scholarly journals Allogeneic Stem Cell Transplantation in Myelodysplastic Syndrome; A More Favorable Outcome after Fludarabine and Treosulfan Conditioning. a Survey on Behalf of the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1216-1216
Author(s):  
Avichai Shimoni ◽  
Arnon Nagler ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Dietrich Beelen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Research Funding ◽  
Working Party ◽  
Unrelated Donor ◽  
Refractory Disease ◽  
Predicting Factors ◽  
History Of ◽  
Relapse Rates

Abstract Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients with myelodysplastic syndrome (MDS). So far, there is no proven advantage for any conditioning regimen over the others. Prior studies have shown that reduced-intensity conditioning (RIC) is associated with lower non-relapse mortality (NRM) compared with myeloablative conditioning (MAC), however, relapse rates are increased, resulting in similar survival. Novel conditioning regimens that will reduce SCT-related toxicity while retaining maximal anti-leukemia effect will be of benefit. Fludarabine combined with treosulfan (FT) has been shown, in relatively small phase II studies, to be a reduced-toxicity regimen with intense anti leukemia activity and limited toxicity in patients with myeloid malignancies and possibly in particular in MDS. In this analysis we performed a retrospective analysis of all SCTs for MDS, performed between 2000 and 2011 and reported to the chronic malignancies working party (CMWP) of the EBMT (n=2516). We identified 480 patients given FT and compared their outcomes to patients given various MAC (n=1090) and RIC (n=946) regimens. FT and RIC recipients were older than MAC recipients, median age 59, 60 and 50 years, respectively (p=0.001). They were also more likely to have an unrelated donor, 56%, 57% and 50%, respectively (p=0.001) and to be given peripheral blood stem cell rather than bone marrow grafts, 92%, 94% and 79%, respectively (p=0.001). More FT recipients had previously untreated MDS at SCT, 33%, 20% and 24% while less had chemosensitive disease, 42%, 51% and 51%, respectively (p=0.001). The proportion of patients with chemo-refractory disease and with more than 10% marrow or peripheral blood blasts at SCT was similar in the three groups. More FT recipients had a prior history of transformation to AML, 15%, 9% and 9%, respectively (p=0.03). The proportion of patients with high and intermediate-risk cytogenetics was 13%, 21% and 18%, respectively (p=0.01). With a median follow-up of 21 months (range, 1-150), 1364 patients are alive, 456 patients died of relapse and 696 of NRM causes. The estimated 5 year overall (OS) and disease-free (DFS) rates for the entire group were 40% (95%CI, 37-43) and 35% (95%CI, 33-38), respectively. The 5-year OS rate of FT recipients was 47% (95%CI, 41-52). OS after the various RIC and MAC regimens was similar, 39% (95%CI, 34-43) and 38% (95%CI, 33-42), respectively, significantly shorter than after FT (p=0.02). DFS rates were 42% (95%CI, 37-47), 31% (95%CI, 27-36) and 35% (95%CI, 30-39), respectively (p=0.002). Relapse rates were similar after FT and MAC, 25% (95%CI, 21-30) and 29% (95%CI, 25-33), respectively, significantly lower than after RIC, 37% (95%CI, 33-41) (p=0.001). NRM was lower after FT and RIC than after MAC, 33% (95%CI, 28-38) and 32% (95%CI, 28-35), Vs. 36% (95%CI, 33-40), respectively (p=0.14). Multivariate analysis identified age> 55 years (HR 1.7, P=0.01), marrow blasts at SCT > 10% (HR 1.5, p=0.02), a history of transformation to AML (HR 1.7, p=0.01) and MDS refractory to prior therapy (HR 1.8, p=0.001) as poor prognostic factors for survival, while FT conditioning was protective (HR 0.6, p=0.02). Gender, cytogenetics, time from diagnosis to SCT, donor type and stem cell source were not predictive for survival. The predicting factors for increased relapse risk were RIC (HR 1.6, p=0.03), chemorefractory disease (HR 1.6, p=0.05), marrow blasts at SCT > 10% (HR 1.6, p=0.04), poor risk cytogenetics (HR 2.2, p=0.003) and prior transformation to AML (HR 1.8, p=0.0001). The predicting factors for increased NRM were MAC (HR 1.6, p=0.004), age > 55 years (HR 1.5, p=0.008), unrelated donor (HR 1.4, p=0.004), chemo-refractory disease (HR 1.5, p=0.05), marrow blasts > 10% (HR 1.6, p=0.01) and positive patient serology for CMV (HR 1.4, p=0.04). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved outcome over both RIC and MAC regimens. FT might be the preferred regimen for SCT in MDS. These observations merit further study in randomized prospective trials. Disclosures Nagler*: MEDAC, Germany: Honoraria, Research Funding. Beelen:MEDAC, Germany: Research Funding. Ciceri:MEDAC, Germany: Honoraria, Research Funding. Kröger:MEDAC, Germany: Research Funding.

