Sufficient and Timely Autologous Stem Cell Harvest After Chemoimmunotherapy with Alemtuzumab In Combination with Bi-Weekly CHOP as First Line Treatment In Systemic Peripheral T-Cell Lymphomas (PTCL): a Feasibility Analysis From the First Randomized Trial In Systemic PTCL (ACT trial)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2395-2395
Author(s):  
Francesco d'Amore ◽  
Maria Gomes da Silva ◽  
Sirpa Leppa ◽  
Antonio Pezzutto ◽  
Thomas Relander ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
First Line ◽  
Cd34 Cells ◽  
Cell Harvest ◽  
First Line Treatment

Abstract Abstract 2395 While already tested in T-PLL, the impact of chemo-immunotherapy with alemtuzumab in combination with bi-weekly CHOP on autologous stem cell harvest (ASCH) has not yet been analysed in the context of first line treatment of primary systemic peripheral T-cell lymphoma (PTCL). We therefore evaluated the feasibility of ASCH in the first 23 patients of the ongoing international multicenter ACT-1 study, the first, and so far only, randomized trial in primary systemic PTCL. The ACT trials (ACT-1 + ACT-2) test the addition of alemtuzumab to CHOP followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT+ASCT). The aims of the analysis were: (i) feasibility of ASCH in alemtuzumab + CHOP (A-CHOP) treated patients as compared to patients not receiving the antibody, but otherwise treated and managed in the same way, and (ii) comparison of ASCH counts in the two treatment arms. By July 2010, 20 patients, 11 in the standard treatment (arm A) and 9 in the experimental treatment (arm B) cohort, had undergone induction therapy and had been primed for subsequent ASCH according to local guidelines. Histological subtype distribution in the two treatment groups showed: PTCL not otherwise specified N=4 (arm A) and N=5 (arm B), angioimmunoblastic N=5 (arm A) and N=4 (arm B), extranodal NK/T-cell, nasal type N=1 (arm A), hepatosplenic N=1 (arm A). Pre-therapeutic evidence of bone marrow involvement was present in 4 (arm A) and 2 (arm B) patients, respectively. Of the original 23 patients, three did not undergo stem-cell harvest due to progressive disease (1 pt), patient's decision (1 pt), and pre-therapeutic CNS involvement (1 pt). Among the 20 harvested patients, ASCH failure was experienced in three patients (standard arm N=1 and experimental arm N=2; p=0.57). In two patients (one in each treatment cohort) a suboptimal stem cell yield could be optimized by the use of plerixafor according to local guidelines. A comparison of stem cell counts (CD34+ cells × 106/kg body weight) from the two treatment cohorts showed a trend towards moderately lower stem cell yields in alemtuzumab-treated patients (3.34 CD34+ cells × 106/kg body weight in arm B vs 6.54 CD34+ cells × 106/kg body weight in arm A, p=0.03). In conclusion, the addition of alemtuzumab to bi-weekly CHOP in the setting of first-line therapy of primary systemic PTCL does not significantly impair ASCH prior to upfront autologous stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Results of Cytarabine-Containing Induction Followed By Consolidation with Autologous Stem Cell Transplant and Rituximab Maintenance As Primary Treatment for Mantle Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1995-1995
Author(s):  
Umberto Falcone ◽  
Shaheena Bashir ◽  
Khalil Al-Farsi ◽  
Laurie Watkins ◽  
C. Denise Turvey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
First Line ◽  
Rituximab Maintenance ◽  
Cd34 Cells ◽  
Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) often follows an aggressive course and remains incurable with standard therapies. First-line chemotherapy followed by consolidation with high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) has become a standard of care in eligible patients (pts). As relapse remains the main cause of treatment failure, strategies such as intensifying induction therapy with high-dose cytarabine or adding rituximab maintenance (RM) have been tested to reduce the relapse rate (RR) post-ASCT. We evaluated the effect of the addition of cytarabine and RM on the outcome of pts undergoing