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.

Allogeneic Stem Cell Transplantation in Patients ≥70 Years Old

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2309-2309
Author(s):  
Christopher C Walling ◽  
Pamela A Shaw ◽  
Noelle V Frey ◽  
Saar I Gill ◽  
Elizabeth O. Hexner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Age Groups ◽  
Hematopoietic Stem ◽  
Younger Patients ◽  
Allogeneic Hsct

Abstract Background: While reduced intensity conditioning has allowed older patients to undergo allogeneic hematopoietic stem cell transplantation (HSCT) for a variety of hematologic malignancies, age is still viewed as a relative contraindication. In particular, only limited and conflicting data are available on outcomes of patients ≥ 70 years old. Methods: To determine outcomes and utility or futility of transplant for "older" patients, we conducted a retrospective study of all patients 65 and older who underwent allogeneic SCT at our institution between March 2002 and March 2015. 33 patients age 70-75 (median 71 years) were compared to 95 concurrent allogeneic HSCT recipients age 65-69 (median 67). Results: The two groups (70-75 and 65-69) were similar in terms of donor type (70% URD 30% MRD vs. 67% URD 27% MRD 3% cord blood, p=0.86), conditioning regimen (75% flu/bu vs. 65% flu/bu, p =0.26), HCT-CI scores (mean 2.7 vs 2.9, p=0.29), disease phase (9% vs. 15% with primary refractory/active disease, p=0.651) and disease distribution (AML/MDS in 76% and 80%, p=0.7). The OS for all patients was 51% at 1 year and 38% at 2 years, with a median follow up of 13.1 mo and no differences between age groups (fig 1, p=0.70). The median survival was 12.5 months in the 70-75 group vs. 13.7 months in the 65-69 group. As seen in Table 1, transplant was well tolerated and outcomes similar between both age groups with minimal 30 day mortality. Comparing patients age 70-75 to those 65-69, there was no difference in OS at 100d, 1 year or 2 years. There was no difference in grade II-IV acute GVHD (p=0.50). The cause of death was similar in both groups; of the patients who died, death was treatment-related in 45% and 40% of 70+ versus younger patients respectively, largely due to GVHD and infection. Relapse accounted for death in 55% and 57% of older versus younger patients who died. Conclusions: These data suggest that at least selected patients ≥70 years old can tolerate allogeneic HSCT similar to patients ages 65-69. Outcomes in both age groups remain limited by a high risk of relapse highlighting that better methods for tumor control are needed such as post-transplant maintenance or novel disease-specific strategies that minimize GVHD but allow for enhanced GVL induction. However age ≥70 should not be an absolute contraindication for transplant. Figure 1 Figure 1. Disclosures Shaw: Vitality Institute: Research Funding; Novartis: Research Funding. Frey:Servier: Consultancy; Amgen: Consultancy; Novartis: Research Funding. Gill:Novartis: Patents & Royalties, Research Funding. Luger:Astellas: Honoraria; Dava Oncology: Honoraria; Pfizer: Consultancy; Onconova: Other: Clinical Trial --Institutional PI; Seattle Genetics: Other: Clinical Trial--Institutional PI; Ariad: Other: Clinical Trial--Institutional PI; Celgene: Other: Clinical Trial--Institutional PI; Cyclacel: Other: Clinical Trial, Institutional PI. . Mangan:Novartis: Research Funding; Incyte: Other: Advisory Board. Stadtmauer:Celgene: Consultancy; Takeda: Consultancy; Teva: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Amgen: Consultancy. Porter:Genentech: Other: Spouse Employment; Novartis: Patents & Royalties, Research Funding.

Autologous Stem Cell Transplantation for Multiple Myeloma in Patients over 70 Years: A Matched Comparison with Patients under 65 Years.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1173-1173
Author(s):  
Shaji Kumar ◽  
Martha Lacy ◽  
Angela Dispenzieri ◽  
Suzzane Hayman ◽  
William Hogan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Older Patients ◽  
Control Group ◽  
High Dose ◽  
High Dose Therapy ◽  
Younger Patients ◽  
Dose Therapy

