Outcome in Unselected Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Following R-CHOP When Stem Cell Transplantation Is Not Feasible

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3069-3069 ◽  
Author(s):  
Roopesh R. Kansara ◽  
Kerry J. Savage ◽  
Diego Villa ◽  
Tamara Shenkier ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Research Funding ◽  
Single Agent ◽  
Refractory Disease ◽  
Cns Involvement ◽  
Entire Cohort ◽  
Multi Agent ◽  
Ecog Ps

Abstract Introduction: While R-CHOP has improved survival for DLBCL, outcome in patients (pts) with relapsed/refractory disease remains dismal and may have worsened since the introduction of immunochemotherapy. High-dose chemotherapy and stem cell transplantation (SCT) offers the best chance of secondary cure, but the majority of patients are ineligible due to age, co-morbidities or disease refractory to salvage chemotherapy. Novel agents will address this unmet medical need; however, their impact is difficult to assess without a reliable historical comparator. Herein, we evaluate the outcome in an unselected population with relapsed/refractory DLBCL following R-CHOP in whom SCT is not feasible. Methods: The BC Cancer Agency Lymphoid Cancer Database was used to identify all pts diagnosed with de novo DLBCL between Dec 2000 to Jan 2013 who were treated with curative intent R-CHOP and subsequently progressed or relapsed. Patients were excluded if they were HIV positive, had CNS involvement at diagnosis, PMBCL, composite/discordant histology or transformed lymphoma. Clinical information at baseline and at relapse/progression was compiled. Overall survival (OS) from relapse was calculated from the date of 1st relapse/progression to death or last follow-up. Progression-free survival (PFS) from relapse was defined as interval from 1st relapse/progression to the date of 2nd relapse, initiation of next line of therapy, death or last follow-up. Results: 379 pts with relapsed/refractory DLBCL were identified. 53 underwent SCT and were excluded from analysis. The remaining 326 (274 SCT-ineligible and 52 SCT-eligible pts who did not receive SCT due to toxicity or chemo-refractoriness) were analyzed. Response to primary treatment was: 44% CR; 20% PR; 2% SD; 34% PD. 174 (53%) were primary refractory (progression during or within 3 mos of primary R-CHOP). Median time from diagnosis to first recurrence was 7.8 mos (range 0 – 116). Patient characteristics at relapse: median age 70 y (range 21-93); 55% male; 59% elevated LDH; 58% ECOG PS >1; 55% stage III/IV; 18% >1 extra-nodal site; 53% IPI score at relapse > or = 3. 14 (4%) relapsed with an indolent histology only and 74 (23%) exhibited CNS involvement at relapse (54 isolated, 20 concurrent systemic). Treatment at initial relapse: 78 supportive care; 77 radiotherapy (RT) alone; 2 single agent rituximab (for indolent relapse); 168 (R)-chemo +/- RT (79 single agent, 89 multi-agent). (R)-GDP was the most commonly used multi-agent regimen (75%). 1 pt had missing information. Median follow-up for living pts from the time of first relapse was 3 y. Median OS and PFS from relapse for the entire cohort were 3.9 and 2.1 mos, respectively. Outcome was worse for pts with primary refractory disease (median OS 2.5 mos, median PFS 1.7 mos). On multivariate analysis elevated LDH, ECOG PS >1, Stage III/IV and primary refractory status were independent predictors of OS and PFS from relapse. Pts who relapsed > 2 y from diagnosis had a better median OS and PFS from relapse (11 mos and 5.7 mos, respectively). Excluding pts with CNS involvement, pts who received chemo +/- RT (median OS 6.1, median PFS 3.1 mos) or RT alone (median OS 5.7, median PFS 3.3 mos) had a marginally better outcome. Disease control was similar between pts who received multi-agent vs single agent chemotherapy (median PFS 3.3 vs 2.9 mos). Median OS and PFS from relapse for the 74 pts with CNS involvement were 3.3 mos and 2.2 mos, respectively; this was similar compared to the entire cohort. Outcome was also similar between those with isolated CNS recurrence and concurrent systemic disease but 10 pts with isolated CNS relapse survived > 2 yrs. The 14 pts with indolent histology-only relapse had a significantly better outcome (median OS 36 mos, median PFS 12 mos). Conclusion: The outcome in pts who relapse or progress following R-CHOP is exceedingly poor with standard therapy, with median OS less than 4 mos. Pts who receive treatment at initial relapse fare slightly better, but this may reflect more favorable pt characteristics. Disease control was equivalent for multi-agent vs single agent treatment. While CNS relapse is a rare event in DLBCL, a high proportion of relapsed/refractory pts have CNS disease. The presence of CNS disease did not negatively impact outcome, as outcome was dismal in the entire cohort. Novel treatments are greatly needed and these survival estimates may serve as a comparator to assess their benefit. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Savage: F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other. Villa:F Hoffmann-La Roche: Other. Shenkier:F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other. Gerrie:F Hoffmann-La Roche: Other. Klasa:F Hoffmann-La Roche: Other. Connors:F Hoffmann-La Roche: Other. Sehn:F Hoffmann-La Roche: Research funding to support BCCA Lymphoid Cancer Database Other.