Impact Of Induction Regimen and Consolidative Stem Cell Transplantation In Patients With Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 640-640 ◽  
Author(s):  
Mitul Gandhi ◽  
Adam M. Petrich ◽  
Ryan D. Cassaday ◽  
Oliver W. Press ◽  
Khushboo Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Retrospective Analysis ◽  
Research Funding ◽  
Refractory Disease ◽  
Indolent Lymphoma ◽  
Off Label ◽  
Induction Regimen ◽  
History Of

Abstract Background DHL are high-grade B-cell lymphomas (BCL) characterized by dual gene rearrangements (RA) of MYC and either BCL2 or BCL6. Outcomes are typically dismal, particularly when treated with R-CHOP, as compared to those observed in patients (pts) with similar histologies without dual RA. Few reports have evaluated the use of intensive induction regimens, with or without consolidative stem cell transplantation (SCT). We sought to evaluate the role of intensive induction as well as SCT, and to investigate predictors of outcome in DHL. Methods This study was an IRB-approved retrospective analysis across 15 centers. Cases were diagnosed between 2000-2012 as aggressive BCL harboring RA, by FISH, of MYC along with RA of BCL2 and/or BCL6. Pts were treated with either R-CHOP, or one of the following intensified regimens: R-HyperCVAD, R-EPOCH, R-CODOX-M/IVAC, R-ICE. Survival was estimated using Kaplan Meier method, and comparisons made with log rank test. Multivariable analysis (MVA) was performed using the Cox proportional hazard regression. Results One hundred six pts were analyzed. Median age at diagnosis was 60; 59% were male. The majority had DHL characterized by RA of MYC and BCL2 (77%); the remainder showed RA of MYC and BCL6 (10%), or all three (12%). History of indolent lymphoma was present in 29 pts (27%). The most common histology was DLBCL in 56 pts (53%), followed by BCL unclassifiable (BCLU) in 45 (42%), and Burkitt-like in 5 (5%). Thirty six pts (33%) received R-CHOP, 33 (31%) R-EPOCH, and 28 (36%) R-Hyper-CVAD or CODOX-M/IVAC. Fourteen pts (13%) were consolidated with SCT (n=1 allo and n=13 auto SCT); all were treated with intensive induction. Three additional pts underwent SCT in partial remission or progressive disease following R-CHOP induction. The median PFS and OS for the entire cohort were 8.8 mo and 12 mo, respectively (Table 1); of the 24 pts (23%) alive and without progression, median follow-up was 19 mo. R-EPOCH was superior in achieving complete response (CR) compared with R-CHOP (P 0.01), and trended towards significance compared with pts receiving other intensive induction (P 0.07). Additionally, primary refractory disease, observed in 37 pts (34.5%), occurred less frequently in pts receiving R-EPOCH compared to R-CHOP (P .005) or other intensive regimens (P 0.03); induction regimen did not impact OS in patients not receiving SCT (P 0.7; Fig 1). SCT in first remission was associated with improved OS (P 0.02), and PFS (P 0.006) compared with induction alone. However, among pts achieving CR, SCT was not associated with improved OS compared with observation (P 0.22; Fig 2). Pts with prior history of indolent NHL did not fare worse than those with de novo DHL (P 0.5). No difference in OS was observed based on histology (P 0.2). The following factors were evaluated in MVA: prior indolent lymphoma, histological subtype, IPI>/=3, primary refractory disease, type of induction (R-CHOP vs intensified), and consolidative SCT. Only primary refractory disease (P<0.0001) predicted for inferior OS. Consolidative SCT did not improve OS on MVA (P 0.13). Conclusions In this analysis of DHL, primary refractory disease was the primary predictor of OS. Pts achieving CR did not appear to benefit from consolidative SCT, though our analysis was limited by the fact that pts receiving SCT are often highly selected (for chemosensitivity, age, comorbidities) and in this study, by the low number of pts receiving SCT. R-EPOCH was associated with a decreased rate of primary refractory disease compared to other regimens, and increased rate of CR compared to R-CHOP, but the lack of clear survival benefit suggests that relapsed disease offsets early benefit. Our analysis confirms the generally poor outcomes for pts with DHL, though a subset with chemosensitive disease has an improved prognosis, likely due to favorable disease biology. Further investigation on the role of SCT and of novel agents is needed for this high-risk population. ^Three patients untreated, one received multiple regimens Disclosures: Off Label Use: Brentuximab Vedotin is approved for relapsed, refractory Hodgkin Lymphoma in patients who have already had a transplant or are ineligible for one, or for patients with relapsed, refractory anaplastic large cell lymphoma. Patients treated on clinical trials or off label will be included in this presentation. Petrich:Genetech: Consultancy, Honoraria. Fenske:Seattle Genetics : Consultancy, Honoraria. Smith:Seattle Genetics, Inc.: Research Funding; Spectrum: Consultancy; Cephalon: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; GlaxoSmith Kline: Speakers Bureau. Evens:Seattle Genetics: Consultancy, Honoraria; Millennium: Consultancy, Honoraria, Research Funding; Ziopharm, Inc: Research Funding; Celgene: Consultancy, Honoraria.