Abstract Background: High dose therapy with autologous stem cell rescue has been shown to prolong survival in patients with multiple myeloma in randomized controlled trials. However, most of the prospective studies have included younger patients, usually 65 or less. It is important to have a better understanding of the outcome of transplantation in the older patients given the median age of onset of myeloma of 65 years. We retrospectively reviewed our institutions experience with high dose therapy for patients over 70 years. Methods: We identified 35 patients with multiple myeloma, from the transplant database, who were at or over the age of 70 at the time of their high dose therapy. We matched these patients to 70 patients (two matches for each patient), based on stage at transplant (primary refractory, plateau phase, relapse off therapy, or relapse on therapy), Durie Salmon stage, high or low labeling index, conventional cytogenetics (abnormal vs normal), presence or absence of circulating plasma cells at time of transplant, and whether cyclophosphamide was used as part of mobilization in that order of priority. Results: The median age of the two groups were 55.3 (Range 37.3–64.8) and 71.7 (Range 70–75.8) years at the time of transplant. The median time to transplant from diagnosis was similar (6.4 for the older patients compared to 6.9 months for the other, P = NS). Ten of the 35 older patients received reduced dose melphalan (140 mg/2)) compared to 3 patients in the control group; P < 0.01. The median follow up from transplant was 10.1 months for the older patients compared to 18 months for the control group. The overall response rate was similar for the two groups (97.1% for the older patients compared to 95.5 for the control group). Eleven (31%) of the older patients and 17 (24%) of the control patients achieved a CR (P = NS). The post transplant progression free survival estimate at 1 year post transplant was 65.3% for the older patients compared to 66% for the control group (P = 0.3)The two year estimated overall survival from transplant was similar in the two groups; 58% for the older patients compared to 67% for the control group. The overall survival from diagnosis was similar for the two groups (P = 0.6). The median number of days hospitalized was 9 days for the older population compared to 5 days for the control group (P = 0.37). Four patients died within the first one hundred days, one (3%) among the older patient group and 3 (4.3%) in the control group. Conclusions: High dose therapy and autologous stem cell transplantation is feasible in selected patients with multiple myeloma over 70 years. It is likely that these older patients were selected based on their overall performance status, a factor that is difficult to analyze in this retrospective review. Nearly 70% of the elderly patients received full dose melphalan for conditioning (200 mg/m2). The toxicity of transplant as well as the outcome appears to be very similar to the younger patients. Patients with multiple myeloma should not be excluded from high dose therapy solely on the basis of their chronological age.

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.

Response to Tyrosine Kinase Inhibitor Therapy In Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Phase Chronic Myeloid Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3515-3515
Author(s):  
Ailsa Holroyd ◽  
Elizabeth Phillips ◽  
Richard Szydlo ◽  
David Marin ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Cell Transplantation ◽  
Research Funding ◽  
Blast Crisis ◽  
Disease Stage ◽  
Advanced Phase ◽  
Historical Group

Abstract Abstract 3515 With the advent of tyrosine kinase inhibitors (TKI), allogeneic stem cell transplantation (allo-SCT) is largely reserved for patients with CML who do not achieve durable cytogenetic responses to TKIs or patients with advanced phase (Adv) disease. Data relating to the outcome of transplant in Adv-CML is limited. We have allografted 43 patients (median age 40.8 yrs) for Adv phase disease who had received prior treatment with one or more TKI. The indications for allo-SCT included progression from CP to accelerated phase (AP) (n=16) or blast crisis (BC) (n=11) on TKI and presentation in accelerated phase (AP) (n=9) or blast crisis (BC) (n=7). The median duration of TKI therapy prior to transplantation was 5.5 months (range 1–51 months); 42 patients received imatinib, 9 received dasatinib (8 following imatinib failure), 2 received nilotinib (following imatinib and dasatinib failure). 35 patients were transplanted from HLA-identical siblings and 36 patients received myeloablative conditioning. The status at transplant was CP>1 in 17 patients, AP in 24, and BC in 2. In patients in whom CP was restored prior to transplant (n=17), this had been achieved using a TKI only in 6 and with combination chemotherapy in 11. There was no difference in disease-free survival (DFS) or overall survival (OS) between the TKI only group and the group that received chemotherapy in addition. Among the 43 patients in the TKI-treated cohort, 13 died without relapse, 3 from graft versus host disease (GVHD), 8 from sepsis, pneumonitis and multiorgan failure, and one each from graft failure and VOD. The estimated probabilities of non-relapse mortality (NRM) at 100 days and 1 year were 17.3% and 43.3%, Grade 2–4 acute GVHD was seen in 24% and extensive cGVHD in 54%. The estimated 1- and 3-year DFS rates were 23% and 16%. The 1 year and 3 year estimates of overall survival according to disease stage at allo-SCT were as follows: AP (54.2% and 50%), CP >1 (49.4% and 29.6%) and BC disease 0% and 0%. The impact of maximal disease stage was examined, documented as either AP (23/43 patients) or BP (20/43 patients) at any time prior to allo-SCT. The probability of 3 year OS for patients who were in AP at maximal disease stage was 61% compared to 33% of patients who had at one time been in BC (p=0.04). Post allo-SCT, patients were monitored for relapse by RQ-PCR. Eleven patients received TKIs, 5 for molecular relapse, 1 for cytogenetic relapse, 4 for hematological relapse and 1 for GvHD. Three of the 11 remain alive, 2 of whom received a TKI for molecular relapse.We compared the outcome of these 43 patients with that of 158 patients who were transplanted for Adv-CML but who had been treated before TKI became available. The disease status at time of transplant was AP (n=90), CP>1 (n=41) and BC (n=27). The two groups were matched for type of donor, conditioning regimens and time from diagnosis to transplant but the historical group were younger at allo-SCT with a median age of 33.3 yrs (p=0.001). There were no significant differences in the incidences of acute and chronic GvHD, NRM, DFS or OS between the two groups. The 1 year and 3 year estimates of OS for the historical cohort were 46.4% and 38.5% in AP, 53.7% and 24.3% for CP >1 and 7% and 0% in BC. For the total group of 201 patients the outcome of transplant defined as 3yr OS was 40.9% for AP 25.7% for CP>1 and 0% for BC. In conclusion, we found that patients receiving transplant for advanced phase disease after prior treatment with a TKI have similar outcomes to a historical group of advanced phase patients transplanted prior to the advent of TKI therapy. Our data strongly support the influence of disease stage in prediction of allo-SCT survival. Allo-SCT may be valuable for CML patients who have never progressed to BC. Overt BC is a predictor of poor allo-SCT outcome, so attempts should be made to restore CP prior to allo-SCT. Close monitoring of patients still classifiable as AP who are responding poorly to TKI should permit identification of those who may do well if offered allo-SCT before their disease has progressed further. Disclosures: Marin: Novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding.