Doxycycline Used As Post Transplant Antibacterial Prophylaxis Improves Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Stem Cell Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3138-3138 ◽  
Author(s):  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Suzanne R Hayman ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Antibacterial Prophylaxis ◽  
Entire Cohort ◽  
Hematological Response ◽  
Amyloid Fibril Formation ◽  
The Impact

Abstract Abstract 3138 Background: Several recent reports have suggested that doxycycline can inhibit amyloid fibril formation in different in vitro and in vivo model systems. Doxycycline is the antibiotic of choice for infectious disease prophylaxis in patients with penicillin allergy, following autologous peripheral blood stem cell transplantation for various hematological malignancies. We examined the outcome of patients with light chain amyloidosis (AL) undergoing autologous stem cell transplantation to study the impact of doxycycline used as antibacterial prophylaxis. Patients and methods: We studied 455 patients who underwent autologous stem cell transplant (ASCT) for AL between March 1996 and December 2011. We excluded 44 patients who died of transplant related complications or did not survive beyond 100 days after transplant. Patient records were reviewed to ascertain the prophylactic antibiotic used. Survival was estimated using Kaplan Meier method and the survival curves were compared using log-rank test. Cox proportional hazard model was used to estimate the prognostic impact of different variables. Results: The median age of the patients was 58 years (range, 26–74); 290 (67%) were male. The median estimated follow up for the entire cohort was 73 months (95% CI; 66, 79) and 314 (69%) were alive at last follow up. Doxycycline was used a prophylaxis in 106 (23%) of the patients, with most of the remaining receiving penicillin. The usual reason for using doxycycline was a history of penicillin allergy. Hematological response to transplant occurred in 377 (87%) patients, and there was no significant difference between patients receiving doxycycline prophylaxis compared with the rest. The median OS for the entire cohort was 161 months (95% CI; 101, NR). The median OS for those receiving doxycycline prophylaxis was not reached compared with 113 months for the rest (P=0.09). Looking specifically at those patients with a hematological response, the median OS was not reached for the doxycycline group compared with 161 months for the rest (P=0.04, figure). There was no difference in the OS between the groups among those with no hematological response. The impact of the prophylaxis was independent of the number of organs involved as well as organ response to SCT. Conclusions: The results of the current study appear to demonstrate a survival advantage for patients with AL who receives doxycycline prophylaxis, in the setting of hematological response from SCT. The results are consistent with the data regarding the effect of doxycycline on amyloid fibril formation. These initial findings should form the basis of clinical exploration of doxycycline as an adjunctive therapy in patients receiving other standard therapies for AL. Such a study can further clarify if use of doxycycline for longer duration can be of additional benefit. Disclosures: Kumar: Cephalon: Research Funding; Novartis: Research Funding; Millennium: Research Funding; Celgene: Research Funding; Merck: Consultancy, Honoraria; Genzyme: Research Funding.