scholarly journals Reduced Intensity Vs. Standard Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with MDS or Secondary AML: A Prospective, Randomized Phase III Study of the Chronic Malignancies Working Party of the EBMT (RICMAC-Trial)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 320-320 ◽  
Author(s):  
Nicolaus Kröger ◽  
Ronald Brand ◽  
Dietger Niederwieser ◽  
Uwe Platzbecker ◽  
Kai Hübel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Randomized Trial ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Working Party ◽  
Unrelated Donor ◽  
Reduced Intensity

Abstract Introduction Retrospective studies in MDS/sAML suggest that reducing the intensity of the conditioning regimen prior to allogeneic stem cell transplantation reduces the risk of non-relapse mortality but is associated with a higher risk of relapse, but prospective randomized studies for MDS are lacking so far. Patients and Methods Within the Chronic Malignancies Working Party (CMWP) of EBMT, we performed a prospective randomized trial comparing a busulfan based (Busulfan 8mg/kg orally or equivalent dosis intravenously (iv) plus fludarabin 180mg/m²) reduced intensity conditioning regimen (RIC) and a standard myeloablative busulfan (Busulfan 16mg/kg orally or equivalent dosis iv plus cyclophosphamide 120mg/kg) based regimen (MAC) in patients with MDS or sAML (<20 % blasts). Between May 2004 and December 2012, 129 patients were included from 18 centers and 7 nations and 127 could be analysed. Major inclusion criteria were: MDS (according to FAB: RA, RARS, RAEB, RAEB-t), CMML, and sAML, blasts less than 20 %, matched related or unrelated donor (HLA 8/8, 1 mismatch was allowed), age 18 - 60 years (for unrelated) and 18 - 65 years (for HLA-identical sibling). Included patients were stratified according related vs unrelated donor and blast count < or > than 5%. The primary endpoint of the study was 1 year non-relapse mortality.The median age of the patients was 51.4 years (r.19-64y). Donors were HLA-identical sibling (n=34), matched unrelated (n=59) and mismatched related or unrelated (n=30). The patients were well distributed in both arms regarding age, gender, IPSS risk profile, number of blasts at transplantation, donor source and mismatch donor. Results Leukocyte count more than 1.0 x 10e9/L and platelet count more than 50x10e9/L at day 28 was reached in 90 % and 70% after RIC and in 92% and 77% after MAC, respectively Acute GvHD II-IV was noted in 29% after RIC and 32% after MAC. Chronic GvHD was seen in 61% after RIC and 64% after MAC. The cumulative incidence (CI) of non-relapse mortality (NRM) after 1 year was 17% (95% CI 8-26%) after RIC and 28% (95% CI 16-39%) after MAC (p=0.18). The CI of NRM at 1 year after HLA-identical sibling transplantation was lower than after unrelated transplantation after RIC (0% vs 23%, p=0.06) as well after MAC (17% vs 32%; p=0.18) The CI of relapse at 2 years was 18% (95% CI 8-27%) after RIC and 15% (95% CI 5-24%) after MAC (p=0.5), resulting in a 2 year relapse-free and overall survival of 61% (95% CI 48-73%) and 74% (95% CI 63-86%) after RIC and 56% (95% CI 43-69%) and 61% (95% CI 48-73%) after MAC (p=0.50 and p= 0.07, respectively). Conclusion This prospective randomized trial of EBMT provide evidence that RIC resulted in at least similar 2 year relapse-free and overall survival as in MAC for patients with MDS and sAML and less than 20% blasts. Disclosures Kobbe: Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Medac: Other; Astellas: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Other.

