Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study

2019 ◽  
Vol 37 (10) ◽  
pp. 823-833 ◽  
Author(s):  
Caroline Houillier ◽  
Luc Taillandier ◽  
Sylvain Dureau ◽  
Thierry Lamy ◽  
Mouna Laadhari ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
Intensive Chemotherapy ◽  
Free Survival

PURPOSE To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m2 day (D) 1, methotrexate 3 g/m2 D1; D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m2 D1, cytarabine 3 g/m2 D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m2/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2). WBRT delivered 40 Gy (2 Gy/fraction). The primary end point was 2-year progression-free survival. Cognitive outcome was the main secondary end point. Analysis was intention to treat in a noncomparative phase II trial. RESULTS Between October 2008 and February 2014, 140 patients were recruited from 23 French centers. Both WBRT and ASCT met the predetermined threshold (among the first 38 patients in each group, at least 24 patients were alive and disease free at 2 years). The 2-year progression-free survival rates were 63% (95% CI, 49% to 81%) and 87% (95% CI, 77% to 98%) in the WBRT and ASCT arms, respectively. Toxicity deaths were recorded in one and five patients after WBRT and ASCT, respectively. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. CONCLUSION WBRT and ASCT are effective consolidation treatments for patients with PCNSL who are 60 years of age and younger. The efficacy end points tended to favor the ASCT arm. The specific risk of each procedure should be considered.

High-Dose Chemotherapy With Autologous Stem-Cell Transplantation and Hyperfractionated Radiotherapy As First-Line Treatment of Primary CNS Lymphoma

2006 ◽  
Vol 24 (24) ◽  
pp. 3865-3870 ◽  
Author(s):  
Gerald Illerhaus ◽  
Reinhard Marks ◽  
Gabriele Ihorst ◽  
Roland Guttenberger ◽  
Christoph Ostertag ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Clinical Improvement ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Purpose To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. Patients and Methods Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. Results Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). Conclusion Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

scholarly journals Primary CNS Lymphoma—Radiation-Free Salvage Therapy by Second Autologous Stem Cell Transplantation

2011 ◽  
Vol 17 (2) ◽  
pp. 281-283 ◽  
Author(s):  
Benjamin Kasenda ◽  
Elisabeth Schorb ◽  
Kristina Fritsch ◽  
Claudia Hader ◽  
Jürgen Finke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma

Plasmablastic Morphology Is an Independent Predictor of Poor Survival After Autologous Stem-Cell Transplantation for Multiple Myeloma

1999 ◽  
Vol 17 (5) ◽  
pp. 1551-1551 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Rafael Fonseca ◽  
Martha Q. Lacy ◽  
Thomas E. Witzig ◽  
Terry M. Therneau ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Survival Time ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Independent Predictor ◽  
Progression Free Survival ◽  
Poor Survival ◽  
Free Survival

PURPOSE: To study the prognostic value of plasmablastic morphology after autologous stem-cell transplantation for relapsed or primary refractory myeloma. PATIENTS AND METHODS: Seventy-five patients were studied. Investigators blinded to the clinical details of the individual cases reviewed bone marrow aspirate slides to determine plasmablastic classification. Plasmablasts were defined using strict, well-described criteria. Plasmablastic morphology was considered to be present (plasmablastic myeloma) when 2% or more plasmablasts were present in the plasma-cell population. RESULTS: Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Twenty-eight percent of patients had plasmablastic morphology. A significantly greater proportion of patients with plasmablastic morphology had abnormal cytogenetics compared with those with nonplasmablastic classification (73% v 31%, respectively; P = .003). The overall survival rate measured from the time of transplantation was significantly worse in patients with plasmablastic morphology compared with those without (median survival time, 5 months v 24 months, respectively; P < .001). Progression-free survival time was shortened also, with a median time of 4 months compared with 12 months, respectively (P < .001). In the multivariate analysis, plasmablastic classification was the most powerful prognostic factor after transplantation for both overall (P = .001) and progression-free survival rates (P < .001). We also identified three risk groups based on plasmablastic morphology: plasma-cell labeling index, lactate dehydrogenase, and cytogenetics. The median overall survival time was 38 months when none of these factors was abnormal, 17 months with one abnormal factor, and 8 months with two or more abnormal factors (P < .001). CONCLUSION: Plasmablastic morphology is a powerful independent predictor of poor survival rate after autologous stem-cell transplantation for relapsed or primary refractory myeloma.

scholarly journals Comparison of the Low Toxicity Tecam Conditioning Regimen to BEAM in Patients with Lymphoma Requiring Autologous Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3188-3188 ◽  
Author(s):  
Dana Rosenberg ◽  
Erel Joffe ◽  
Uri Rozovski ◽  
Chava Perry ◽  
Ilya Kirgner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Low Toxicity ◽  
Length Of Hospitalization ◽  
Dose Reductions