ASCT. Methods: We conducted a retrospective analysis of consecutive MCL pts who underwent ASCT after first-line chemotherapy at the Princess Margaret Cancer Centre between 2000-2013. Pts received induction with CHOP, RCHOP, or RCHOP alternating with RDHAP (RCHOP/RDHAP), followed by HDT with or without total body irradiation (TBI). All pts had a documented response to induction using Cheson 1999 criteria. After ASCT, pts received maintenance with single-agent rituximab 375 mg/m2 or were simply observed. Results: 98 MCL pts were treated: median age was 56 years (36-66), 15 pts (15%) had blastoid or pleomorphic subtype, 85 pts (87%) had stage IV disease. MIPI was high risk in 18 pts (19%). Induction therapy: CHOP 14 pts (14%), RCHOP 57 (58%), and RCHOP/RDHAP 27 (28%). After induction CR was obtained in 44%, PR in 56% pts. CR rates were: CHOP 7 (50%), RCHOP 25 (44%), RCHOP/RDHAP 12 (44%) (P=ns). 89% pts had collected > 5*106 CD34/kg after RCHOP, and 78% after RCHOP/RDHAP (P=ns). Overall 66/98 pts (67%) had > 5*106 CD34/kg collected with 1 apheresis (Table 1). HDT was melphalan+etoposide for 63% pts, cytarabine+melphalan for 31% pts; 77 (79%) also received TBI. Median time from diagnosis to ASCT was 7.5 months (2.5, 33.4). Post-ASCT responses: CR 92 pts (94%), PR 4 (4%), 2 (2%) PD. Median time to ANC ≥0.5 were 10 days (CHOP), 11 days (RCHOP), and 11 days (RCHOP/RDHAP), while median days to PLT≥20 were 9 (CHOP), 11.5 (RCHOP), and 13 (RCHOP/RDHAP). Post-ASCT, 31% of pts had normal blood counts at 3 months which improved to 52% at 1 year post-ASCT. Maintenance data were available for 95/98 pts. RM was given to 72 pts (74%). Median follow-up from date of transplant for the entire cohort was 3.22 years (range 0.7 - 14.1). The 2-year and 5-year PFS were 85.8% (76.7-91.5) and 52.2% (37.7-64.7), respectively. 32 pts relapsed after ASCT (32.65%). Relapse occurred in 3 (11%) pts after RCHOP/RDHAP, 19 (33%) after RCHOP, and 10 (71%) after CHOP. Median time to relapse was 9 years (95%CI: 4.7-NR). 2-year and 5-year RR were 14.54% and 41.65%, respectively. Median OS was 9.15 years (95%CI: 7.3-NR), 2-year OS was 88.8% (80.2-93.8), and 5-year OS was 74.9% (61.7-84.2%). For patients observed without treatment post-ASCT, median PFS was 2.87 years (1.22-4.63) and median OS 5.19 years (1.66-NR), while for those receiving RM, PFS was 9.06 years (4.97-NR, p<0.001) and median OS has not yet been reached (7.30- NR, p=0.009). Conclusions: Response rate and PFS were similar between different induction regimens. The outcomes of responding pts following ASCT appear superior to previous strategies. Our patients enjoyed a very long PFS and median OS is surprisingly long as well. Within the limits of a retrospective study, our data support the use of rituximab maintenance, showing a significant benefit in both PFS and OS. Table 1. ASCT data Stem cell collection CHOP RCHOP RCHOP/RDHAP P value Pts collecting > 2x106 /Kg CD34+ cells in 1 day 4/14 (29%) 44/57 (77%) 17/27 (67%) 0.002 Pts collecting 2-5 x106 /Kg CD34+ cells N/A 6/57 (11%) 6/27 (22%) Pts collecting >5 x106 /Kg CD34+ cells N/A 51/57 (89%) 21/27 (78%) 0.153 Engraftment median (range) Days to ANC ≥ 0.5 10 (9,11) 11 (9, 12) 11 (9, 12) Pts with ANC ≥ 0.5 ≤ 11 days 13/13 (100%) 45/52 (87%) 21/25 (84%) 0.33 Days to PLT ≥ 20 9 (7, 15) 11.5 (9, 17) 13 (9, 26) Pts with PLT ≥ 20 ≤ 12 days 12/13 (92%) 37/52 (71%) 8/25 (32%) 0.0001* Days from ASCT to discharge 13 (11,26) 14 (11,30) 13 (11,23) PTs requiring RBC Transfusions 11 (79%) 43 (75%) 22 (81%) 0.821 Number of RBC Transfusions 2 (0, 4) 2 (0, 7) 3(0, 6) Pts requiring PLT Transfusions 12 (86%) 52 (93%) 25 (93%) 0.759 Number of PLT Transfusions 1 (0, 4) 2 (1, 9) 3 (1, 5) * comparison CHOP Vs R-CHOP: not significant, p=0.113 Legend. ASCT: autologous stem cell transplant; Pts: patients; ANC: absolute neutrophils count; PLTs: platelets; RBC: red blood cells. Disclosures Kuruvilla: Hoffmann LaRoche: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Gilead: Consultancy; Janssen: Consultancy, Honoraria; Merck: Honoraria; Bristol-Myers Squibb: Honoraria; Lundbeck: Honoraria; Karyopharm: Honoraria.