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.

scholarly journals Haploidentical Stem Cell Transplantation in Patients with Myelodysplastic Syndrome: Case Report First Experience

2021 ◽  
Vol 9 (C) ◽  
pp. 250-253
Author(s):  
Aleksandra Pivkova-Veljanovska ◽  
Irina Panovska-Stavridis ◽  
Lazar Chadievski ◽  
Sanja Trajkova ◽  
Marija Popova-Labachevska ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
High Risk Patient ◽  
Unrelated Donor ◽  
Case Presentation ◽  
Haploidentical Stem Cell Transplantation

  BACKGROUND: Allogeneic stem cell transplantation (ASCT) is a potentially curative therapeutic approach in patients with intermediate and high-risk myelodysplastic syndrome (MDS). If a family sibling or unrelated donor is not available mismatched donors are viable option for young patients with no comorbidities. The aim of this case presentation was to evaluate our first experience with haploidentical transplantation for this indication. CASE PRESENTATION: We present a case of 50 years male patient with myelodysplastic syndrome (MDS) diagnosed at University Clinic for hematology, Skopje, North Macedonia. Patient was scored in IPSS -R as high risk patient. He was referred for HLA DNA typing of family siblings and since he didn’t have identical sibling and unrelated donor, he was referred to continue treatment with haploidentical stem cell transplantation. He received Flu Bu conditioning and PTCY, cyclosporine and MMF for GVHD prophylaxis. Peripheral blood stem cells (PBSC) from his mismatched brother were infused in the amount of CD34=5.8x106/kg. He experienced prolonged engraftment, severe infective bacterial infections and CMV reactivation with clinical manifestation of CMV colitis. He was successfully treated with antiviral drug and completely resolved. His bone marrow analysis showed complete remission and chimerism evaluation revealed high donor engraftment. Patient is now +34 months post transplant in complete remission. CONCLUSION: The use of a mismatched donor increases the risk of NRM, but there is also evidence to suggest that an haploidentical donor is a valid choice, as general outcome appears to be at least similar to MUD.

Secondary Monoclonal Gammopathy of Undetermined Significance after Allogeneic Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1238-1238
Author(s):  
Marian Schmitz ◽  
Henny Otten ◽  
Laurens Franssen ◽  
Suzanne van Dorp ◽  
Theo Strooisma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Protein Band ◽  
M Protein ◽  
Unrelated Donor