Abstract Introduction: Autologous Stem Cell Transplantation (ASCT) has become the cornerstone of managing relapsed lymphomas. However, its use in elderly patients or those with comorbidities is limited because of high regimen related toxicities (RRT). Several chemotherapy regimens have been suggested to minimize RRT while maintaining the antitumor effect. TECAM (Thiotepa 160 mg/m2 over 4 days , Etoposide and Cytarabine 800mg/m2 over 4 days, Cytoxan 60 mg/kg, and Melphalan 120 mg/m2 over 2 days) is a reduced toxicity modification for the commonly used BEAM protocol. Aim: This study aimed to compare the safety and efficacy or the TECAM regimen with that of its more intense BEAM counterpart. Methods: A retrospective cohort study of all patients who underwent ASCT for treatment of lymphoma with either BEAM or TECAM conditioning regimens at the Tel Aviv Medical Center between October 1999 and January 2014. We compared early (≤100 days) mortality, RRT rate, time to engraftment and length of hospitalization as well as overall and progression free survival. Results: A total of 146 patients (76 BEAM, 70 TECAM) were included in the analysis. Median follow up was 47 months. Patient treated with TECAM were older (54.5 vs. 45.5, p=0.001), and nearly 20% (n=13) of them had dose reductions (average 17±7%), as opposed to a single patient in the BEAM arm. Conversely, TECAM patients had a longer time interval from first diagnosis to transplant (22 vs. 13 months, p<0.001), and had a higher rate of CR at transplantation, though not statistically significant (57% vs. 49%, p=0.39). At 100 days there was no difference in mortality rates between the groups (5 vs. 7 deaths, TECAM vs. BEAM, p=0.63). There was no difference in the median time to engraftment of neutrophils (11 days) or platelets (13 days), nor in the median length of hospitalization (25 days TECAM vs. 24 days BEAM, p=0.28). Similarly, there was no difference in the transfusion requirements, rate of severe mucositis, bacteremia or ARDS. There was no statistically significant difference in PFS (26 months vs. not reached, TECAM vs. BEAM, p=0.16), nor in OS (not reached for both, p=0.55). In multivariable analysis the only factor associated with PFS was not entering transplantation in CR (HR 2.4, 95% CI 1.4-4.0, p=0.001). Similarly, factors associated with OS were older age (HR 1.023, 95% CI 1.004-1.043 per year, p=0.016) and non-CR at transplantation (HR 2.4, 95% CI 1.4-4.4, p=0.003). Discussion: We found comparable results for BEAM and its low toxicity counterpart TECAM. There were no differences in early mortality, RRT, time to engraftment, PFS, or OS. This was despite the fact that patients treated with TECAM were, on average, nine years older, and probably perceived to be frailer as indicated by a considerably higher rate of dose reductions. This study has several limitations that extend beyond its retrospective single institution nature. It encompasses a heterogeneous group of lymphomas, and there was possibly a selection bias allocating patients with a more severe disease to BAEM. Regardless, it suggests that TECAM could provide a lower toxicity alternative for ASCT conditioning in a selected group of patients. Table 1. Baseline characteristics BEAM (n=76) TECAM (n=70) p vlaue Age* 45.5 [29.5-54.0] 54.5 [41.3-65.0] 0.001 Sex (female) 31 (40.8%) 32 (45.7%) 0.67 Lymphoma type 0.09 Diffuse large B cell 32 (42.1%) 35 (50.7%) Hodgkin's 15 (19.7%) 15 (21.7%) T Cell 16 (21.1%) 4 (5.80%) Follicular 3 (3.95%) 6 (8.70%) Mantle cell 7 (9.21%) 8 (11.6%) Other 3 (3.95%) 1 (1.45%) Months from diagnosis* 13 [9-22] 22 [12-37] <0.001 Comorbidity index 1.5 [0-2] 1.0 [0-2] 0.58 CR at transplantation 37 (48.7%) 40 (57.1%) 0.39 Dose reduction 1 (1.32%) 13 (18.6%) 0.001 CD34 < 2X106/kg: 2 (2.63%) 11 (15.7%) 0.01 *(median [IQR]) Figure 1. Overall and progression free survival Figure 1. Overall and progression free survival Disclosures Rozovski: Novartis: Other: Advisory board.

Pretransplant hemoglobin and serum creatinine levels correlate with progression free survival in myeloma patients undergoing autologous stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Taner Demirer ◽  
Guldane Cengiz Seval ◽  
Selami Kocak Toprak ◽  
Sinem Civriz Bozdag ◽  
Meltem Kurt Yuksel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
The Impact

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.

scholarly journals Tandem Autologous Stem Cell Transplantation for Multiple Myeloma Patients Based on Response to Their First Transplant—A Prospective Phase II Study

2014 ◽  
Vol 8 ◽  
pp. CMO.S16835 ◽  
Author(s):  
Michael Byrne ◽  
Donya Salmasinia ◽  
Helen Leather ◽  
Christopher R. Cogle ◽  
Amy Davis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Prospective Phase

In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) ( P = 0.0141) and percentage of marrow plasma cells before ASCT1 ( P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS.

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