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 The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4858-4858
Author(s):  
Federica SORA ◽  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age &gt;60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

scholarly journals Reduced Intensity Vs. Myeloablative Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with Myelodysplastic Syndrome: Long Term Follow-up of a Prospective Randomized EBMT Phase III Study (RICMAC-Trial)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1019-1019
Author(s):  
Nicolaus Kroeger ◽  
Simona Iacobelli ◽  
Linda Koster ◽  
Dietger Niederwieser ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Phase Iii ◽  
Long Term Follow Up

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. A higher risk of relapse after RIC was confirmed in a prospective BMT CTN study but the prospective randomized studies from the EBMT for MDS and sAML did not show a difference in outcome after 2 years (J Clin Oncol. 2017 Jul 1;35(19):2157-2164). Here we present a long term follow-up of the study after a median follow-up of 75 months (range 4-150 months). Methods Within the European Society of Blood and Marrow Transplantation (EBMT) we conducted a prospective, multicenter, open label, randomized phase III trial comparing 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, a total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1 : 1 ratio and stratified according to donor, age and blast count. Results In the first report (JCO 2017) the CI of NRM after 1 year was 17% (95% CI 8-26%) after RIC and 25% (95% CI 15-36%) after MAC (p = 0.29). The CI of relapse at 2 years was 17% (95% CI 8-26%) after RIC and 15% (95% CI 6-24%) after MAC (p = 0.6), resulting in a 2 year relapse-free and overall survival of 62% (95% CI 50-74%) and 76% (95% CI 66-87%) after RIC and 58% (95% CI 46-71%) and 63% (95% CI 51-75%) after MAC (p = 0.58 and p = 0.08, respectively). In the current follow-up study, all cases but one who were alive at last report could be updated. The median follow-up is now 75 months in the MAC and 72 months in the RIC arm. Since last follow-up =18 death occurred in both arm (MAC n=8, RIC n=10) 8 relapses (MAC n=4; RIC n=4) and 6 NRM (MAC n=2; RIC n=4). Second allogeneic stem cell transplantation was performed in 18 patients (n=10 in RIC and n=8 in MAC) due to graft failure (n=4) relapse (n=11) and others (n=3). The CI of chronic GvHD at 5 years was 65% (95% CI: 53-78) after RIC and 68% after MAC ((95% CI: 55-81; p = 0.70). At 5 years there was no difference in CI of NRM (22%, 95%CI: 12-32 vs 30% , 95%CI : 19-42, p=0.5) in CI of Relapse (22% , 95% CI: 12-32 vs18%, 95% CI: 8-28, p= 0.7), Relapse free- (57%, 95% CI: 44-69 vs51%, 95% CI: 39-64, p=0.8) and Overall survival (69%, 95% CI: 58-80 vs 53%, 95% CI: 40-65, p=0.15) between RIC and MAC, respectively. Conclusion This long term follow-up of the prospective randomized EBMT trial confirmed early results that RIC resulted in at least similar long term relapse-free and overall survival as MAC in patients with MDS or sAML. The trial was registered under ClinicalTrials.gov Identifier: NCT01203228. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Platzbecker:Celgene: Research Funding. Scheid:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria. Stelljes:MSD: Consultancy; Amgen: Honoraria; JAZZ: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Heim:Novartis: Research Funding. Bethge:Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding. Kobbe:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding.