Busulfan, Melphalan, and Bortezomib Compared to Single Agent High-Dose Melphalan As a Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: Long Term Follow up of a Novel Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2023-2023 ◽  
Author(s):  
Patrick Hagen ◽  
Anita D'Souza ◽  
Parameswaran Hari ◽  
Omar Davila ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase Ii ◽  
Research Funding ◽  
Single Agent ◽  
Conditioning Regimen ◽  
High Dose

Introduction: Multiple myeloma (MM) remains incurable when treated with novel myeloma therapies in combination with high dose chemotherapy and autologous stem cell transplantation (ASCT). In contrast to the accelerated development of effective new drugs for induction, maintenance, and relapse, single-agent melphalan remains the standard for conditioning before ASCT. Is this phase II trial, we prospectively evaluated a conditioning regimen consisting of high-dose intravenous busulfan and melphalan followed by bortezomib (BUMELVEL), an agent shown to be potentially synergistic in combination with alkylating agents. We report our 7 year long term follow up with direct comparison to a contemporaneous CIBMTR cohort with the primary aim of both long term progression-free (PFS) and overall survival (OS). Methods: This phase I/II study was conducted between July 2009 and May 2012 at Loyola University Medical Center. MM patients with any disease response following induction were enrolled at time of stem cell transplantation. 43 patients received BUMELVEL conditioning followed by ASCT on the phase II portion of this study. Busfulan was administered intravenously (i.v.) daily for 4 days with the first 2 days (days −6 and −5) at fixed dose of 130 mg/m2 over 3 hours and the subsequent 2 doses (days −4 and −3) adjusted to achieve a target AUC total of 20,000 μM·min determined by pharmacokinetic (PK) analysis. Melphalan at 140 mg/m2 and bortezomib at 1.6 mg/m2 were administered i.v. on days −2 and −1, respectively. Maintenance therapy was not planned. Patients received prophylaxis for oral mucositis with palifermin. Data from this phase II clinical trial were compared against a matched control cohort of contemporaneous North American MM patients from the CIBMTR database (n = 162) receiving conditioning with single agent iv melphalan at a dose of 200mg/m2. The primary objectives of this study were median PFS and toxicities. Results: Baseline patient characteristics are described in Table 1. More patients in the BUMELVEL arm received greater than one line of therapy prior to transplant (53 v 33%). There were more standard risk patients per Mayo Stratification (Kumar et al, Mayo Clin Proc 2009) in the MEL200 group (78%) v the BUMELVEL group (40%). There was no difference in response rates at day 100 (p=0.48) but a trend toward improved response at 1 year in the BUMELVEL arm with 77% achieving a VGPR or better versus 60% in the MEL200 group (p-0.09). No patients in the BUMELVEL group received planned maintenance therapy post-transplant whereas 112 (69.6%) in the MEL200 control arm received planned post-transplant maintenance. Non-relapse mortality was 2% (range 0-9%) in the BUMELVEL group and 10 (6%, range 3-11) in the MEL200 but this was not statistically significant in both univariate and multivariate modeling (p=0.25). There were no episodes of sinusoidal obstructive syndrome in the BUMELVEL group and 37% of patients experienced grade 3 mucositis with no grade 4 mucositis. After a median of more than seven years of follow up, the five year PFS was 47% (95% CI; 32-62) in the BUMELVEL group versus 30% (95% CI; 23-37) in the MEL200 group (p=0.05) (Figure 1). Notably the 7-year PFS in the BUMELVEL group was 32% (range 18-48). In multivariate analysis for PFS, BUMELVEL conditioning (HR 0.65; 95% CI 0.44-0.97)(p=0.036), time from diagnosis to transplant of greater than versus less than 12 months (HR 1.64; 95% CI 1.18 - 2.27), and disease status at transplant CR versus other (p=0.006) were all predictive of PFS (table 2). OS was not different between the two groups with a 7 year survival of 64% (95% CI; 48-79) in the BUMELVEL group versus 55% (95% CI; 46-64%) in the MEL200 group (Figure 1) which was confirmed on multivariate analysis (p=0.33). Discussion: Similar to recent reports in the literature comparing busulfan and melphalan to melphalan alone (Bashir et al, Lancet Hem 2019), we show that although depth of response was similar between the BUMELVEL group and the historical MEL200 comparator, the BUMELVEL group experienced an improved PFS. Importantly, we report no cases of SOS and a low non-relapse mortality of only 2% (v 6% in the historical control) reinforcing that the preparatory regimen in myeloma can be intensified safely with improved duration of unmaintained PFS. These long term results confirm a sustained benefit of novel combination conditioning in MM and the need for novel transplant preparative regimens. Disclosures D'Souza: EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio: Research Funding; Prothena: Consultancy; Pfizer, Imbrium, Akcea: Membership on an entity's Board of Directors or advisory committees. Hari:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria. Stiff:Unum: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Amgen: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding.