Effectiveness and tolerability of first-line autologous stem cell transplant and maintenance rituximab for mantle cell lymphoma

2017 ◽  
Vol 53 (3) ◽  
pp. 347-351
Author(s):  
Umberto Falcone ◽  
Haiyan Jiang ◽  
Shaheena Bashir ◽  
Richard Tsang ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
First Line ◽  
Mantle Cell

Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2689-2689
Author(s):  
Sarah J. Nagle ◽  
Kaitlin Woo ◽  
Rosemarie Mick ◽  
Stephen J. Schuster ◽  
Sunita D. Nasta ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Historical Controls ◽  
First Line Treatment

Abstract Abstract 2689 Salvage chemotherapy and autologous stem cell transplant (ASCT) remain the current standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who have primary refractory disease or relapse after initial therapy. The addition of rituximab results in improved overall survival (OS) after first line treatment, but cure rates of salvage therapy and ASCT are inferior when compared to historical controls (Gisselbrecht et al, JCO 2010). In the pre-rituximab era, patients with DLBCL who progressed after ASCT had an extremely poor prognosis, with a median OS of 3 months from the time of progression (Vose et al, Blood 1992). There is a paucity of data regarding outcomes and clinical patterns following progression after ASCT in the rituximab era. We conducted a retrospective analysis using our institutional database of DLBCL patients who underwent ASCT for primary refractory or relapsed disease. For those who progressed after ASCT, we evaluated OS defined as time from date of progression after ASCT to date of death from any cause or last follow-up. We also analyzed OS for various subgroups based on their clinical characteristics and post-progression therapy. The impact of post-progression therapy on outcome was assessed by calculating OS from the time of exposure to a particular treatment to date of death from any cause or last follow-up. Median OS was estimated by the Kaplan-Meier method and subgroup comparisons were performed using the log rank test. We identified 215 patients with primary refractory or relapsed DLBCL who underwent ASCT between January 1, 2005 and December 31, 2011. All patients received rituximab as part of their first line treatment. Fifty-six patients (26% of total) were found to have progression after ASCT. Eight patients were excluded from the analysis because they were not re-biopsied at relapse (n=5) or they had indolent disease at relapse (n=3). Data on the remaining 48 patients (median age 57 years; range 20–74) were further analyzed. The median OS from progression after ASCT for the entire cohort was 10.7 months (95% CI: 6.8–18.0 months). Patients who progressed < 1 year from ASCT (n=39) had a significantly shorter OS than those who progressed ≥ 1 year from ASCT (n=9): 9.5 vs. 26.7 months (p=0.02). Patients with at least stable disease as first assessment after ASCT (n=29) had a significantly longer OS than those who progressed immediately after ASCT (n=19): 18 vs. 6 months (p=0.01). Patients who were exposed to at least one novel agent (lenalidomide, radioimmunotherapy, non-rituximab monoclonal antibodies or tyrosine kinase inhibitors) as part of their post-progression therapy after ASCT (n=20) had a median OS of 11.2 months from treatment initiation. In contrast, patients who were treated with conventional cytotoxic chemotherapy but not novel agents (n=20) had a median OS of 6.7 months. In particular, patients who underwent radioimmunotherapy at some point after progression post-ASCT (n=9) had a median OS of 17.5 months (95% CI: 2.6-n/a months) with one patient in complete response > 48 months after the treatment. Patients who underwent allogeneic stem cell transplant following progression after ASCT (n=6) had a median OS of only 7.1 months (95% CI: 0.8-n/a months). In the rituximab era, the median OS of DLBCL patients who progress after ASCT appears improved when compared to historical controls, especially in those who progress > 1 year from ASCT. Patients with DLBCL progressing after ASCT should be considered for therapy with novel agents, which may result in long term survival. Disclosures: No relevant conflicts of interest to declare.