scholarly journals Outcomes of Refractory and Relapsed Hodgkin Lymphoma With Autologous Stem-Cell Transplantation: A Single Institution Experience

2019 ◽  
pp. 1-6 ◽  
Author(s):  
Rabia Wali ◽  
Haleema Saeed ◽  
Naveed Patrus ◽  
Shehla Javed ◽  
Saadiya Javed Khan
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Retrospective Analysis ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease

PURPOSE Hodgkin lymphoma is the most common cancer in children, adolescents, and young adults. Overall survival is approximately 80% to 90%. A subset of these patients has refractory disease or experience disease relapse. Conventional salvage therapies and autologous stem-cell transplantation is usually considered the standard of care for these patients. Our analysis reports outcomes in these patients. PATIENTS AND METHODS After institutional review board approval, a retrospective analysis of patients with Hodgkin lymphoma who were up to 18 years of age and who had refractory or relapsed disease at Shaukat Khanum Memorial Cancer Hospital and Research Centre from September 2009 to December 2013 was performed. Patients who underwent high-dose chemotherapy followed by stem-cell rescue were included in this analysis. RESULTS A total of 567 patients with Hodgkin lymphoma registered at the hospital. Sixty of the patients (10.6%) had either primary progressive or refractory disease or relapse after finishing with first-line chemotherapy. High-dose chemotherapy followed by stem cell was administered to 25 of these patients (42%). Thirteen patients (40%) had progressive disease (PD), five (22%) had early relapse, and seven (38%) had late relapse. A number of salvage regimens were used, including etoposide, prednisolone, ifosfamide, and cisplatin; dexamethasone, cytarabine, and carboplatin; and gemcitabine plus vinorelbine. Re-evaluation was performed before taking patients to a high dose, and it showed complete response in 17 patients (68%), partial response in six patients (24%), and PD in two patients (8%). Twenty-one patients (84%) are in remission after transplantation, with two patients (8%) having died as a result of disease progression and two patients (2%) having relapsed after treatment. Overall survival is 92% at 4 years, with event-free survival of 80% at 4 years. CONCLUSION Our retrospective analysis shows good outcomes in patients who had PD or refractory disease. Disease response before transplantation is important in predicting outcomes.

Development of a Frailty Score for Older Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1775-1775
Author(s):  
Barbara Deschler ◽  
Gabriele Ihorst ◽  
Uwe Platzbecker ◽  
Ulrich Germing ◽  
Michael Lübbert
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Activities Of Daily Living ◽  
Cell Transplantation ◽  
Daily Living ◽  
Older Patients ◽  
Treatment Allocation ◽  
Frailty Score

Abstract Abstract 1775 Poster Board I-801 Introduction Treatment options in older patients (pts) with MDS/AML range from best supportive care (BSC) to intensive chemotherapy/hematopoietic stem cell transplantation (IC/HCT), with low-dose chemotherapy or novel non-intensive agents (e.g. hypomethylating agents; HA) as alternatives. Due to frequent age-related physical and/or mental impairments, intensive treatment is not always feasible. As the basis for treatment decision-making is not well defined, the generation of comprehensive assessments of age-specific functional and quality of life (QOL)-aspects in addition to disease-specific risk factor definition therefore is urgently needed. Geriatric Assessment (GA) is expected to offer rational support in this process. Patients and Methods Since January 2004, we have prospectively evaluated the prognostic impact of GA on overall survival (OS) in 195 consecutive pts ≥60 years (yrs) with AML (n=132) or MDS (n=63) in three participating centers, receiving either BSC or HA+BSC or IC/HCT. Of the pts receiving non-intensive treatment, 50% had MDS. GA included eight instruments evaluating QOL, activities of daily living, depression, mental functioning, mobility, comorbidities and performance status (PS). In addition, disease- and patient-specific laboratory parameters were obtained. Results Median age of pts was 71 yrs (range: 60-87 yrs). The primary treatment allocation was BSC in 47 pts (median age: 75 yrs); HA+BSC in 66 pts (74 yrs); IC/HCT in 75 pts (68 yrs). 62% of IC/HCT pts received a matched related/unrelated stem cell transplantation. Application of age-specific tests at the different study centers was readily feasible. The initial multidimensional GA was associated with treatment allocation, age, hematological and functional parameters and treatment outcome. Multivariate analyses revealed impairments in activities of daily living (ADL: Barthel Test, HR: 2.22) and fatigue (measured by EORTC QLQ-C30; HR: 1.68) as significant prognostic parameters for overall survival. Both risk factors were combined to construct a simple risk score for survival. Conducting a Cox regression model with established risk factors, a high risk frailty score in the entire pt population was associated with an elevated HR of 4.17 (p<0.0001), while adverse cytogenetics (AML), blasts >20% and comorbidities >1 proved to be independently associated with HRs of 2.491 (p=0.0001), 2.756 (p=0.0005) and 1.495 (p=0.1281). When this score was applied to pts receiving sole BSC or HA+BSC, highly significant differences in OS could be demonstrated, with p=0.0035 and p<0.0001, respectively. Conclusions Our data demonstrate that GA is a useful and objective tool in the in-depth evaluation process prior to treatment allocation in elderly patients with MDS/AML. A simple prognostic score based solely on ADL and fatigue to predict outcome of patients treated non-intensively has been established. Validation in independent cohorts appears warranted. Disclosures No relevant conflicts of interest to declare.

