeloma or amyloidosis proceeded onto high dose chemotherapy with melphalan and autologous stem cell rescue. The patient with mantle cell lymphoma received high-dose chemotherapy with cyclophosphamide, busulfan and vincristine followed autologous stem cell rescue. The most commonly reported side effect from the pegfilgrastim was bone pain. No serious side effects were noted. Conclusions: A single, 12mg injection of pegfilgrastim is capable of mobilizing sufficient numbers of stem cells in autologous donors. This regimen is convenient to both the patient and institution. Hematologic reconstitution is similar to other stem cell mobilization regimens. Alternative mobilization strategies should be considered in patients who have been heavily pretreated. Patient # Dx: Prev Tx: Day 4CD34 Count # of Apheresis sessions # of cells collected/kg Day of neutrophil recovery post transplant Day of platelet recovery post-transplant 1 MM VAD, HDC/ASCT 6.5 N/A N/A N/A N/A 2 Mantle Cell Lymphoma HyperCVAD 36.5 1 2.94 x 10(6) 10 67 3 MM VAD 47.5 2 10.36 x 10(6) 11 11 4 MM VAD 27.5 4 7.70 x 10(6) 12 15 5 MM VAD, HDC/ASCT, Thalidomide 25.0 2 3.27 x 10(6) 11 16 6 AL Amyloidosis prednisone 29.5 4 6.28 x 10(6) 11 13


2019 ◽  
Vol 26 (2) ◽  
pp. 273-278
Author(s):  
Merih K Çakar ◽  
Emre Tekgündüz ◽  
Mehmet S Dal ◽  
Alparslan Merdin ◽  
Semih Başçı ◽  
...  

IntroductionThe aim of this study was to investigate the influence of high-dose cytosine arabinoside (HDAC)-containing treatments followed by autologous hematopoietic stem cell transplantation on the survival of patients with mantle cell lymphoma.Material and methodsThe data of 27 MCL patients who were followed-up between January 2009 and December 2015 were analyzed retrospectively.ResultsThe median age of the patients was 63 (range, 45–82) with 22 (81.4%) males and 5 (18.6%) females. Eight of 27 patients were treated with HDAC-containing regimens either as induction or salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT). The patients who received HDAC-containing regimen followed by AHSCT were found to have better one-year survival compared to others ( p = 0.03). Median follow-up of patient cohort was 27.6 months and median overall survival (OS) was not reached. The probability of one-year OS for all patients was 76.8%.ConclusionOur findings suggest that HDAC treatment followed by AHSCT seems to provide the best outcome for young-fit patients presenting with mantle cell lymphoma.


2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 6668-6668
Author(s):  
E. Segota ◽  
B. Pohlman ◽  
T. Jin ◽  
E. Kuczkowski ◽  
L. Rybicki ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5828-5828
Author(s):  
Noa Lavi ◽  
Ron Ram ◽  
Odelia Amit ◽  
Netanel A Horowitz ◽  
Tzila Zuckerman

Abstract Introduction: Autologous stem cell transplantation (ASCT) is currently considered the standard first-line consolidation therapy for younger patients with mantle cell lymphoma (MCL). In general, there are limited data regarding a preferred high-dose therapy (HDT) regimen preceding ASCT to be used in patients with non-Hodgkin lymphoma (NHL). Although BEAM and BEAC regimens (including BCNU, etoposide, cytosar in both regimens and melphalan or cytoxan, respectively) have been commonly employed as conditioning HDT in patients with aggressive or recurrent NHL, there have been few reports comparing these two regimens. A retrospective analysis found the superiority of BEAM over BEAC in terms of overall survival (OS) and event-free survival (EFS). Regimen-related toxicities were similar, except that BEAM was associated with more frequent lower gastrointestinal mucositis. Other studies reported that these two regimens had equivalent efficacy and outcome, as measured by EFS and OS. Further studies are required to define the optimal regimen for each specific NHL subtype. The current study aimed to compare the efficacy and toxicity of BEAC versus BEAM as a consolidation HDT in young patients with MCL undergoing ASCT. Methods: This is a retrospective analysis of outcomes in patients with MCL who received high-dose chemotherapy with BEAM or BEAC regimen followed by ASCT in two bone marrow transplant centers in Israel. OS, progression-free-survival (PFS) and regimen toxicity were compared. Results: Fifty five patients with MCL who were diagnosed between 1995-1/2016 and received consolidation with BEAC or BEAM HDT regimen were included in the analysis. Twenty seven patients were treated with BEAM and 28 patients - with BEAC. No significant differences between the two groups were revealed in terms of age, sex, the Mantle Cell Lymphoma International Prognostic Index (MIPI), induction treatment protocol and percentage of patients who were transplanted at first complete response (CR1) (Table 1). The amount of infused CD34 cells was significantly higher in the BEAM group, and the number of days until platelet engraftment was significantly greater in the BEAC group. There were no differences in the number of blood transfusions or hospitalization days between the groups (Table 2). In terms of HDT toxicity, there was a trend to a higher rate of grade 3-4 upper mucositis with BEAM protocol; no other differences in toxicity between the regimens were observed (Table 3). Non-relapse mortality at day 30 post-transplant was 0% in both groups. A median follow-up of surviving patients was 31 (range 1-119) months. PFS at 3 years in patients receiving BEAM and BEAC was 65% and 78%, respectively (p=.75). In univariate analysis, age less than 60 years, low-to-intermediate MIPI and transplant at CR1 were found to significantly improve PFS, while no difference in PFS was found between the two treatment regimens. In multivariate analysis, low-to-intermediate MIPI and transplant at CR1 appeared to significantly increase PFS (P = 0.02 and 0.03, respectively). There was no difference in the 3-year OS between the two HDT regimens (58% in the BEAM group and 81% in the BEAC groups; p=.31). Conclusion: BEAC and BEAM high dose chemotherapy regimens followed by autologous stem cell transplantation have similar efficacy and toxicity in patients with MCL. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 864-869 ◽  
Author(s):  
Michele Magni ◽  
Massimo Di Nicola ◽  
Liliana Devizzi ◽  
Paola Matteucci ◽  
Fabrizio Lombardi ◽  
...  

Abstract Elimination of tumor cells (“purging”) from hematopoietic stem cell products is a major goal of bone marrow–supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20+ mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)–detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34+ cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls;P = .007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20+ lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.


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