Secondary neutropenia (SN) after autologous hematopoietic stem cell transplantation (AHSCT) in patients (pts) with lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6552-6552
Author(s):  
Sunita Nathan ◽  
John Joseph Maciejewski ◽  
Elizabeth Shima Rich ◽  
Parameswaran Venugopal ◽  
Kent W. Christopherson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Cd34 Cells ◽  
Transplant Complications

6552 Background: Plerixafor for mobilization of autologous stem cells (ASC) has increased the yield of transplanted ASC and is evolving as an important option for mobilization. A prior study reported a 10% incidence of SN after AHSCT (BMT 2009 Aug; 44(3): 175-83). Incidence and outcome of SN in the setting of Plerixafor/G-CSF (P/G), is unknown. We report the incidence and possible etiology for the development of SN in pts undergoing AHSCT for lymphoma at our institution. Methods: Data from 80 consecutive AHSCT pts over a 2 year period were reviewed. All pts were mobilized using P/G. Demographics, AHSCT indication, prior therapies (Rx), conditioning regimen (CR), engraftment and post-transplant complications were identified and collected. SN was defined as ANC <1000 after initial engraftment. Results: 80 pts underwent an AHSCT for lymphoma from 2009-11. 70 pts had evaluable data. 37 (52.86%) pts (average age 55.4 yrs) were male and 33 (47.14%) pts (average age 48.3 yrs) female. 25 (35.7%) pts had ≥2 comorbidities. Indications included relapsed/ refractory B-NHL, T-NHL and HL. 47 (67%) pts had Stage IV ds, 48.9% with BM involvement. 17 (24.3%) pts had >2 Rx, 18 (25.7%) with loco-regional XRT and 3 (4.3%) with RIT. CR included BEAM, BEC and Benda-EAM +/- Rituxan. # of CD34+ cells given ranged; 1.77-19.99 x 10^6/kg. Neutrophil engraftment occurred at a median of 11 days. 26 (37.14%) pts developed SN possibly from PCP prophylactic antibiotics and infections. Prior BM involvement, Rx or XRT had no role. 5 (45.4%) pts with Benda-EAM CR had SN. Associated morbidity/mortality were not noted. Conclusions: We conclude that secondary neutropenia is common after autologous stem cell transplant using the Plerixafor/GCSF combination for mobilization and is higher than reported in the literature (37% vs 10%). Patients who received this combination for mobilization should be followed up closely in the post-transplant period for secondary neutropenia. About half the patients who received the Benda-EAM conditioning regimen developed secondary neutropenia warranting its use with caution outside of a clinical trial.

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