Autologous Stem Cell Transplantation Is Feasible and of Potential Benefit In Very Elderly Patients with Lymphoma and Limited Comorbidities

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3561-3561
Author(s):  
Rebecca Elstrom ◽  
Peter Martin ◽  
Tsiporah B. Shore ◽  
Richard R. Furman ◽  
Jia Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Clinical Research ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Medium Risk ◽  
One Year

Abstract Abstract 3561 Introduction: In patients with Hodgkin lymphoma (HL) and non-Hodgkin's lymphoma (NHL) for whom initial therapy is not curative, high dose chemotherapy followed by autologous stem cell transplantation (AutoSCT) may offer a second chance for cure or long term remission. Because of the potential toxicities of this therapy, elderly patients are usually not considered candidates for this approach. Although recent publications have suggested that AutoSCT may benefit some patients over 65 years of age, data regarding feasibility in older patients (69 or greater) are lacking. Patients and Methods: The stem cell transplant database at Weill Cornell Medical College was reviewed to identify patients with a diagnosis of lymphoma (HL or NHL) age 69 or greater who had undergone AutoSCT. Patients were included if age, date of transplant, response and survival data were available. Baseline Charlson comorbidity risk index (CCI) was calculated and correlated with outcome. Results: Twenty-one patients aged 69 or greater (range 69–86, median 71) with adequate records were identified who underwent autologous stem cell transplantation for treatment of lymphoma. Thirteen patients had diffuse large B cell lymphoma, 3 had transformed indolent lymphoma, 2 had Burkitt lymphoma, one had peripheral T cell lymphoma, one had follicular lymphoma, and one had HL. Sixteen patients underwent AutoSCT in first relapse with chemotherapy sensitive disease, 2 patients had primary refractory lymphoma, 2 were in 2nd or greater relapse, and one patient was in first complete remission (CR). Two patients underwent total body irradiation (TBI) as part of conditioning, while the other 19 patients underwent conditioning with chemotherapy alone. Sixteen patients (76%) achieved CR following autoSCT, while 3 patients did not achieve CR; 2 patients died before response assessment could be undertaken. With median follow up of 20 months, the median progression-free survival following autoSCT was 10 months and median overall survival was 18 months. Age was associated with PFS (HR 1.18, p=0.05, 95% C.I. 1.05–1.33) but not OS (HR 1.11, p=0.09, 95% C.I. 0.98–1.25). Eight of 18 patients with adequate follow up (44%) remained in remission for at least 18 months post-transplant. CCI data were available for 19 patients. Four patients (19%) died within or shortly after 100 days, all of transplant-related toxicity. Two of these 4 patients were high risk by CCI, one was medium risk, and CCI data were not available for the fourth patient. Three other patients were of medium risk; 2 are alive in CR and one died of progressive lymphoma 19 months after transplantation. Thirteen patients were of low risk by CCI. Of these patients, 9 (69%) are either alive at time of follow up or survived for greater than one year after transplant, while 4 (31%) died within one year of progressive lymphoma. Conclusion: Autologous stem cell transplantation is feasible and of potential benefit in selected elderly patients with lymphoma. Age alone need not exclude patients with good functional status and limited comorbidity from this therapeutic approach. Consideration of comorbidities may allow selection of patients most likely to tolerate and benefit from AutoSCT. Disclosures: Furman: GlaxoSmithKline: Clinical research funding, Consultancy, Research Funding, Speakers Bureau; Genentech: Clinical Research Funding, Consultancy, Research Funding, Speakers Bureau; Cephalon: Speakers Bureau, Speakers bureau; Calistoga: Consultancy, Honoraria; Celgene: Clinical Research, Consultancy, Research Funding. Leonard:Hospira: Consultancy, Honoraria; Cell Therapeutics: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Biogen IDEC: Consultancy, Honoraria; Calistoga: Consultancy, Honoraria; Johnson and Johnson: Consultancy, Honoraria; EMD Serono: Consultancy, Honoraria; Sanofi Aventis: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Biotest: Consultancy, Honoraria; Cephalon: Consultancy, Honoraria; Pharmion: Consultancy, Honoraria; Eisai: Consultancy, Honoraria; Cougar Biotechnology: Consultancy, Honoraria; Immunomedics: Honoraria; Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

scholarly journals Upfront Autologous Stem Cell Transplantation for Newly Diagnosed Elderly Multiple Myeloma (MM) Patients: A Prospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1989-1989
Author(s):  
Laurent Garderet ◽  
Cyrille Touzeau ◽  
Anne-Marie Stoppa ◽  
Denis Caillot ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged <65 years. However, at the era of novel induction regimens, and because of better patient selection and supportive care, ASCT may prove to be a valid treatment option even in older MM patients. Therefore, some investigators are questioning the widely used 65 years age limit. Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

scholarly journals Loss of quiescence and impaired function of CD34+/CD38low cells one year following autologous stem cell transplantation