Concordance Between the Serum Levels of Interleukin-6, Microrna-21, and the Severity of Subjective Symptoms of Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2953-2953
Author(s):  
Bang-Ning Lee ◽  
Sergio Giralt ◽  
Evan Cohen ◽  
Matthew Galland ◽  
Tiffany Lafortune ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Inflammatory Cytokines ◽  
Induction Therapy ◽  
Inflammatory Mediators ◽  
Serum Levels ◽  
Younger Patients ◽  
Tnf Α ◽  
The Mean

Abstract Abstract 2953 Multiple myeloma (MM) is an incurable cancer characterized by the clonal proliferation of plasma cells within the bone marrow. Current treatment for most patients with newly diagnosed MM includes induction therapy (typically dexamethasone plus thalidomide or bortezomib for patients eligible for autologous stem cell transplantation [AuSCT], melphalan and prednisone, with or without thalidomide, for those ineligible for transplantation), followed by consolidation with high-dose melphalan and AuSCT for transplant-eligible patients, and finally maintenance therapy. Intensive induction therapy and AuSCT produce superior outcomes in younger patients (<60 years) with Stage II/III MM when compared with patients receiving standard induction therapy. Older patients undergoing AuSCT are more likely to experience physical, gastrointestinal and affective symptoms than younger patients. Cancer and cancer treatment related symptoms involve the actions of proinflammatory cytokines. One of the actions of inflammatory cytokines is to regulate microRNA (miR), small non-coding RNA that can regulate the expression of inflammatory mediators. Therefore, we investigated the relationship between the serum levels of inflammatory mediators (cytokines and relevant miR) and the severity of the self-reported symptoms in MM patients undergoing AuSCT. This ongoing prospective study consists of sixteen elderly (64.6 yrs ± 6.9 yrs) subjects with stage II/III MM, 10 men and 6 women;12 Caucasian, 3 Hispanic, and 1 African-American. Sera were obtained prior to AuSCT, then biweekly for the first 4 weeks, and at 3 and 6 months to measure levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α) by Luminex bead array assay and circulating miR-21 and miR-146a by real-time PCR. Self-reported symptoms were assessed by the MD Anderson Symptom Inventory - multiple myeloma module (MDASI-MM). Non-parametric Spearman's test determined the correlation between the above biomarkers and the symptom scores. Several self-reported symptoms peaked around nadir (+7 days) including fatigue, poor appetite, drowsiness, nausea, and dry mouth. Whereas IL-6 and IL-8 levels peaked around nadir, IL-1RA and TNF-α levels dropped by nadir and then recovered by 2–4 weeks post AuSCT. There were significantly positive correlations between the serum level of IL-6 and other inflammatory cytokines IL-1RA, IL-8, and TNF-a across the time points of sampling. In addition, serum levels of IL-6 and TNF-a statistically positively correlated with miR-21. Serum IL-6 and IL-10 levels were positively correlated with the mean score of MDASI core symptoms and of MM-related symptoms; whereas the level of miR-21, and not miR-146a, was linearly positively correlated with the mean scores of MDASI-MM symptoms. To our knowledge, this is the first study to report the concordance between serum levels of IL-6 and miR-21, and symptom burden of MM patients. These results suggest that targeting miR involved in cytokine deregulation and disease relapse may provide survival benefit for patients undergoing AuSCT. Disclosures: Giralt: Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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