scholarly journals Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Real World Experience of a Single Center

2021 ◽  
Vol 27 ◽  
Author(s):  
A. Kopińska ◽  
A. Koclęga ◽  
A. Wieczorkiewicz-Kabut ◽  
K. Woźniczka ◽  
D. Kata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Checkpoint Inhibitors ◽  
Disease Status ◽  
Term Survival ◽  
Entire Cohort

Introduction: Refractory and relapsed Hodgkin lymphoma (R/R HL) is associated with poor prognosis, and allogeneic stem cell transplantation (allo-SCT) remains the only potentially curative approach.Aim: The aim of the study was to evaluate the feasibility of allotransplantation in R/R HL setting.Material: Overall, 24 patients (17 men and 7 women) at a median age of 27 years (range 18–44) underwent allo-SCT between 2002 and 2020.Results: Nineteen patients received prior autologous stem cell transplantation (ASCT1) whereas eight patients received second ASCT (ASCT2) after failure of ASCT1. Six patients received only brentuximab vedotin (BV; n = 4) or BV followed by checkpoint inhibitors (CPI; n = 2) before entering allo-SCT. Median time from ASCT1 to allo-SCT was 17.1 months. Fifteen patients received grafts from unrelated donors. Peripheral blood was a source of stem cells for 16 patients. Reduced-intensity conditioning was used for all patients. Disease status at transplant entry was as follows: complete remission (CR; n = 4), partial response (PR; n = 10), and stable disease (SD; n = 10). Acute and chronic graft-versus-host disease (GVHD) developed in 13 (54%) and 4 (16%) patients, respectively. Median follow-up for the entire cohort was 13.3 months. At the last follow-up, 17 (71%) patients died. The main causes of death were disease progression (n = 10), infectious complications (n = 6), and steroid-resistant GVHD (n = 1). Non-relapse mortality at 12 months was 25%. At the last follow-up, seven patients were alive; six patients were in CR, and one had PR. The 2-year overall survival (OS) was 40%.Conclusion: Chemosensitive disease at transplant was associated with better outcome. Allo-SCT allows for long-term survival in refractory and relapsed HL.

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.

Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1038-1038
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Allogeneic Stem Cell Transplant

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3077-3077
Author(s):  
Sascha Dietrich ◽  
Damien Roos-Weil ◽  
Ariane Boumendil ◽  
Emanuelle Polge ◽  
Jian-Jian Luan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

Impact of Antithymocyte Globulin-Containing Conditioning Regimens on Patients Undergoing Allogeneic Stem Cell Transplantation for Progressive Myelodysplastic Syndrome: A Report From the SFGM-TC Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3035-3035
Author(s):  
Ibrahim Yakoub-Agha ◽  
Gandhi Damaj ◽  
Marie Robin ◽  
Stephane Vigouroux ◽  
Alice Garnier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Refractory Disease ◽  
Advisory Committees ◽  
Grade 3

Abstract Abstract 3035 Background: due to a risk of relapse of underlying disease in patients transplanted with progressive malignancy, the use of antithymocyte globulins (ATG), incorporated within the conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), is still controversial. We report here on a study of 245 consecutive patients transplanted between January 1999 and December 2009 in 26 French and Belgian centers for progressive MDS, defined as stable, untreated, relapsed or refractory disease. Patients and Methods: Inclusion criteria included patients aged over 18 who received allo-SCT from either a sibling (n=153) or HLA-A, -B, -C, -DRB1 and -DQB1 allele matched unrelated donor (10/10) (n=86) for MDS or AML/RAEB-t (with 20–30% BM blasts). Data quality was ensured using computerized discrepancy errors and vigorous on-site data verification of every single file. A qualified research technicien has been appointed by the University-Hospital of Lille to assist on-site centers that couldn't meet data quality requirements. HLA matching was double-checked by the French Bone Marrow Donor Registry. Results: The first 239 files analyzed until now are presented, including 154 males and 85 females. According to the WHO classification at diagnosis, 85 patients had RA/RARS/RCMD, 86 RAEB1, 62 REAB2 and 6 RAEB-t/AML. Sixty-six patients had progressed to a more advanced disease before allo-SCT. At diagnosis, 102 patients had an IPSS int-2 or higher. Cytogenetic IPSS was recorded as favorable (n=109), intermediate (n=61), unfavorable (n=63) and missing (n=6). Disease status at transplant was established as follows: relapsed or refractory disease (n=106) and untreated or stable disease without hematological improvement (n=133). Median age at transplantation was 53 years (range, 20–70). Patients received myeloablative conditioning (n=105) and nonmyeloablative (n=134) including busulfan-based regimens (n=127), TBI-based regimens (n=92) or other alkylating-agent-based regimens (n=20). In this series, 95 patients (40%) received ATG as part of conditioning ('ATG' group), whereas 144 did not ('no-ATG' group). The analysis reference date of April 1st 2011, median follow-up in survivors was 50 months (IQR, 33–92) with 59 patients having died of relapse and 77 of TRM. The estimated 3-year OS and EFS was respectively 42.3%, and 32.4%. The probability of relapse, overall and event-free survival at 3 years was not significantly different between the two groups. In contrast, the cumulative incidence of grade 2–4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P <.001) and the cumulative incidence of grade 3–4 acute GVHD was 24% and 11% respectively (P <.001). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups (64% vs 46%, p=.15), a trend for a lower TRM was observed in the ATG group (22% vs 31%, p=.06). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of acute grade 2–4 [HR = 2.28, 95% CI: 1.39–3.74, p=.001] and grade 3–4 GVHD [HR = 2.19, 95% CI: 1.04–4.61, p=.035]. In conclusion, the addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising patient survival undergoing allo-SCT for progressive MDS. Disclosures: Yakoub-Agha: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding; Fresinus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Michallet:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Fresinus: Honoraria, Membership on an entity's Board of Directors or advisory committees. Deconinck:Celgene: Honoraria. Mohty:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Outpatient Non-Myeloablative Allogeneic Stem Cell Transplantation For Myeloma Is Feasible, Efficacious and Associated With Low Transplant-Related Morbidity and Mortality

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2128-2128
Author(s):  
Philip Campbell ◽  
Patricia A. Walker ◽  
Sharon Avery ◽  
Sushrut S. Patil ◽  
David J. Curtis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Disease Course ◽  
Entire Cohort ◽  
Co Morbidity ◽  
Significant Difference