Haematologica ◽  
2013 ◽  
Vol 98 (12) ◽  
pp. 1964-1971 ◽  
Author(s):  
C. M. Woolthuis ◽  
A. Z. Brouwers-Vos ◽  
G. Huls ◽  
J. T. M. de Wolf ◽  
J. J. Schuringa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Impaired Function ◽  
One Year

Benefit of the Adjunction of Rituximab in Salvage Regimen before Autologous Stem-Cell Transplantation (ASCT) in Follicular Lymphoma at Relapse. A Single Institution Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2075-2075 ◽  
Author(s):  
Karim Belhadj ◽  
Yosr Hicheri ◽  
Cécile Pautas ◽  
Taoufik El Gnaoui ◽  
François Hémery ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Treated Group ◽  
Initial Diagnosis ◽  
High Dose ◽  
Salvage Regimen ◽  
Allogenic Transplantation

Abstract Follicular lymphomas have an indolent evolution with a median survival ranging between 8–10 years. At relapse, high-dose therapy followed by autologous stem-cell transplantation (ASCT) can be considered as an alternative to conventional chemotherapy. However, efficacy of this strategy remains controversial. The purpose of our retrospective study is to evaluate ASCT in the pre and post rituximab era as consolidation after 2nd or 3rd remission (at least PR). Between March 1989 and Apr 2004, 54 pts were treated at relapse with ASCT in our institution. At initial diagnosis, median age was 47 yrs (range 24–61) and FLIPI score was ≥ 3 in 18%. ASCT was performed in 2nd remission in 43 cases and in 3rd remission in 11 [median delay diagnosis-ASCT=44 months (range 7–139) and 53 months (range 21–227), respectively]. The conditioning regimens used were: VP16/cyclophosphamide/TBI in 33 cases, cyclophosphamide/TBI in 9, BEAM in 10 and cyclophosphamide/busulfan in 2. After ASCT, 49 pts achieved CR, 4 achieved PR and one pt progressed. In Dec 2004, with a median follow-up of 4.7 yrs, 27 pts (50%) had relapsed after ASCT with a median time to relapse of 12 months (range 2–95) and 18 pts have died. Causes of death were: lymphoma recurrence in 8 cases, secondary malignancy in 6 cases (3 MDS/AML, 2 radiation-associated solid tumors, 1 EBV associated lymphoma after a new salvage treatment including allogenic transplantation), and late infection in 4 cases, 2 of them occurring in remission (varicella and septicaemia) and 2 others after a new salvage therapy (cellulitis during chemotherapy-induced neutropenia and HHV6 encephalitis after allogenic transplantation). Ten-year overall survival (OS) from initial diagnosis was 68%. Five-year OS and event-free survival after ASCT were 74 and 52%, respectively. Patients treated at relapse before 1998 did not receive rituximab (rituximab-naive pts: n=29) and those treated after 1998 received a rituximab-based salvage regimen before ASCT (rituximab-treated pts: n=25). The main characteristics of the two populations were as indicated in the table below: rituximab-naive group rituximab-treated group N 29 25 FLIPI at initial diagnosis (Low/Intermediate/High) % 41/48/11 27/46/27 Median age at ASCT (yrs) 50 (range35–60) 52 (range 30–62) ASCT performed in 2nd remission 23 20 ASCT performed in 3rd remission 6 5 Median duration of response following last treatment line prior to ASCT (months) 21 (range 1–91) 11 (range1–49) After adjusting for the follow-up (median follow-up of the rituximab-treated group: 3.8 yrs), comparison between the two groups of pts treated with ASCT at relapse shows a significantly better OS of the rituximab-treated group as compared to that of the rituximab-naïve group (100 vs 61% at 4 years, p=0.01). These data suggest that the well-established efficacy of rituximab in FL is not abrogated by consolidative ASCT delivered at relapse in pts not previously treated with rituximab and further emphasize the superiority of immunochemotherapy over chemotherapy alone.

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