Abstract Background In the course of multiple myeloma (MM), patients may develop monoclonal bands of different isotypes than the original myeloma M-protein. Several terms have been used to describe this phenomenon, including abnormal protein band, oligoclonal protein bands, transient mono- or oligoclonal gammopathy, oligoclonal humoral response, atypical serum immunofixation pattern, and in myeloma patients, as we will use in this study, secondary MGUS (sMGUS). There are currently no data available regarding the frequency of sMGUS and its prognostic significance in MM patients who underwent allogeneic stem cell transplantation (allo-SCT). Here, we describe the occurrence of sMGUS and its association with response, progression-free survival (PFS), and overall survival (OS) in this group of patients. Study design We included a total of 138 patients who underwent 139 allo-SCTs (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma). All patients received their allo-SCT in the University Medical Center Utrecht. Secondary MGUS was defined as appearance of a protein band on immunofixation or electrophoresis that is different from the original myeloma M-protein in heavy-chain or light-chain isotype, or in its migration pattern. Results Sixty-seven (48.2%) patients developed at least one sMGUS after allo-SCT with a median latency of 6.9 months. Twenty-five patients had only one new protein band (18.0%), 9 (6.5%) had 2 bands, 8 (5.8%) had 3 bands, and 25 (18.0%) had four or more. The median duration of all sMGUS cases was 4.47 months (range 0.0-74.5 months). There was no progression of sMGUS to MM or other lymphoproliferative diseases. Secondary MGUS occurred more often in patients who achieved at least very good partial response after allo-SCT, compared to partial response or less (54.8% vs 26.5%, P=0.005). The incidence was also higher in the upfront setting as compared to patients with relapsed disease (60.0% vs 40.5%; P=0.037), or with a sibling donor compared to matched unrelated donor (57.0% vs 36.7%, P=0.026), but less often after T cell depletion (39.3% vs 61.8%, P=0.025). Importantly, development of post-transplant MGUS as a time-dependent variable, independently predicted for superior PFS and OS (median PFS: 37.5 vs 6.3 months, P<0.001; median OS: 115.3 vs 31.0 months, P=0.004). Since most TRM occurred in the first 6 months after allo-SCT (12 out of 15 TRM cases; 80%), we also performed a landmark analysis at this time-point. PFS and OS remained significantly superior in patients with sMGUS (n=100 patients; median PFS: 31.5 vs 4.9 months, P<0.001; median OS: 109.3 vs 57.3 months, P=0.015). Importantly, development of sMGUS was associated with improved PFS and OS both in patients who received allo-SCT as part of first-line treatment and in patients with relapsed MM. In addition, emergence of sMGUS predicted for enhanced PFS and OS in patients who achieved at least VGPR and also in patients who achieved less than VGPR after allo-SCT. Conclusions This is the first study that evaluates the significance of sMGUS in MM patients treated with allo-SCT. Development of sMGUS after allo-SCT was associated with a better quality of response, as well as significantly improved PFS and OS, both in patients transplanted in the upfront setting and at the time of relapse. Clinicians should be aware of the benign nature of this phenomenon, and sMGUS should not be confused with relapse or progression of disease. Disclosures Lokhorst: Celgene: Research Funding; J&J: Research Funding; Genmab: Research Funding. van de Donk:Celgene: Research Funding; J&J: Research Funding; Onyx: Research Funding.

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.

Matched Unrelated Donor Stem Cell Transplantation for Patients with Diffuse Large Cell B Cell Lymphoma: A Retrospective Analysis of 118 Patients Registered through the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 602-602 ◽  
Author(s):  
Irit Avivi ◽  
Carme Canals ◽  
Goli Taghipour ◽  
Dietger Niederwieser ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Unrelated Donor ◽  
Refractory Disease ◽  
Matched Unrelated Donor ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Matched unrelated donor stem cell transplantation (MUD-SCT) may provide a treatment option for patients with diffuse large B cell lymphoma (DLBC) who have failed other conventional therapies and do not have a compatible sibling donor available. We present data of 118 DLBC patients, 69 males and 49 females, aged 18 to 66 years (median 43 years), treated with a MUD-SCT between January 1997 and July 2005 and reported to the EBMT registry. Median time from diagnosis to MUD-SCT was 25 months (range, 3 – 205), and 64% of the cases had failed a previous autologous transplant (ASCT). At allogeneic transplantation, 25% of the patients had chemorefractory disease. Peripheral blood was the source of hematopoietic stem cells in 70% of the cases and reduced intensity conditioning regimens (RIC) were used in 52% of the cases. After a median follow up of 26 months, the estimated 2-year non-relapse mortality (NRM), relapse rate (RR), progression free survival (PFS) and overall survival (OS) for the whole series were 29%, 35%, 36% and 43%, respectively. Grade II–IV acute graft-versus-host-disease developed in 32% of patients. Patients selected for RIC protocols were older (median age of 44 years vs 38 years, p = 0.02) and more heavily pre-treated; 75% had failed a previous autograft compared with 53% in the conventionally treated group (CC) (p = 0.01). Despite these unfavorable factors, the 2-yr NRM for RIC patients was significantly lower than in CC patients: 19% vs 39% (p = 0.03). Unfortunately, this advantage was offset by an increased RR in this group of patients (2-yr RR: 46% vs 24%, p = 0.2), resulting in a very similar PFS and OS for both types of conditioning regimens. The prognostic factor with highest impact on PFS was refractory disease at transplantation (RR = 1.8; 95%CI 1.1 −3.1, p = 0.02). The 2-year PFS for patients transplanted with sensitive disease was 40% irrespective of the conditioning regimen used. In sensitive patients undergoing a RIC transplant, the NRM was significantly lower with respect to CC regimen (14% vs 38%, p = 0.02), resulting in an improved PFS and OS (41% vs 37% and 50% vs 46% respectively). PFS in patients transplanted with refractory disease was generally poor (25% at 2 years). However, CC seemed to provide a better outcome than RIC (2-yr PFS of 35% vs 16%). In conclusion, MUD-SCT constitutes a treatment option for patients with DLBCL failing other conventional treatments, particularly for those patients being allografted in sensitive disease. The high RR observed with reduced intensity protocols does not allow to demonstrate a clear long-term benefit of this approach in this setting.