Abstract Aim/Background Reduced intensity/non-myeloablative allogeneic haemopoietic stem cell transplantation (allo HSCT) for myeloma following a myeloablative autologous stem cell transplant (ASCT), is associated with lower TRM rates than myeloablative allografting and has the potential to induce long term disease control through the well documented graft-versus-myeloma effect. Continuing attempts to reduce the procedure-related toxicity as well as resource utilisation are likely to result in the use of curative tandem auto-allo earlier in the disease course. We retrospectively reviewed the outcomes of 33 outpatient tandem autologous/non-myeloblative (NMA) conditioning allo HSCT referred to our institution. Methods Between May 2008 and December 2012, 33 patients were referred for tandem auto-allo procedures. Patients were transplanted either upfront (n=18) as part of their initial management or as a deferred procedure (n=15), usually as salvage following an initial autograft followed by maintenance/consolidation. Patients were transplanted upfront if they had one or more of the following high risk features: t(4;14) or t(14;16) translocations, 1q amplification, 1p and 17p deletion on cytogenetics/FISH; elevated LDH; stage III ISS disease or less than a PR with a novel agent-containing induction regimen. Patients were eligible for tandem auto-allo if they had achieved at least a PR to the latest therapy, had no significant co-morbidity and were less than 70 years of age. All autografts were conditioned with melphalan 200mg/m2 and an outpatient NMA allo HSCT timed to occur 3 months later using oral fludarabine 48mg/m2 on days -4 to -2 and 2Gy TBI on day 0 as conditioning. A target cell dose of 2 x 106/kg CD34+ donor stem cells were infused on day 0. Graft versus host disease prophylaxis consisted of cyclosporine and mycophenolate mofetil. Results The median age for the entire cohort was 52 (range 39-65), 19 males and 15 females and the median follow up was 719 days (50-1733). The overall response rate post-allo HSCT was 26/33 (79%) with a significantly higher proportion of CR/VGPRs seen in those transplanted upfront rather than deferred (15/18 v 7/15; p=0.03). The majority of patients were transplanted as outpatients (29/33) and only 4 were admitted for social reasons. Transplant complications requiring admission in the first 30 days occurred in 15/33 (45%) of patients, with a median length of stay of 1.5 days, and only 4 patients were hospitalised for more than 7 days. Median nadir neutrophil and platelet counts were 0.5 x 109/L (range 0.1-1.1) and 94 x 109/L ( range 23-143) respectively across the entire cohort and no patient experienced graft failure. Acute GVHD occurred in 14 (44%) of patients, was mild in the majority of cases and only 3 (9%) developing severe GII-IV aGVHD. Manageable chronic GVHD occurred in 19/31 (61%) evaluable patients, there were no transplant-related deaths by day 100 and 2 patients died of infection (microbiologically-unconfirmed sepsis at day 240 and disseminated nocardia infection at day 1025), resulting in a TRM of 6%. At the time of analysis, 26 (79%) patients were alive including 15 (45%) in ongoing CR. The median OS for the entire cohort has not been reached and the median PFS for all patients is 2.8years. Patients allografted upfront had significantly longer PFS compared to those recipients of a deferred transplant procedure (median NR versus 1.2 years respectively; p=0.03) but there was no significant difference in OS at 2 years follow up. Conclusion Tandem autologous/NMA allo HSCT for myeloma, when performed in the ambulatory setting, is feasible, well tolerated and associated with minimal toxicity and low TRM. Our results with outpatient tandem auto-allo compare favourably with ASCT and suggests allo HSCT may benefit selected patients earlier in their disease course. Disclosures: Spencer: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

A Comparison of the Outcomes of Early Versus Delayed Autologous Stem Cell Transplantation for Multiple Myeloma in the Era of Novel Therapies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1993-1993
Author(s):  
Siyang Leng ◽  
Erin Moshier ◽  
Douglas Tremblay ◽  
Noa Biran ◽  
Naman Barman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Research Funding ◽  
Institutional Research ◽  
Novel Therapies ◽  
Time To Progression ◽  
Landmark Analysis ◽  
Group 1

