Impact Of Autologous Stem Cell Transplantation In Older Patients With Mantle Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3384-3384
Author(s):  
Zachary Frosch ◽  
Marlise R. Luskin ◽  
Daniel J. Landsburg ◽  
Stephen J. Schuster ◽  
Jakub Svoboda ◽  
...  

Abstract Background Mantle cell lymphoma (MCL) is a disease of older adults with median age at diagnosis of over 60. While receipt of high-dose chemotherapy with autologous stem cell transplant (ASCT) consolidation has been shown to improve progression free survival (PFS) following standard induction chemo-immunotherapy in younger patients, the benefit of ASCT consolidation in older patients remains uncertain. To address this, we evaluated the benefit of ASCT in a cohort of older patients with MCL treated at our center. Methods Patients age over 60 diagnosed with MCL and treated at the University of Pennsylvania between January 2003 and June 2012 treated with R-CHOP or R-HyperCVAD induction and deemed fit for ASCT at the completion of induction were analyzed. Induction regimen was chosen based on treating physician and/or patient preference. PFS was defined as time from initiation of therapy to radiographic or biopsy proven progression or death in remission, and overall survival (OS) was defined as time from diagnosis to death from any cause. Response assessments were performed at the discretion of the treating physician. Results Thirty-eight patients were identified: 20 (53%) received R-CHOP induction and 18 (47%) received R-HyperCVAD. Baseline patient and disease-related characteristics were similar between groups (Table 1). With R-CHOP, patients received a median of 6 cycles of chemotherapy including mobilization (range 6 to 8). With R-HCVAD, patients received a median of 8 (A or B) cycles including mobilization (range 5 to 8). Adverse events requiring hospitalization or a change in dose or timing of therapy occurred in 67% of R-CHOP and 84% of R-HyperCVAD patients (p=0.27). The most common adverse event was neutropenic fever/infection (15 patients). Significantly more patients undergoing R-HyperCVAD induction required red cell or platelet support (17 [100%] vs 9 [64%], p=0.012). Thirteen patients (72%) completed all cycles of R-HyperCVAD. Three patients (16%) were converted to R-CHOP because of toxicity. Patients who completed at least cycle 2B were included in the R-HyperCVAD group for analysis. Complete response was achieved in all but one patient in each induction group. After R-CHOP induction, 15 (75%) patients underwent ASCT. After R-HyperCVAD, 6 (33%) patients underwent ASCT. The most common reasons for not undergoing ASCT were physician recommendation (6 patients, 35%) and patient preference (5, 29%). Rates of adverse events were similar during ASCT after R-CHOP (9, 60%) or R-HyperCVAD (3, 50%). There was no ASCT associated mortality. Among those not transplanted, after R-HyperCVAD 6 (50%) received rituximab maintenance and none did after R-CHOP. With a median length of follow-up of 2.7 years, median PFS was 2.6 years and median OS was 6.0 years. Kaplan-Meier plots for PFS are shown in Figure 1. Patients treated with R-CHOP+ASCT and R-HyperCVAD alone both had longer PFS than patients treated with R-CHOP alone (median PFS 3.2 vs 1.6 years, p=0.019 and 4.0 vs 1.6 years, p=0.009 respectively). Patients undergoing R-CHOP + ASCT had similar PFS compared to R-HyperCVAD alone (p=0.525). No significant differences in OS survival were found (Figure 2). Conclusion Among patients age over 60 eligible for ASCT in primary MCL, ASCT prolonged PFS after R-CHOP induction and resulted in similar PFS to that seen with R-HyperCVAD. Our results suggest that fit older patients with MCL benefit from chemotherapy with either R-CHOP+ASCT or R-HyperCVAD, and that the former regimen may be preferable due to lower rates of toxicity and need for transfusion support. These findings should be confirmed prospectively. Disclosures: No relevant conflicts of interest to declare.

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


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

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.


2017 ◽  
Vol 23 (3) ◽  
pp. S265-S266
Author(s):  
Irl Brian Greenwell ◽  
Kelly Valla ◽  
Sarah Caulfield ◽  
Jeffrey M. Switchenko ◽  
Ashley Staton ◽  
...  

2017 ◽  
Vol 53 (3) ◽  
pp. 347-351
Author(s):  
Umberto Falcone ◽  
Haiyan Jiang ◽  
Shaheena Bashir ◽  
Richard Tsang ◽  
Vishal Kukreti ◽  
...  

1998 ◽  
Vol 16 (12) ◽  
pp. 3803-3809 ◽  
Author(s):  
I F Khouri ◽  
J Romaguera ◽  
H Kantarjian ◽  
J L Palmer ◽  
W C Pugh ◽  
...  

PURPOSE Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.


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