Older Patients with Hodgkin Lymphoma (HL) Undergoing Autologous Stem Cell Transplantation for Relapsed/Refractory Disease Have Inferior Survival Compared to Younger Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4521-4521
Author(s):  
Akshay Sharma ◽  
Minghui Duan ◽  
Michael Graiser ◽  
Hongzheng Zhang ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Bimodal Distribution ◽  
Refractory Disease ◽  
Seer Database ◽  
Younger Patients ◽  
The Mean

Abstract Abstract 4521 Background: About 1/3 of advanced Hodgkins lymphoma (HL) patients fail first line therapy and are candidates for autologous stem cell transplantation (ASCT). Studies describing the outcomes of relapsed/refractory HL in adults have shown that the long-term survival is about 40–60%, following treatment with high dose chemotherapy and ASCT. Surveillance, Epidemiology and End Results (SEER) data indicates that children/adolescents with HL have different disease characteristics from adults (Bazzeh et al, Leukemia and Lymphoma 2010), which we hypothesized could lead to different ASCT outcomes. The aim of this study was to describe the demographic distribution of relapsed/refractory HL patients requiring ASCT at a major transplant center and to study the overall survival (OS) post ASCT with age as a covariate. Patients and Method: We performed an IRB approved, retrospective analysis of a combined cohort of adult and pediatric HL patients undergoing ASCT at Winship Cancer Institute at Emory University and Children’s Healthcare of Atlanta from 1995 to 2011. A total of 131 patients were included in the study (adult=112, pediatric=19). Demographics of patients include: 54% male, 65% Caucasians, 26% African American. The mean age of diagnosis was 30 ± 12 years and the mean age at transplant was 33 ± 13 years. Patients were divided into two categories, younger (≤35 years, n=96) and older (>35 years old, n=35), based on the bimodal distribution of the incidence of HL observed in the SEER database (first peak in the age group 15–35 years and the second one around 55 years). Overall survival was compared using Kaplan Meier estimates for the time-to-event analysis and log rank test for comparing the two groups. Predicted survival for individuals of different ages (in the absence of cancer) was derived from Social Security Administration life tables. Result: As expected from the incidence data in the SEER database, there was a bimodal distribution of age at diagnosis among HL patients undergoing ASCT for relapsed/refractory disease, with a first peak at 25 years and the second peak at 46 years [Figure 1]. 75% patients had nodular sclerosing histology, 8% had mixed-cellularity and 6% had the lymphocyte predominant histological subtype. The distribution of histological subtypes did not differ by age. A univariate analysis revealed that patients with age > 35 years had significantly higher post-transplant mortality (p=0.037) than those ≤35 years [Figure 2]. A multivariable model that included age ≤35, histology, disease status at transplant and chemo-sensitivity indicated that only one of these variables (age) was explanatory in the model. Conclusion: As expected by the increased suitability of ASCT for younger patients, the number of patients ≤35 years undergoing ASCT for refractory/relapsed HL was much higher than the number of older patients. Overall survival of older HL patients who underwent ASCT was worse than that for younger HL patients, likely due to differences in supportive care, toxicity from treatments, and comorbid diseases. The age related differences in post-transplant survival were not explained by the decreased actuarial life expectancy of older subjects based upon life-table projections of survival for the general population. The bimodal distribution in the incidence of HL, and the inferior survival of older HL patients undergoing ASCT suggests that there may be differences in the biology of the disease based upon the age at which HL is diagnosed. Alternative strategies for autologous transplantation of older patients with relapsed/refractory HL are needed. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Novartis: Research Funding; Seattle Genetics: Consultancy.

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