Abstract Background: In phase 3 studies comparing high dose melphalan (mel) with autologous stem cell transplantation (ASCT) to conventional chemotherapy, ASCT improves progression free survival (PFS) and, in some studies, overall survival (OS). However, these studies were performed before the use of potent, novel induction therapies such as bortezomib (V), lenalidomide (R), and dexamethasone. The optimal timing and benefit of ASCT in the era of novel therapies is unknown. In our program, upon completion of stem cell harvest (SCH), some patients elect to delay ASCT after discussion of risks and benefits. The aim of this retrospective study is to compare the time to progression (TTP) and OS of patients who proceeded to ASCT early as consolidation of initial therapy, versus ASCT delayed until relapse. While data from prospective studies are eagerly awaited, this retrospective study has the advantage of a long follow up. Methods: In this IRB approved, retrospective case series, electronic medical records of all patients with symptomatic MM who had SCH at Saint Vincent's Medical Center or Mount Sinai Hospital between 1/1/2005 to 6/30/2014 were reviewed. Patients were divided into the following groups: Time to progression (TTP) is calculated using Kaplan-Meier analysis. OS is calculated using a landmark analysis at 2 and 3 years after diagnosis. Results: 572 consecutive patients were identified. 18 were excluded for incomplete data. Baseline characteristics are shown in Table 1. The groups did not differ significantly in terms of stage (either Durie Salmon or International Staging System), disease isotype, or high risk disease features (defined by cytogenetics or FISH as amp 1q, t(14;16), t(14;20), del 17p13). The median follow-up for the entire group was 47.5 months. Not surprisingly, the median TTP after ASCT diminished with delay of ASCT, from 28.4 mo for early ASCT to 12.2 mo for delayed (p < 0.001). That said, when comparing groups 1 and 2, there was no difference in the median time from diagnosis to progression after mel 200 mg/m2 ASCT Ð 39.1 vs 43.6 mos (p = 0.945). Using landmark analysis starting at 2 years from diagnosis, the median OS was 61.3, 37.4, 18.9, and 116.7 for groups 1, 2, 3, and 4 respectively (p = 0.087 for group 1 vs 2; p < 0.001 for group 1 vs 3; Figure 1). Landmark analysis at 3 years from diagnosis showed median OS of 50.3, 56.5, 13.9, and not reached (p = 0.41 for group 1 vs 2; p < 0.001 for group 1 vs 3). Conclusions: There are three findings of interest. 1) TTP in those who underwent early ASCT was 15 months longer than those who underwent ASCT at relapse. 2) TTP after SCT was comparable in groups 1 and 2, which may be attributable to the preferential use of maintenance chemo either pre or post ASCT, respectively. 3) The rank ordering of median OS by landmark analysis suggests an interplay between therapy and disease biology Ð many patients may do very well without SCT, perhaps due to durable remissions with novel regimens. The remaining groups demonstrate a striking decrease in OS as the number of relapses in a given time period increases, indicating the need for novel approaches to MM that behaves in clinically aggressive manner. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Biran: Celgene: Speakers Bureau. Jagannath:Celgene: Honoraria; Merck: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria. Chari:Onyx: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Biotest: Other: Institutional Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Consultancy, Other: Institutional Research Funding, Research Funding; Novartis: Consultancy, Research Funding.

Alternative Donors (Umbilical Cord Blood and Haploidentical Donors) for Allogeneic Stem Cell Transplantation in Relapsed / Refractory Hodgkin Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party and the Spanish Group of Stem Cell Transplantation (GETH)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4399-4399 ◽  
Author(s):  
Carmen Martinez ◽  
Jorge Gayoso ◽  
Carmen Canals ◽  
Herve Finel ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Hematopoietic Stem ◽  
Number Of Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

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